Clinical trial NCT02494921
Conditions: Prostate Cancer
Keywords: Metastatic Castration-Resistant
Sponsor: Rahul Aggarwal
Start date: 2015-11-20; Completion date: 2021-07-30
Enrollment: 43 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase Ib/II open label clinical trial in patients with metastatic castration resistant prostate cancer. The objective of the phase Ib portion of the study is to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of docetaxel (75 mg/m2 IV q21 days) and prednisone (5mg orally BID) in combination with ribociclib in escalating oral daily doses in patients with metastatic castrate resistant prostate cancer (mCRPC) with prior resistance to abiraterone and/or enzalutamide who have not undergone prior chemotherapy for metastatic disease. Up to three cohorts will be enrolled to determine the MTD and DLT profile of this combination during Phase 1b. Dose escalation will follow the standard 3+3 design. The dosing schedule is being chosen to allow patients to be exposed to the most efficacious dosing schedule of docetaxel (75 mg/m2 every 3 weeks). If there is excess toxicity observed with the treatment combination at the first dose level (dose level I), an alternative dosing schema may be pursued with weekly docetaxel treatment (35 mg/m2 weekly), which has demonstrated activity in mCRPC and decreased risk of cytopenias compared with every 3 week dosing schedule.

The Phase II portion (N = 29) of the study is a single arm, two stage, open-label study of ribociclib (dosed at the RP2D) in combination with docetaxel and prednisone to determine the efficacy and further define the safety of the treatment combination. Patients will be treated with the combination of ribociclib plus docetaxel + prednisone for up to 9 cycles. If there is no evidence of radiographic or clinical disease progression after 9 cycles of protocol therapy, patients may continue on single agent maintenance ribociclib until the time of disease progression. Patients will have the option of starting maintenance ribociclib after 6 cycles of docetaxel if stable disease or better on re-staging scans. The dose of ribociclib used during maintenance will be the same dose as that immediately preceding cessation of docetaxel treatment.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the safety profile, maximally tolerated dose (MTD), and recommended phase 2 dose of ribociclib in combination with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). (Phase IB) II. To determine the 6-month radiographic progression-free survival rate with the combination of ribociclib, docetaxel, and prednisone in patients with mCRPC. (Phase 2)

SECONDARY OBJECTIVES:

I. To determine the median radiographic progression-free survival with the combination of ribociclib, docetaxel, and prednisone in patients with mCRPC.

II. To determine the objective response rate and median duration of response among patients with measurable disease at baseline.

III. To determine the prostate-specific antigen (PSA) response proportion and time to PSA progression.

IV. To characterize the safety profile of ribociclib in combination with docetaxel.

V. To determine if there is evidence of drug-drug interaction between docetaxel + prednisone with ribociclib.

EXPLORATORY OBJECTIVES:

I. To determine whether baseline or percent change from baseline in gallium citrate uptake on positron emission tomography (PET) scan is associated with clinical outcomes. (For University of California San Francisco (USCF) Patients Only) II. To determine whether genomic assessment of MYC pathway activation (MYC amplification or overexpression, Rb1 deletion, cyclin D/E and CDK 4/6 overexpression) assessed within metastatic tumor tissue, circulating tumor cells (CTCs), and/or cell-free circulating tumor deoxyribonucleic acid (ctDNA) is predictive of clinical outcomes with the combination of ribociclib plus docetaxel.

III. To determine whether MYC activation score as determined by validated expression signature can distinguish those with and without clinical benefit with ribociclib in combination with docetaxel.

IV. To use an unbiased approach with integration of clinical, genomic, and proteomic data (differential pathway signature correlation; DiPSC) to define a signature associated with response to taxane + CDK4/6 inhibition in mCRPC.

OUTLINE: This is a phase Ib, dose-escalation study of ribociclib followed by a phase II study.

Patients receive docetaxel intravenously (IV) over 1 hour on day 1 or on days 1 and 8, prednisone orally (PO) twice daily (BID) on days 1-21, and ribociclib PO once daily (QD) on days 1-4, and 8-15. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or better on re-staging scans after 6 cycles and patients without radiographic or clinical disease progression after 9 cycles of treatment may continue on single agent maintenance ribociclib PO QD on days 1-14 of every 21 day cycle in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every three months.

Arms: arm 1: The starting cohort dose level (1) for docetaxel will be 75 mg/m2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level 1 is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level 1A of 60mg/m2 docetaxel. arm 2: Participants in Phase 2 will receive the Recommended Phase 2 Dose for docetaxel and ribociclib
Interventions: intervention 1: Docetaxel-PNP intervention 2: Ribociclib intervention 3: Prednisone intervention 4: Filgrastim
Intervention descriptions: intervention 1: Given IV intervention 2: Given Orally intervention 3: Given Orally intervention 4: Given IV

Protocol documents:
Prot_SAP_000.pdf: 
Proprietary and Confidential
The information in this document is considered privileged and confidential, and may not be disclosed to others except 
to the extent necessary to obtain Institutional Review Board approval and informed consent, or as required by 
Federal and State laws. Persons to whom this information is disclosed should be informed that this information is 
privileged and confidential and that it should not be further disclosed.
 A Phase 1b/2 Study of the Oral CDK4/6 Inhibitor LEE011 (Ribociclib) in Combination with Docetaxel plus 
Prednisone in Metastatic Castration Resistant Prostate Cancer
UCSF Protocol Number: 145515 
Version Date: February 4th, 2019 
Version Number: 5.0
IND Number: 125490
IST Number: CLEE011XUS07T
Principal Investigator:
Rahul Aggarwal, M.D.
UCSF Helen Diller Family Comprehensive Cancer Center 
 
 Eric Small, M.D. 
Lawrence Fong, M.D.
Jack Youngren, Ph.D. 
Pamela Paris, Ph.D. 
Josh Stuart, Ph.D.
Felix Feng, M.D.
Co-Investigators:
Terence Friedlander, M.D. 
Amy M. Lin, M.D. 
Tammy Rodvelt, N.P.
Correlative Science:
Robert Baertsch, Ph.D. 
Henry VanBrocklin, Ph.D. 
Michael Evans, Ph.D.
Biostatistician:
Li Zhang, Ph.D.
Revision History
Version 4.0
10-05-2018
Version 5.0
02/04/2019
Version 3.0
03-06-2017
Version 2.5
04-09-2016
Version 2.4
04-22-2015
Version 2.3
03-19-2015
Version 2.1
01-19-2015
Version 2.0
11-13-2014
NCT# 02494921


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Protocol Signature Page
Protocol No.: 145515                                                                                 Version Date: February 4th, 
2019
1.
I agree to follow this protocol version as approved by the UCSF Protocol Review Committee (PRC), 
Investigational Review Board (IRB), and Data Safety Monitoring Committee (DSMC).
2.
I will conduct the study in accordance with applicable IRB requirements, Federal regulations, and 
state and local laws to maintain the protection of the rights and welfare of study participants.
3.
I certify that I, and the study staff, have received the requisite training to conduct this research 
protocol.
4.
I have read and understand the information in the Investigators’ Brochure (or Manufacturer’s 
Brochure) regarding the risks and potential benefits. I agree to conduct the protocol in accordance 
with Good Clinical Practices (ICH-GCP), the applicable ethical principles, the Statement of 
Investigator (Form FDA 1572), and with local regulatory requirements. In accordance with the FDA 
Modernization Act, I will ensure the registration of the trial on the www.clinicaltrials.gov website.
5.
I agree to maintain adequate and accurate records in accordance with IRB policies, Federal, state and 
local laws and regulations.
UCSF Principal Investigator / Study Chair
Printed Name
Signature
Date


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Title
A Phase 1b/2 Study of the Oral CDK4/6 Inhibitor LEE011 (Ribociclib) in Combination with 
Docetaxel Plus Prednisone in Metastatic Castration Resistant Prostate Cancer
Patient 
Population
Patients with metastatic castration resistant prostate cancer and prior resistance to abiraterone, 
enzalutamide, ARN-509, or the combination.
Rationale 
for Study
Prostate cancer is the second leading cause of cancer death in the United States.1 Although most 
advanced prostate cancers are initially responsive to androgen ablation therapy, eventually all of
these tumors become refractory to androgen deprivation. In the metastatic castration-resistant 
setting, the widespread introduction of more potent and complete androgen signaling inhibition 
with abiraterone and enzalutamide has increasingly shifted the landscape of advanced prostate 
cancer towards an aggressive phenotype with frequent histopathological evidence of 
neuroendocrine differentiation.2 The clinical features of this lethal subset of disease are 
characterized by frequent visceral and widespread osseous metastases and limited responsiveness 
to androgen signaling inhibition. The current standard of care in this setting remains docetaxel- 
based chemotherapy, which provides a modest improvement in survival outcomes compared  
with older chemotherapy regimens.3 Prior efforts to combine targeted therapies with docetaxel to 
improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) have not met 
with success.4-11 This may be in part be related to lack of biomarker enrichment to select the 
patients with tumors most dependent on the drug target to guide rationale clinical trial design.
Emerging studies implicate up-regulation of cell cycle progression via MYC activation as a key 
driver of the increased proliferative activity observed with progression to an aggressive 
phenotypic mCRPC. Pre-clinical studies have demonstrated that cyclin dependent kinases 4/6 
(CDK 4/6) are direct transcriptional targets of MYC that mediate accelerated progression  
through the cell cycle to drive prostate tumor growth.12 Inhibition of CDK 4/6 in a prostate  
cancer cell line resistant to enzalutamide, has demonstrated potent arrest of cellular 
proliferation.13 Prior pre-clinical data in other MYC-driven tumor subtypes (triple negative breast 
cancer) indicate synthetic lethality with CDK inhibition in combination with taxane-based 
chemotherapy14, and an ongoing phase 1 study of CDK inhibition in combination with paclitaxel 
suggests the combination is tolerable.
The current study is designed to determine the MTD of ribociclib, a potent CDK 4/6 inhibitor) in 
combination with docetaxel, and in the phase 2 portion of the study, to assess its efficacy in 
mCRPC patients with prior resistant to abiraterone and/or enzalutamide. The integration 
correlative biomarker studies, including the use of tumor and “liquid” biopsies to identify Rb1 
status and presence of MYC pathway activation, along with metabolic imaging of MYC 
transcriptional activity, may potentially identify those tumors most ‘addicted’ to MYC signaling 
and therefore the most likely to achieve therapeutic benefit with inhibition of CDK 4/6, a key 
downstream mediator of MYC-driven up-regulation of cell cycle progression.
Primary 
Objectives
Phase 1b:
To determine the safety profile, maximally tolerated dose (MTD), and recommended  phase 
2 dose of ribociclib in combination with docetaxel plus prednisone in patients with mCRPC.
Phase 2:
To determine the 6-month radiographic progression-free survival rate with the 
combination of ribociclib, docetaxel, and prednisone in patients with  mCRPC.


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Secondary 
Objectives
 
To determine the median radiographic progression-free survival with the combination of 
ribociclib, docetaxel, and prednisone in patients with mCRPC.

To determine the objective response rate and median duration of response among patients 
with measurable disease at baseline.

To determine the PSA response proportion and time to PSA progression.

To characterize the safety profile of ribociclib in combination with docetaxel.

To determine if there is evidence of drug-drug interaction between docetaxel + 
prednisone with ribociclib.
Correlative 
Objectives

To determine whether baseline or percent change from baseline in gallium citrate uptake 
on PET scan is associated with clinical outcomes (Optional - UCSF Patients Only).

To determine whether genomic assessment of MYC pathway activation (MYC 
amplification or overexpression, Rb1 deletion, cyclin D/E and CDK 4/6 overexpression) 
assessed within metastatic tumor tissue, circulating tumor cells, and/or cell-free 
circulating tumor DNA is predictive of clinical outcomes with the combination of 
ribociclib plus docetaxel.

To determine whether MYC activation score as determined by validated expression 
signature can distinguish those with and without clinical benefit with ribociclib in 
combination with docetaxel.

To use an unbiased approach with integration of clinical, genomic, and proteomic data 
(Differential Pathway Signature Correlation; DiPSC) to define a signature associated 
with response to taxane + CDK4/6 inhibition in mCRPC.


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1
BACKGROUND
1.1
Overall Study Rationale
Prostate cancer is the second leading cause of cancer death in the United States.1 Although most advanced 
prostate cancers are initially responsive to androgen ablation therapy, eventually all of these tumors 
become refractory to androgen deprivation. In the metastatic castration-resistant setting, the widespread 
introduction of more potent and complete androgen signaling inhibition with abiraterone and 
enzalutamide has increasingly shifted the landscape of advanced prostate cancer towards an aggressive 
phenotype with frequent histopathological evidence of neuroendocrine differentiation.2 The clinical 
features of this lethal subset of disease are characterized by frequent visceral and widespread osseous 
metastases and limited responsiveness to androgen signaling inhibition. The current standard of care in 
this setting remains docetaxel-based chemotherapy, which provides a modest improvement in survival 
outcomes compared with older chemotherapy regimens.3 Prior efforts to combine targeted therapies with 
docetaxel to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) have not 
met with success.4-11  This may in part be related to lack of biomarker enrichment to select the patients 
with tumors most dependent on the drug target to guide rationale clinical trial design.
Emerging studies implicate up-regulation of cell cycle progression via MYC activation as a key driver of 
the increased proliferative activity observed with progression to an aggressive phenotypic mCRPC. Pre- 
clinical studies have demonstrated that cyclin dependent kinases 4/6 (CDK 4/6) are direct transcriptional 
targets of MYC that mediate accelerated progression through the cell cycle to drive prostate tumor 
growth.12 Inhibition of CDK 4/6 in a prostate cancer cell line resistant to enzalutamide, has demonstrated 
potent arrest of cellular proliferation.13 Prior pre-clinical data in other MYC-driven tumor subtypes (triple 
negative breast cancer) indicate synthetic lethality with CDK inhibition in combination with taxane-based 
chemotherapy14, and an ongoing phase 1 study of CDK inhibition in combination with paclitaxel suggests 
the combination is tolerable.
The current study is designed to determine the MTD of ribociclib, a potent CDK 4/6 inhibitor) in 
combination with docetaxel, and in the phase 2 portion of the study, to assess it's efficacy in mCRPC 
patients with prior resistance to abiraterone and/or enzalutamide. The integration correlative biomarker 
studies, including the use of tumor and “liquid” biopsies to identify Rb1 status and presence of MYC 
pathway activation, along with metabolic imaging of MYC transcriptional activity, may potentially 
identify those tumors most ‘addicted’ to MYC signaling and therefore the most likely to achieve 
therapeutic benefit with inhibition of CDK 4/6, a key downstream mediator of MYC-driven up-regulation 
of cell cycle progression.
1.2
Rationale for Targeting Cell Cycle Progression in Advanced Prostate Cancer
Up-regulation of cell cycle progression is a frequent molecular driver of aggressive phenotype metastatic 
CRPC. Loss of the tumor suppressor PTEN is observed in 50-90% of CRPC tumors, leading to 
downstream activation of effectors of the PI3K pathway, including cyclin D, a key driver of G1 to S 
phase cell cycle progression.15 Transdifferentiation towards a neuroendocrine phenotype has recently been 
molecularly characterized as an MYCN oncogene-driven variant in both pre-clinical models and patient- 
derived cancer tissue.16 The discovery of MYC overexpression in treatment-emergent NEPC has direct 
implications for targeting the cyclin-dependent kinase (CDK) pathway in this disease setting, given the 
direct transcriptional regulation of CDK 4/6 via MYC activation. A recently reported PTEN-knockout 
transgenic model of prostate cancer identified MYC overexpression upregulation as a key driver of tumor 
progression.15  In a landmark translational study of the prostate cancer genome, 74% of human CRPC 
tissue samples displayed alteration of Rb signaling, with overactivation of CDK2 in 21% of cases and 
Rb1 loss in 37% of cases.16 In a previous study of MDV3100-resistant cancer cell lines, gene set


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enrichment analysis identified significant up-regulation of genes involved in cell cycle progression and 
E2F1 activation.13 Most contemporarily, ours and others data indicates progressive enrichment of MYC 
amplification as a driver of prostate cancer progression, with amplification detected in 16% of primary 
prostate adenocarcinomas in the TCGA database, ~ 25-30% of pre-abiraterone/enzalutamide mCRPC 
tumors, and over 80% of abiraterone-resistant mCRPC tumors from the ongoing UCSF mCRPC biopsy 
program (preliminary data, unpublished, CC#125519).
The application of CDK inhibitors has 
shown preliminary evidence of 
substantial anti-tumor activity in prostate 
cancer models, in particular those with 
androgen-independent growth upon 
resistance to androgen signaling 
inhibitors. In a panel of bicalutamide- 
resistant, androgen-independent prostate 
cancer cell lines, CDK2 inhibition was 
able to restore sensitivity with a potency 
that was comparable to that of LNCaP 
androgen-sensitive cell lines.17 More 
recently, CDK 4/6 inhibitors including 
ribociclib have been shown to have 
significant anti-proliferative effects in 
MDV3100 (enzalutamide)-resistant 
cancer cell lines bearing either mutant
Figure 1. Ribociclib significantly inhibits colony proliferation in 
the 22Rv1 enzalutamide (MDV) and bicalutamide (bic)-resistant 
prostate cancer cell line. Figure from Korpal M, et al. Cancer 
Discovery 2013;3(9):1030-1043.
F876L mutant- or wild type androgen receptor13  (Figure 1). The anti-tumor activity of CDK inhibitors 
has additionally been demonstrated in other MYC-driven cancers. Synthetic lethality with CDK inhibition
was demonstrated in multiple triple negative breast cancer lines which demonstrate up-regulated C-MYC 
signaling.14 Prior clinical studies with cell cycle inhibitors in mCRPC, include flavopiridol, have 
demonstrated modest activity18; however these agents were neither potent nor selective inhibitors of CDK 
4/6. It is hypothesized that potent CDK inhibition with ribociclib will have substantial additive or 
synergistic activity with docetaxel in mCRPC.
1.3
Rationale for Combination of CDK 4/6 Inhibitor With Taxane Chemotherapy
Taxane-based chemotherapy and CDK inhibitors have demonstrated synergistic activity in multiple 
independent studies, which may be related to blockade of cell cycle progression at separate phases of the 
cell cycle (M and G1 S phases respectively). In vitro studies have demonstrated synergy when cell cycle 
inhibitors like flavopiridol and purvalanol are administered with paclitaxel and docetaxel.14 Recently, the 
Goga lab at UCSF has demonstrated synergistic activity in TNBC cell lines (BT549, MDA-MB-231, 
HCC1143) treated with dinaciclib and paclitaxel therapy.14 In an ovarian cancer xenograft model, co- 
administration of docetaxel and dinaciclib demonstrated synergistic activity compared to either agent 
given alone. Similar synergistic activity with taxanes has been demonstrated with other CDK-inhibitors 
including flavopiridol, NU6410, and purvalonol. A phase 1b study of dinaciclib in combination with 
weekly paclitaxel (NCT01676753) being conducted at UCSF has demonstrated preliminary evidence of 
an acceptable safety profile with efficacy analyses ongoing. The above findings, coupled with the fact that 
docetaxel-based chemotherapy remains the standard of care for metastatic CRPC with aggressive 
phenotypic features and/or prior resistance to androgen signaling inhibition, provide a strong rationale to 
pursue the combination of CDK4/6 inhibition in combination with docetaxel in mCRPC.


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1.4
Summary of Ribociclib Pre-Clinical and Clinical Safety, PK, and Efficacy Data
In vitro Pharmacology:
Ribociclib inhibits the CDK4/CCND1 and CDK6/cyclin-D3 enzyme complexes with concentration 
resulting in 50% inhibition (IC50) values of 0.01 and 0.039 μM in biochemical assays, respectively. In 
Jeko-1 cells, the compound inhibits CDK4/6-dependent pRb phosphorylation with an average IC50 of
0.06 μM. Consistent with the observed inhibition of pRb phosphorylation, ribociclib also inhibited G1 to 
S phase cell cycle progression in Jeko-1 cells as judged by both the inhibition of bromodeoxyuridine 
(BrdU) uptake (IC50 of 0.1 μM) and fluorescence activated cell sorting (FACS) analysis (half-maximal 
increase in cells in G1 at 0.11 μM).
The effect of ribociclib on pRb phosphorylation, BrdU uptake and cell cycle progression has been 
assessed in > 40 cell lines derived from hematological, esophageal, liposarcoma and breast cancers. In 
pRb+ cell lines ribociclib inhibits pRb phosphorylation with a median IC50 value of 0.275 μM (range:
0.06 to 8.8 μM). Similarly, ribociclib interferes with G1 to S phase cell cycle progression in these cells as 
determined by either BrdU uptake or FACS analysis with a median IC50 value of 0.46 μM.
In vivo Pharmacology:
Ribociclib was well-tolerated in mice and rats with body weight loss not exceeding 12.5% at doses up to 
250 mg/kg, qd, po. No significant changes in blood chemistry readouts were observed after 28 days of 
dosing. However, myelosuppression was observed and correlated with pRb phosphorylation inhibition.
Treatment with ribociclib resulted in tumor regression in the Jeko-1 MCL xenograft model at doses 
greater than or equal to 75 mg/kg, qd, po. In vivo pharmacokinetic (PK)/PD studies demonstrated dose- 
related inhibition of pRb phosphorylation in tumors, with continuous dosing over at least 3-5 days being 
required to achieve optimal target inhibition. In male nude rats a PK/PD/efficacy study indicated that 
plasma levels corresponding to approximately 0.5 - 4 μM over a 24 h dose interval are sufficient to obtain 
near complete inhibition of pRb phosphorylation and complete regression in the Jeko-1 MCL xenograft 
model.
Non-clinical Safety and Toxicology:
In vivo cardiac safety studies demonstrated a signal for QT prolongation with the potential to induce 
incidences of premature ventricular contractions (PVCs) at higher exposure levels. The effects of 
ribociclib on the bone marrow (hypocellularity), lymphoid system (lymphoid depletion), intestinal 
mucosa (atrophy), skin (atrophy), bone (decreased bone formation) and testes (atrophy) are considered to 
be related to the pharmacological inhibition of cell replication in these tissues due to CDK4/6 inhibition. 
An increased number of ovarian corpora lutea was observed in a single female dog at the highest dose 
tested (20 mg/kg/day) and this effect could also be related to the pharmacology of ribociclib (arrest of 
estrous cycle). The liver, bile system and gall bladder (proliferative changes, cholestasis, sand-like 
gallbladder calculi and inspissated bile) were identified as additional target organs of toxicity which are 
not likely related to the primary pharmacology of ribociclib. Inflammatory changes in the lungs of dogs 
were considered secondary to aspiration of test-article and are indicative of the irritant potential of the 
formulated test-article in the respiratory tract. Correlating hematological and/or biochemistry changes 
were seen for the effects described in the bone marrow, lymphoid system and liver. In rats, the changes 
seen in the bone marrow and hematology demonstrated a clear tendency towards reversibility. All other 
findings fully reversed. In dogs, the changes seen in the testes and lungs demonstrated a clear trend


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towards reversibility and all the other changes were fully reversible. However, it can be expected that 
after a prolonged recovery time all findings would have totally reversed.
Reproductive studies have demonstrated ribociclib induced embryotoxicity and fetotoxicity in rats and 
rabbits and teratogenicity in rabbits.
Non-clinical Pharmacokinetics and Metabolism:
Following intravenous [i.v.] dosing, ribociclib showed high CL in the mouse, rat, dog and monkey 
compared to hepatic blood flow. The volume of distribution at steady-state was large across species and 
the terminal elimination half-life (T1/2) was moderate in rodents and monkey (~2 to 5 h) and longer in 
dog (18 h). After oral administration to male rats, 48 to 84% of a radiolabeled dose of ribociclib was 
absorbed. Bioavailability was low to moderate in rat (10 to 65%) and cynomolgus monkey (10 to 23%), 
and moderate in mouse (65%) and dog (64%). Following oral administration, Tmax occurred between 2 
to 4 h across species. Gender-dependent toxicokinetics were observed in rats with higher exposure to 
ribociclib in males as compared to females and with higher exposure to the metabolite, LEQ803.
Plasma protein binding was moderate and showed no major concentration dependency. Free fraction in 
plasma ranged from 20 to 32%.
LEQ803 (N-demethylation) was a prominent metabolite found in rat, monkey and human hepatocytes, 
and the only metabolite formed in dog hepatocytes. This metabolite retains some pharmacologic activity 
and interacts with hERG channels in vitro. Traces of two potential unique human metabolites were 
detected in hepatocytes. In mice, rats, monkey and human, GSH-adducts were detected however these 
were not seen in plasma or excreta from the rat ADME study. Results from the ADME (male rats) study 
showed that 3H-components were predominantly excreted with bile (61.4% of dose). Minor urinary 
excretion was observed (5.44% of dose after p.o. to 10.1% of dose after i.v.). The majority of the 
administered dose (87.3%) was excreted within 24 h via urine, feces (enteric secretion) and bile.
Drug-drug interaction: Oxidative metabolism of ribociclib is dominated by CYP3A4 with a minor 
contribution of about 20% by flavin containing monooxygenase-3 (FMO3). ribociclib is a low-affinity 
substrate of P-gp (MDR1). ribociclib is a time-dependent CYP3A4 inhibitor (KI = 5 μM, kinact = 0.0245 
min-1) and a reversible inhibitor of CYP1A2 (Ki = 16 μM). No PXR-mediated CYP3A4 induction was 
observed. ribociclib was found to inhibit MDR1 (IC50 = 143 μM), MXR (IC50 = 24 μM), and human 
BSEP (IC50 = 4.7 μM), but not rat or dog BSEP. The elimination of ribociclib may potentially be 
affected by co-administered drugs that inhibit or induce CYP3A4. ribociclib may inhibit CYP3A4, 
CYP1A2, BSEP, and MXR depending on the dose and ribociclib concentrations achieved in vivo.
Clinical Studies:
In single agent trials, a total of 179 patients have been treated: 132 in study CLEE011X2101 (in a 
Caucasian population, including 85 in the dose escalation), 15 in CLEE011X1101 (in Japanese patients, 
all in the dose escalation) and 32 in CLEE011X2102 (in patients under the age of 21 years, all in the dose 
escalation). A total of 18 patients presented toxicities meeting the dose limiting toxicity (DLT) criteria (10 
in CLEE011X2101, 4 in CLEE011X1101 and 4 in CLEE011X2102): these consisted of Grade 3 
stomatitis, Grade 3 pulmonary embolism, Grade 3 hyponatremia, prolonged Grade 3/4 neutropenia (x2), 
prolonged Grade 2 elevated creatinine, Grade 4 thrombocytopenia (x5), Grade 3 asymptomatic QTcF 
prolongation with Grade 3 neutropenia, Grade 4 febrile neutropenia, Grade 3 febrile neutropenia (x2), 
Grade 3 electrocardiogram QT prolonged, Grade 3 fatigue, and Grade 3 asymptomatic QTcF prolongation 
with grade 4 neutropenia.


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The maximum tolerated dose (MTD) and recommended dose for expansion (RDE) from study 
CLEE011X2101 were declared as 900 mg qd and 600 mg qd on a 3 weeks on/1 week off schedule, 
respectively. At the RDE, the most common (in at least 2 patients) adverse events (AEs) related to study 
treatment were (all grades, Grade 3/4): neutropenia (46.3%, 28.4%), leukopenia (46.3%, 19.4%), nausea
(44.8%, 1.5%), thrombocytopenia (34.3%, 9%), fatigue (32.8%, 3%), anaemia (28.4%, 3%), diarrhoea
(26.9%, 3%), lymphopenia (22.4%, 17.9%), electrocardiogram QT prolonged (9%, 0%), hyponatremia
(3%, 1.5%), and febrile neutropenia (1.5%, 1.5%). Asymptomatic grade 2 QTc prolongation was 
observed with increasing frequency starting at 600 mg with grade 3 prolongation in 2 patients (3%). The 
majority of all reported adverse events were mild or moderate (grade 1-2) and reversible. There have been 
no reported deaths related to single agent ribociclib.
Paired skin biopsies from 55 patients treated with ribociclib at doses ranging from 50 to 900 mg and 
paired tumor biopsies from 20 patients (16 patients at 600 mg, 2 patients at 900 mg, and 1 patient each at 
70 and 750 mg) were assessed for changes in Ki67 and pRb levels. Preliminary results indicate the 
following: in skin biopsies, reductions in Ki67 from baseline were observed across all dose levels with a 
more consistent trend from 400 mg onwards; in tumor biopsies, reductions in Ki67 from baseline were 
observed in 18/20 patients; however, limited samples and varied tumor types prevent conclusions about 
any dose-response relationship from being drawn. Changes in pRb were not significant or consistent in 
either skin or tumor samples, possibly due to varied tumor types.
Preliminary data for clinical activity from study CLEE011X2101 show that out of 114 evaluable patients, 
3 partial responses were seen at the 600 mg qd dose level: one in a BRAF/NRAS wild type, CCDN1 
amplified melanoma patient, one in a CDKN2A loss head and neck acinar carcinoma patient, and one in 
an ER+/HER2-, PIK3CA mutant, CCDN1 amplified breast cancer.
Following oral dosing, ribociclib was rapidly absorbed with median Tmax ranging from 1 to 5 hours. 
ribociclib plasma exposure exhibited slightly over-proportional increases in exposure across the dose 
range tested (50 to 1200 mg), with no clear evidence of time-dependent auto-inhibition of its clearance 
mediated by CYP3A4. Steady-state was generally reached by Day 8 and the mean effective T1/2 based on 
accumulation ratio (i.e., T1/2,acc) ranged from 15.9 to 32.6 hours across the dose range tested. The 
accumulation ratio based on AUC obtained in a dosing interval (Racc) across the studied doses ranged 
from 1.55 to 2.52.
The MTD of single agent ribociclib is 900 mg qd with a 3 weeks on/1 week off schedule. The RP2D for 
future development of single agent ribociclib dosing is 600 mg qd with a 3 weeks on/1 week off schedule 
which has an acceptable safety profile, lower risk for QT prolongation, adequate exposures, and 
preliminary evidence of clinical activity.
1.5
Summary of Docetaxel Mechanism of Action, Efficacy, Safety and Pharmacokinetics
Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is 
essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the 
assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. This leads 
to the production of microtubule bundles without normal function and to the stabilization of microtubules, 
which results in the inhibition of mitosis in cells. Docetaxel's binding to microtubules does not alter the 
number of protofilaments in the bound microtubules, a feature which differs from most spindle poisons 
currently in clinical use.
The most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, 
febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation,


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anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, 
skin reactions, and myalgia.
Every 3 week docetaxel at 75 mg/m2 in combination with prednisone 5 mg BID has been evaluated in a 
randomized phase 3 study in metastatic castration-resistant prostate cancer. In the TAX327 phase 3 study, 
every 3 week docetaxel + prednisone prolonged median survival from 16.5 months (95% CI 14.4-18.6) 
for patients treated with standard of care mitoxantrone + prednisone to 18.9 months (95% CI 17.0-21.1) in 
patients treated with every 3 week docetaxel (p = 0.009). Weekly docetaxel was also evaluated in this trial 
and displayed a numerically prolonged survival compared to mitoxantrone (17.4 versus 16.5 months) 
which did not meet statistical significance (p = 0.36). The results of this trial led to the FDA approval of 
docetaxel plus prednisone in mCRPC and established every 3 week docetaxel as the standard first-line 
chemotherapy in mCRPC.
1.6
Rationale for the Starting Dose Level and Dose Schedule of Docetaxel and Ribociclib
The starting dose of docetaxel is fixed for all dose levels at 75 mg/m2 every 3 weeks. Docetaxel dosed at 
75 mg/m2 every 3 weeks was shown to be superior to weekly docetaxel with respect to efficacy outcomes 
in a prior randomized phase 3 study. If excess toxicity (particularly hematologic) is observed at the first 
dose level of the combination of ribociclib plus docetaxel, an alternative dosing schema may be pursued 
with 60 mg/m2 docetaxel every 3 weeks and/or weekly docetaxel dosing upon review of safety results 
with Principal Investigator. Both 60 mg/m2 every 3-week docetaxel as well as weekly docetaxel have 
demonstrated efficacy and less hematologic toxicity compared with 75 mg/m2 every 3 week docetaxel 
dosing.
The starting dose of ribociclib in the Phase 1b portion of the study will be 200 mg/day days 2-14 of every 
21 day cycle. The rationale for starting ribociclib on day 2 as opposed to day 1 of the treatment cycle 
stems from prior pre-clinical observations that synergistic activity is observed with taxane plus CDK4/6 
inhibition when taxane treatment is delivered prior to CDK inhibition.14 A similar sequential dosing 
strategy was successfully implemented in a phase 1b study of paclitaxel in combination with the CDK 
inhibitor dinaciclib in patients with triple negative breast cancer.
The starting dose of ribociclib (200 mg/day) is predicted to achieve serum concentrations above the level 
necessary for CDK 4/6 inhibition based upon pre-clinical studies (IB). The maximal dose of ribociclib 
(600 mg/day) to be evaluated in the current study is the recommended single agent phase 2 dose. A 
schedule of 2 weeks on, 1 week off is based upon the observation from initial clinical studies of ribociclib 
indicating the onset of cytopenias at approximately day 15 of each treatment cycle, and full recovery after 
a 7 day treatment break. Preliminary clinical data do not indicate a compromise in disease efficacy with a 
one week treatment break with ribociclib.
1.7
Rationale for the Correlative Studies
Tissue and Peripheral Blood Assays of MYC Pathway Activation:
Putative resistance and sensitivity markers of CDK 4/6 inhibitors including Rb1 loss (resistance), cyclin 
D2 overexpression (sensitivity), CDK 4/6 overexpression (sensitivity), MYC overexpression and 
amplification (sensitivity) will be assessed in an exploratory fashion during the Phase 2 portion of the 
study to determine whether there are particular indicators of clinical benefit with CDK4/6 inhibition in 
specific patient populations.
Patients will undergo optional metastatic tumor biopsy prior to day 1 of study treatment during Phase 2 
of the study. Preliminary data indicates high rate of evaluable biopsy material from metastatic prostate 
tumor biopsies, including bone (yield 70-90%). For the UCSF patients undergoing tumor biopsy during 
Phase 2, the infrastructure from the ongoing clinical study 
 will be utilized for tissue 


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analysis, including RNA sequencing to determine levels of gene expression of MYC pathway elements.
Peripheral blood (all patients) will also be collected for circulating tumor cell (CTC) and cell-free 
circulating tumor DNA (ctDNA) analysis at Screening (phase 2 only). In past studies, collection of 
CTCs and cell-free ctDNA has been feasible and results have had reasonable concordance with 
metastatic tumor tissue. 
Gallium citrate PET Imaging (Optional - For UCSF Patients Only)
In considering non-invasive strategies to more expediently investigate the role of MYC in mCRPC, 
several groups have reported preclinical data showing that a small handful of radiotracers can measure 
MYC biology by targeting a downstream event regulated by MYC. Among these include radiolabeled 
transferrin (Tf) adducts, which provide a readout of intracellular MYC activity by detecting expression 
changes in the transferrin receptor (TFRC), a direct and specific MYC target gene (Fig. 2A). When 
considering clinically available radionuclides to non-invasively quantify MYC transcriptional
activity, 68Ga-citrate-based PET possesses a strong rationale to evaluate in this setting: (1) Gallium citrate 
rapidly and specifically binds transferrin in vivo, providing in turn a quantifiable read-out of transferrin
receptor density and therefore MYC transcriptional activity (Fig. 2B); (2) As compared with gallium-67, 
gallium-68 has a much shorter half-life (68 m vs. 3.2 d) and decays primarily by positron emission (67Ga: 
multiple single photon emission at 93, 184, and 300 keV) allowing higher doses to be injected and shorter 
imaging studies. 68Ga is readily available from the germanium-68 generator; (3) 68Ga-citrate does not 
accumulate within the pulmonary parenchyma, allowing for markedly improved sensitivity and specificity 
in detecting regions of transferrin receptor overexpression  (4) 68Ga-citrate imaging has an established
pre-clinical and clinical safety and dosimetry record, and is available for clinical use. Indeed, proof-of- 
concept PET imaging studies in humans have already shown that it can target foci harboring cells with 
high TFRC expression (e.g. peripheral mononuclear blood cells at sites of infection).20


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Figure 2: Measuring MYC signaling in prostate cancer with 68Ga-citrate PET. A. A schema summarizing the 
biological hypothesis of the grant.  At left, systemic abiraterone (Abir.) treatment will affect a disease  response
by inhibiting the production of androgens like testosterone (test.) and preventing the androgen receptor (AR) 
from performing transcription at androgen response elements (AREs). Alternatively, a subset of disease will 
escape control by virtue of AR’s ability to transcribe MYC in a ligand independent fashion. In addition AR 
independent MYC expression can override clinical benefit associated with single agent inhibitors of AR. MYC 
in turn transcribes a large repertoire of target genes responsible for proliferation and survival. Among these are 
the transferrin receptor (TFRC), an essential regulator of iron homeostasis, and cyclin dependent kinases 4 and  
6 (CDK4/6), two of a family of enzymes that regulate cell cycle progression. Diagnostically, we hypothesize  
that MYC overexpressing tumors will be identified with a Gallium-68 (Ga)/transferrin adduct on the basis of 
high TFRC expression. Therapeutically, we hypothesize that patients with disease highly avid for gallium- 
citrate will most demonstrably respond to CDK4/6 inhibition with ribociclib on the basis of an “addiction” to 
MYC signaling. B. A summary of the region of interest analysis for MYC dependent gallium-68 citrate uptake 
in mouse prostate cancer xenograft models. Mice were inoculated with MycCaP, a model in which MYC is 
regulated by ligand activated AR, or MycCaP + MYC, a MycCaP subline that also harbors an additional MYC 
allele with a constitutive promoter. Castration resulted in a rapid downregulation of gallium-68 citrate uptake in 
the MycCaP tumor, but no substantial change in uptake for the MycCaP + MYC tumor model. This finding is 
consistent with the model of MYC regulation of TFRC outlined in A.


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2
STUDY OBJECTIVES 
2.1
Primary Objectives:
Phase 1b:
To determine the safety profile, maximally tolerated dose (MTD), and recommended phase 2 dose of 
ribociclib in combination with docetaxel plus prednisone in patients with mCRPC.
Phase 2:
To determine the 6-month radiographic progression-free survival rate with the combination of ribociclib, 
docetaxel, and prednisone in patients with mCRPC.
2.2
Secondary Objectives:

To determine the median radiographic progression-free survival with the combination of 
ribociclib, docetaxel, and prednisone in patients with mCRPC.

To determine the objective response rate and median duration of response among patients with 
measurable disease at baseline.

To determine the PSA response proportion and time to PSA progression.

To characterize the safety profile of ribociclib in combination with docetaxel.

To determine if there is evidence of drug-drug interaction between docetaxel + prednisone with 
ribociclib.
2.3
Exploratory 
Objectives:

To determine whether baseline or percent change from baseline in gallium citrate uptake on PET 
scan is associated with clinical outcomes (For UCSF Patients Only).

To determine whether genomic assessment of MYC pathway activation (MYC amplification or 
overexpression, Rb1 deletion, cyclin D/E and CDK 4/6 overexpression) assessed within 
metastatic tumor tissue, CTCs, and/or cell-free ctDNA is predictive of clinical outcomes with 
the combination of ribociclib plus docetaxel.

To determine whether MYC activation score as determined by validated expression signature can 
distinguish those with and without clinical benefit with ribociclib in combination with docetaxel.

To use an unbiased approach with integration of clinical, genomic, and proteomic data 
(Differential Pathway Signature Correlation; DiPSC) to define a signature associated with 
response to taxane + CDK4/6 inhibition in mCRPC.


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3
STUDY DESIGN
3.1
General Study Design
This is a Phase Ib/II open label clinical trial in patients with metastatic castration resistant prostate cancer. 
The objective of the phase Ib portion of the study is to establish the maximum tolerated dose (MTD) and 
dose limiting toxicities (DLT) of docetaxel and prednisone in combination with ribociclib in escalating 
oral daily doses in patients with metastatic CRPC with prior resistance to abiraterone and/or enzalutamide 
who have not undergone prior chemotherapy for metastatic disease. Dose escalation will follow the 
standard 3+3 design. The initial dosing schedule was chosen to allow patients to be exposed to the most 
efficacious dosing schedule of docetaxel (75 mg/m2 every 3 weeks). If there is excess toxicity observed 
with the treatment combination at the first dose level (dose level I), an alternative dosing schema may be 
pursued with docetaxel 60 mg/m2 every 3 weeks and/or weekly docetaxel treatment (30 mg/m2 weekly 
two of every three weeks). Both of these alternative docetaxel dosing schedules have demonstrated 
activity in mCRPC with decreased risk of cytopenias compared with 75 mg/m2 every 3 week. 
Intermediate dose levels and/or alternative dosing schedules of ribociclib may be investigated in Phase Ib 
based on the initial safety data. 
The Phase 2 portion (N = 29) of the study is a single arm, two stage, open-label study of ribociclib (dosed 
at the RP2D and schedule) in combination with docetaxel and prednisone to determine the efficacy and 
further define the safety of the treatment combination. Patients will be treated with the combination of 
ribociclib plus docetaxel + prednisone for up to 9 cycles. If there is no evidence of radiographic or clinical 
disease progression after 9 cycles of protocol therapy, patients may continue on single agent maintenance 
ribociclib until the time of disease progression. Patients will have the option of starting maintenance 
ribociclib after 6 cycles of docetaxel if stable disease or better on re-staging scans. The dose of ribociclib 
used during maintenance will be the same dose as that immediately preceding cessation of docetaxel 
treatment.


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3.2
Inclusion Criteria
Patients eligible for inclusion in this study must meet all of the following criteria:
1.
Histologically confirmed prostate cancer. Small cell/neuroendocrine differentiated allowed but 
not required for study participation.
2.
Progressive metastatic prostate cancer (as defined below in Item #5) despite castrate levels of 
testosterone (< 50 ng/dL).
3.
Patients may have either non-measurable disease OR measurable disease
4.
Progressive disease during (or within 4 weeks of completion) with abiraterone, enzalutamide, 
and/or ARN-509 based on any one of the following:
a.
For patients with measurable disease, progression by the RECIST criteria.13
b.
PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml 
which has risen on at least 2 successive occasions, at least one week apart. If the 
confirmatory PSA (#3) value is less (i.e., #3b) than the baseline PSA (#2) value, then an 
additional test for rising PSA (#4) will be required to document progression for the purposes 
of eligibility.
c.
Radionuclide bone scan: At least two new foci consistent with metastatic lesions
5.
Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH 
analogue if they have not undergone orchiectomy.
6.
Patients treated with first generation anti-androgen as most recent systemic therapy (bicalutamide, 
nilutamide) must have at least 4 weeks elapsed from treatment discontinuation to start of protocol 
therapy with evidence of disease progression by PCWG2 criteria following discontinuation of 
prior anti-androgen.
igibility Based on PSA
#3a
#4
#2
#3b
#1
Reference 
value
El
Figure 1
>/=1wk


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7.
ECOG Performance Status 0 or 1 (see Appendix 1).
8.
Patient has adequate bone marrow and organ function as defined by the following laboratory 
values:
•
Absolute neutrophil count ≥ 1.5 × 109/L.
•
Platelets ≥ 100 × 109/L.
•
Hemoglobin ≥ 9 g/dl.
•
Potassium, total calcium (corrected for serum albumin), magnesium and sodium within 
normal limits for the institution or corrected to within normal limits before first dose of study 
medication.
•
INR ≤ 1.5 unless on direct thrombin inhibitor at time of study entry.
•
Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min
•
In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate 
aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and AST <5 x 
ULN
•
Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in 
patients with well-documented Gilbert’s Syndrome.
9.
No other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is 
shorter, prior to day 1 of study therapy.
10. Sexually active males must use a condom during intercourse while taking the drug and for 30 
days after stopping treatment and should not father a child in this period. A condom is required to 
be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. 
Fertile males must use a condom with spermicide (double barrier method).
11. Age ≥ 18 years
12. Written informed consent must be obtained prior to any screening procedures and according to 
local guidelines.
3.3
Exclusion Criteria
Patients eligible for this study must not meet any of the following criteria:
1.
Patient has a known hypersensitivity to ribociclib or any of its excipients including peanuts and 
soy, or prior treatment with CDK 4/6 inhibitor.
2.
Prior chemotherapy for metastatic castration-resistant prostate cancer. Chemotherapy 
administered in the castration-sensitive setting is allowed provided last dose of chemotherapy was 
greater than 12 months prior to study entry
3.
Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the 
exception of adequately treated non-melanomatous skin cancer and superficial bladder cancer 
(including carcinoma-in-situ).
4.
Patients with central nervous system (CNS) involvement unless they meet ALL of the following 
criteria:

At least 4 weeks from prior therapy completion (including radiation and/or surgery) to 
starting the study treatment


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
Clinically stable CNS tumor at the time of screening and not receiving steroids and/or 
enzyme-inducing anti-epileptic medications for brain metastases.

Baseline screening for CNS metastases is not required unless presence of signs and/or 
symptoms of involvement
5.
Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) 
function or GI disease that may significantly alter the absorption of the study drugs (e.g., 
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or 
significant small bowel resection).
6.
Clinically significant, uncontrolled heart disease and/or recent events including any of the 
following:
•
History of acute coronary syndromes (including myocardial infarction, unstable angina, 
coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis 
within 12 months prior to Screening
•
History of documented congestive heart failure (New York Heart Association functional 
classification III-IV)
•
Patient has a left ventricular ejection fraction (LVEF) < 50% as determined by Multiple 
Gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during Screening.
•
History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or 
conduction abnormality within 12 months of Screening. Patients with rate-controlled atrial 
fibrillation or flutter are permitted.
•
Bradycardia (heart rate < 50 bpm at rest), by ECG or pulse, at Screening
•
Congenital long QT syndrome or family history of long QT syndrome
•
Any of the following abnormalities on Screening 12-lead ECG:
o
QTcF > 450 msec
o
Bradycardia (heart rate < 50 bpm at rest)
o
Tachycardia (heart rate > 100 bpm at rest) 
o
PR interval > 220msec,
o
QRS interval >109 msec
•
Documented cardiomyopathy
•
Systolic blood pressure >160 mmHg or <90 mmHg at Screening
7.
AST and/or ALT > 1.5 x ULN with concomitant alkaline phosphatase > 2.5 x ULN
8.
Patient receiving any of the following medications (see Appendix 2) within 7 days of day 1 of 
study treatment.
•
Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, 
pummelos, star-fruit, and Seville oranges
•
That have a narrow therapeutic window and are predominantly metabolized through 
CYP3A4/5.
•
That have a known risk to prolong the QT interval or induce Torsades de Pointes.
•
Herbal preparations/medications that are strong inhibitors or inducers of CYP3A4/5 or those 
with a known risk of QT prolongation.
9.
Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting 
study drug at a dose greater than the equivalent of 10 mg prednisone/day, or who have not fully 
recovered from the side effects of such treatment
a.
The following uses of corticosteroids are permitted: single doses, topical applications 
(e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local 
injections (e.g., intra-articular).


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10. Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, 
prophylaxis or otherwise. Therapy with heparin, direct thrombin inhibitors, low molecular weight 
heparin (LMWH) or fondaparinux is allowed.
11. Major surgery within 14 days prior to starting study drug or has not recovered from major side 
effects (tumor biopsy is not considered as major surgery).
12. Patient who has received radiotherapy ≤ 4 weeks prior to starting study drug, and who has not 
recovered to grade 1 or better from related side effects of such therapy (exceptions include 
alopecia), and/or in whom ≥25% of the bone marrow was irradiated.
13. Prior treatment with radiopharmaceutical including radium-223, strontium-89, or samarium-153.
14. Patient has a known history of HIV infection (testing not required)
15. Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE 
version 4.03 to less than or equal to Grade 1 (Exception to this criterion: patients with any grade 
of alopecia are allowed to enter the study).
16. Patients with chronic liver disease with a Child-Pugh score B or C.
17. Patients with serious intercurrent infections, or nonmalignant medical illnesses that are 
uncontrolled or whose control may be jeopardized by the complications of this therapy.
18. Patients with severe psychiatric illness/social situations that would limit compliance with study 
requirements in the judgment of study investigator.
19. History of bleeding diathesis. 
20. Patient has a history of non-compliance to medical regimen or inability to grant consent
21. Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-
lives of the investigational product, whichever is longer
4
SUBJECT REGISTRATION AND ENROLLMENT
4.1
Subject Recruitment & Study Sites
Patients will be screened for interest and eligibility by the medical oncologists in the Urologic Oncology 
Practice at the UCSF Cancer Center and by other participating study sites per their local recruitment and 
screening practices. Patients to be screened will include those currently followed in the UCSF practices 
including those referred from outside providers, as well as other participating Study Sites per their local 
practice.
4.2
Registration Procedures
Prior to registration, patients will be asked to sign and date an Institutional Review Board (IRB)-approved 
consent form and a research authorization form/Heath Insurance Portability and Accountability Act


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(HIPAA) authorization form. All eligible patients must be centrally registered through the Prostate Cancer 
Clinical Trials Consortium, LLC (PCCTC).  To complete the registration process, the study site must 
email the signed completed study-specific eligibility checklist, all source documents verifying eligibility, 
any supporting documents, and the signed informed consent to PCCTC 
. UCSF is the 
only site exempt from submitting source documents and supporting documents and is only required to 
submit the signed, completed study-specific eligibility checklist and informed consent to PCCTC. Once 
the enrollment packet is received and reviewed at PCCTC and if eligibility is confirmed, assignment to 
treatment can occur and the patient will be enrolled in Medidata Rave®, the Electronic Data Capture 
(EDC) system for this study.  Study Chair will be knowledgeable of all registrations. Participating sites 
will register patients locally per their Institutional guidelines in addition to central registration with 
PCCTC. Patients failing to meet all study eligibility requirements will not be registered.
5
SCHEDULE OF ASSESSMENTS
5.1
Pre-treatment Evaluation
5.1.1
Clinical (within 14 days prior to registration)
a.
Complete history and physical examination, including height, weight, and baseline 
evaluation of symptoms, pain and medications
b.
Performance Status (ECOG/KPS scale) – Appendix 8
c.
EKG
5.1.2
Laboratory (within 14 days prior to registration)
a.
Complete blood count including differential and platelet count
b.
Chemistry panel: Alkaline phosphatase, albumin, total bilirubin, BUN, calcium, 
creatinine, glucose, LDH, AST, ALT, sodium, potassium, bicarbonate, chloride,
magnesium
c.
PT/INR + PTT
d.
PSA
e.
Testosterone level (may be obtained within 28 days prior to registration)
f.
CTCs and cell-free ctDNA (Phase 2 only)
5.1.3
Radiographic and Diagnostic Studies (within 42 days of registration)
a.
Radionuclide bone scan
b.
CT scan of the chest, abdomen and pelvis (with IV contrast if kidney function is 
adequate. MR abdomen/pelvis is acceptable).
d.
MUGA or echocardiogram (may be performed within 42 days of initiating treatment 
in both Phase 1 and Phase 2)
e.
Gallium-citrate PET scan (Optional, UCSF Patients Only - Phase 2 only). PET scan 
should be performed prior to tumor biopsy (see below)
5.1.4
Tumor biopsy (within 28 days of registration; optional):
Core or excisional biopsy preferred over fine needle aspiration.


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5.2
Evaluations during treatment and end-of-treatment 
Phase 1b Schedule (N ~ 9-18 evaluable patients):
a. Screening labs may be used on Cycle 1Day 1 if drawn within 3 days prior to start of treatment.
b. For every 3-week docetaxel dosing schedule, CBC + differential will be measured Days 1, 8, and 15 
of Cycle 1, Days 1, 8 (+/- 2 days), and 15 (+/- 2 days) during Cycles 2-3, and then on Day 1 of Cycle 4 
and every cycle thereafter. For weekly docetaxel dosing schedule, CBC + differential will be measured 
on Days 1, 8, and 15 of Cycle 1, Days 1, 8, and 15 (+/- 2 days) during Cycles 2-3, and then on Days 1 
and 8 of every cycle thereafter. Chemistry panel as described in Section 5.1.2.
c. 12-lead ECG will be performed during Screening, pre-dose Cycle 1 Day 15, pre-dose Cycle 2 Day 1, 
and on Day 1 of every cycle thereafter (pre-dose).
d. PK assessment schedule: 
Ribociclib:
C1D1: Pre-dose, t + 1 hour post dose (+/- 5 min), t + 2 hours post dose (+/- 5 min), t + 4 hours post-dose 
(+/- 5 min)
C1D2: t + 24 hours post-dose (+/- 1 hour) 
Docetaxel:
C1D2: t + 24 hours post-dose (+/- 1 hour)
Please see Appendix 4 for additional details
e. Tumor assessment will be completed at the completion of every 3 treatment cycles (9 weeks). Tumor 
assessment to include CT chest/abdomen/pelvis (with IV contrast if no allergy and adequate renal 
function) and radionuclide bone scan. MRI abdomen/pelvis is an acceptable alternative.
f. For every 3 week dosing schedules, docetaxel will be administered on Day 1 of every 21-day cycle, 
with concomitant prednisone 5 mg BID. For weekly dosing schedule, docetaxel will be administered on 
Days 1 and 8 of every 21-day cycle. Treatment will be administered for up to 9 cycles. If there is no 
evidence of clinical or radiographic progression, patients will discontinue docetaxel and taper prednisone 
over a period of 21 days. Patients with stable disease or better as best response will have the option of
Study Assessments
Screena
Cycle 1
Cycle 2 and Every Cycle 
Thereafter
End of Study 
(within 30 days 
of last 
treatment)
D 1
D2
D8
D15
Day 1
Informed Consent
X
Medical History
X
Physical Examination
X
X
X
X
X
X
X
Concurrent Medications
X
X
X
X
X
X
ECOG Performance 
Status
X
X
X
X
X
X
X
Adverse Event 
Assessment
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
Weight and Height
X
X
X
X
CBC + Differentialb
X
X
X
X
X
X
PT/PTT + chemistry 
panelb
X
X
X
X
X
X
Serum PSA
X
X
X
X
Serum testosterone
X
MUGA or echocardiogram
X
12-lead ECGc
X
X
X
Pharmacokineticsd
X
X
Tumor Assessmente
X
X
X
Docetaxel Administrationf
X
X
Neupogen Administrationg
See Section 6 for schedule
Ribociclib Administration
Dosed Daily (see Section 6 for schedule)  


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discontinuing docetaxel after 6 cycles of protocol therapy. The dose schedule of maintenance ribociclib 
monotherapy will be the dose used immediately preceding discontinuation of docetaxel, given on days 1- 
14 of every 21-day cycle.
g. Neupogen will be administered subcutaneously daily on days 15-18 of every cycle. Dose will be 
determined by actual body weight (300 mcg if < 70 kg on C1D1; 480 mcg if ≥ 70 kg). Alternative 
dosing schedules of neupogen may be utilized depending on dosing schedule of study therapy 
(see Section 6). 


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Phase 2 Schedule (N = 29 evaluable patients)
Cycle 1
Cycle 2 and Every Cycle 
Thereafter
End of Study (within 
30 days of last 
treatment)
Study Assessments
Screena
D 1
D8
D15
Day 1
Informed Consent
X
Medical History
X
Physical Examination
X
X
X
X
X
X
Concurrent Medications
X
X
X
X
X
X
ECOG/KPS Performance 
Status
X
X
X
X
X
X
Adverse Event 
Assessment
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
Weight and Height
X
X
X
X
CBC + Differentialb
X
X
X
X
X
X
PT/PTT + chemistry 
panelb
X
X
X
X
Serum PSA
X
X
X
X
Serum testosterone
X
MUGA or echocardiogram
X
12-lead ECGc
X
X
X
CTC and Cell-Free 
ctDNA collectiond
X
Plasma/serum/PBMC 
bankinge
X
X
X
Tumor Biopsyf
X
Gallium citrate PETg
X
X
Tumor Assessmenth
X
X
X
Docetaxel Administrationi
X
X
   Neupogen Administrationj
See Section 6 for schedule
Ribociclib Administrationk
Dosed Daily (see Section 6 for schedule)
a. Screening labs may be used on Cycle 1 Day 1 if drawn within 3 days prior to start of treatment.
b. For every 3-week docetaxel dosing schedule, CBC + differential will be measured Days 1, 8, and 15 
of Cycle 1, Days 1, 8 (+/- 2 days), and 15 (+/- 2 days) during Cycles 2-3, and then on Day 1 of Cycle 4 
and every cycle thereafter. For weekly docetaxel dosing schedule, CBC + differential will be measured 
on Days 1, 8, and 15 of Cycle 1, Days 1, 8, and 15 (+/- 2 days) during Cycles 2-3, and then Days 1 and 
8 of every cycle thereafter. Chemistry panel as described in Section 5.1.2
c. 12-lead ECG will be performed during Screening, Cycle 1 Day 15, and on Day 1 of every 
cycle thereafter.
d. See Section 5.4 and 5.5 and Appendix 6 regarding collection instructions
e. Plasma/serum/PBMC banking is optional. Peripheral blood mononuclear cells (PBMCs) will be 
collected and banked at baseline. Serum/plasma will be banked at baseline, every 3 months (+/- 4 
weeks) from Cycle 1 Day 1 until treatment discontinuation, and at the time of disease progression.
f. Optional tumor biopsy to be performed in patients with accessible lesion. Biopsy to be performed at 
Screening following completion of Screening scans including gallium citrate PET. Results of pathologic 
analysis do not need to be available prior to initiation of protocol therapy provided there is prior pathologic 
confirmation of prostate cancer. See Section 5.6 and Appendix 7 for collection/processing information.
g. Optional Gallium-68 citrate PET scan to be completed at Screening and on Cycle 2 Day 1 of protocol 
therapy (+/- 7 days) (UCSF patients only). See Section 5.7 for details regarding the scan/ procedure.


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h. Tumor assessment will be completed at the completion of every 3 treatment cycles (9 weeks). Tumor 
assessment to include CT chest/abdomen/pelvis (with IV contrast if no allergy and adequate renal 
function) and radionuclide bone scan. MRI abdomen/pelvis is an acceptable alternative.
i. For every 3 week dosing schedules, docetaxel will be administered on Day 1 of every 21-day cycle, 
with concomitant prednisone 5 mg BID. For weekly dosing schedule, docetaxel will be administered on 
Days 1 and 8 of every 21-day cycle. Treatment will be administered for up to 9 cycles. If there is no 
evidence of clinical or radiographic progression, patients will discontinue docetaxel and taper prednisone 
over a period of 21 days. Patients with stable disease or better as best response will have the option of 
discontinuing docetaxel after 6 cycles of protocol therapy. The dose schedule of maintenance ribociclib 
monotherapy will be the dose used immediately preceding discontinuation of docetaxel, given on Days 1- 
14 of every 21-day cycle.
j. Neupogen will be administered subcutaneously daily on days 15-18 of every cycle. Dose will be 
determined by actual body weight (300 mcg if < 70 kg on C1D1; 480 mcg if ≥ 70 kg). Alternative 
dosing schedules of neupogen may be utilized depending on the recommended phase 2 dosing 
schedule of study therapy (see Section 6.2).
k. Ribociclib daily dose and schedule to be determined from Phase 1 portion of study.
5.3
Plasma/Serum/Peripheral Blood Mononuclear Cell (PBMC) Banking
Blood will be collected at specified time points for Plasma, Serum, and PBMC banking. The UCSF-
HDFCCC Tissue Bank will serve as a repository for banking human samples. Specimen and data 
registries will be kept by the UCSF-HDFCCC. This registry will have a coordinated database to protect 
patient confidentiality and safety. The samples will receive a patient- insensitive identifier and the link to 
patient identity will be kept in a locked file with access only by the director of the Tissue Bank. Other 
investigators will have access to the samples only through established Tissue Core procedures. That is, 
investigators must submit a written request to use the stored samples as part of an IRB-approved protocol 
that is reviewed by the Tissue Core committee. This review limits the testing that can be done on these 
samples. No information about germ-line genetic mutations will be done on these samples. The collection 
of these specimens is optional and patients have the right at any time to request that all remaining 
samples be destroyed. The patient or relatives may be contacted about future, additional research on 
stored samples, if necessary. Additional written consent will be required if additional samples are to be 
taken. Please see Appendix 5 for additional details.
5.4
Cell-Free Circulating Tumor DNA
A next generation DNA sequencing platform will be utilized in the current study. The platform is fully 
CLIA-certified and assesses many of the most common driver mutations encountered across solid tumor 
malignancies, including complete exon and partial intron coverage of, RB1, MYC, AR, and PTEN, 
CDK4, CDK6, CCND1, CCND2, among others. In addition, copy number determination of MYC, 
CDK4, and CDK6 will be determined. For the specimen collection, 10 mL of whole blood will be 
collected using the supplied research kit with blood collection tubes at Screening. Samples will be 
shipped to Guardant Health. Please see Appendix 6 for collection and shipping instructions.
5.5
Circulating Tumor Cells
CTC enumeration will be performed via the Epic Sciences platform. The Epic Sciences platform is a 
novel CTC detection technology that uses unselected enumeration and characterization of multiple 
different CTC types including “traditional” CTCs (CK+, CD45-, and morphologically distinct from 
surrounding white blood cells, similar to the Veridex definition), EMT candidates (CK-, CD45-, and 
morphologically distinct from surrounding white blood cells), and small cell CTCs (CK+, CD45-, and 
morphologically similar to white blood cells). The technology was developed with a view to providing a 
fluid biopsy with features, specifications and performance criteria similar to current pathology practice. 
The platform allows multiplexed analysis of different protein biomarkers from the


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same blood sample, fluorescence in-situ hybridization (FISH) analysis of relevant genes, and individual 
cell capture for detailed molecular interrogation. The platform has demonstrated molecular 
characterization concordance in a blinded CRPC patient study between concurrently obtained biopsies of 
bone metastases and Epic-captured CTCs. In the study, 80% (12 of 15) of tumors with PTEN loss in the 
bone biopsy also harbored PTEN loss in Epic CTCs, demonstrating a strong genomic concordance and 
the ability to measure intra-patient genomic heterogeneity. Please see Appendix 6 for collection and 
processing details.
5.6
Tumor biopsy (Optional, if accessible lesion is present)
Optional image-guided biopsies will be performed prior to start of protocol therapy. Lesions will be 
chosen based upon the strength of the evidence suggesting the presence of metastasis and with the goal 
of minimizing patient risk. Soft tissue lesions and lesions with documented radiologic progression 
should be prioritized for biopsy. If the Radiologist in charge of the procedure cannot identify a lesion 
amenable for biopsy, the patient will still be eligible for study participation. 
Biopsies will be performed in an interventional radiology suite with radiological guidance (typically CT 
or MRI) in accordance with the standard operating procedure in Appendix 7 and institutional standards. 
CT or MRI will confirm designated lesions immediately prior to biopsy. Once the target lesion(s) is 
identified, up to six (6) cores will be obtained. Preferably, a 16-gauge BonoptyTM needle or biopsy needle 
with an equivalent 16-gauge bore will be used to biopsy the metastatic lesion. If the lesion is a bone 
metastasis, the Bonopty needle will be passed through the cortical bone and into the target lesion. 
Optimal results are obtained when the biopsies are performed on medullary bone directly adjacent to a 
blastic lesion. Soft tissue biopsies should be performed to ensure a core of approximately 10 to 20 mm in 
length is obtained. Extracted cores will be immediately frozen on a pre-frozen bed of OCT (Optimal 
Cutting Temperature compound used for frozen sections), covered with additional OCT, and stored at -
80° C until shipment (see Appendix 7). All biopsy specimens will be delivered to the Feng laboratory at 
UCSF.
Frozen biopsies will be processed for RNA analysis using laser capture microdissection (LCM) and RNA 
amplification using adaptations of previously published methods 36. Briefly, 8-micron frozen sections are 
obtained from each biopsy specimen and stained with H&E. Sections will be loaded into the Aperio 
Digital Imaging system. Multiple sequential 8-micron biopsies are performed prior to rapid H&E staining 
and dehydration with sequential immersion in xylene. The air-dried slides are put into a LCM system and 
prostate cancer cells are identified and collected. Cell material selected for analysis is dissolved in RNA 
or DNA isolation buffer and RNA and DNA are isolated separately using standard commercially 
available kits. RNA and DNA are quantified using the RiboGreen or PicoGreen kits (Invitrogen, Inc) and 
RNA quality is assessed with an Agilent 2100 Bioanalyzer using the RNA 6000 Pico Kit (Agilent, Inc). 
Similarly, DNA is collected from separate but adjacent frozen sections and isolated. DNA is quantified 
using PicoGreen quantification.
Gene copy number changes will be performed using a CGH methodology as described above in Section
5.5. RNA sequencing methodology will be used to determine levels of gene expression. LCM collected 
material will be lysed with 5 microliters of Prelude Lysis Buffer (NuGen, San Carlos, CA); subjected to 
cDNA synthesis and amplification without transfer (NuGen, Ovation RNA-seq with some modifications 
to standard protocol); selected for size and processed using the mixed cDNA standard library preparation 
performed using TruSeq protocol (Illumina, San Diego, CA). Paired-end sequencing will be performed on 
the Illumina HiSeq 2000.


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5.7
Gallium-68 Citrate PET Scan (Optional, For UCSF Patients Only)
Ga-68 citrate is a radiopharmaceutical that will be produced under cGMP under the direction of 
 
the Department of Radiology and Biomedical Imaging Radiopharmaceutical Facility, 
The radiopharmaceutical will be prepared in the same facility in which the injection and imaging will 
take place, the China Basin Imaging Center. Ga-68 citrate will be administered on an outpatient basis. 
It will be administered a single time intravenously prior to PET imaging. The one-time nominal 
injected dose will be up to 20  mCi Ga-68.
Patient shall begin imaging within 6 hours following injection of the radiopharmaceutical. Coverage 
for the scan will extend from the patient’s vertex through the toes. The entire imaging study will take 
roughly 60 minutes.
No formal report of the findings from imaging studies will be created.  Each study will be reviewed by 
a board certified nuclear medicine physician and radiologist within two working days of the completion 
of the study. If any unexpected findings are visualized, these will be reported to the treating health care 
provider, who will then contact the patient if additional work-up needs to be performed.


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6
TREATMENT PLAN
6.1
Dose and schedule
1.
Each cycle is 21 days long. A ± 3 day window is allowable for administration of chemotherapy for 
scheduling purposes for cycle 2 and beyond.
2.
Two separate dose guidelines will be used in this trial:
a.
Cohort dose level (referred to by Roman numerals: I, II, III, etc).
b.
Individual patient dose level: individual patients may have their doses modified (reduced) for 
toxicity (referred to by Arabic numerals: 0, -1, -2).
There are approximately 3 planned dose cohorts in the Phase 1 portion of the study. Approximately 
9 to 18 patients will be treated on the Phase 1 portion of the study.
3. The starting cohort dose level for docetaxel will be 75 mg/m2, administered on day 1 of each cycle. 
Prednisone will be fixed at 5 mg PO BID. The starting dose level and schedule for ribociclib will be 
200 mg orally once daily, starting on day 1 of the 21-day cycle.
4. If dose level I is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting 
with dose level IA. 
5. Depending on the safety data observed, alternative dosing schedules and intermediate dose levels of 
ribociclib may be investigated as outlined in Table below (Cohort Dose Levels IC – IIIC). 
Cohort Dose Levels (3+3 Design)
Patient number
Docetaxel 
(day 1 of 21- 
day cycle)
Ribociclib Daily
Prednisone
Filgrastim*
I**
3+3
75 mg/m2
200 mg/day
5 mg PO BID
SubQ daily days 
15-18
II
3+3
75 mg/m2
400 mg/day
5 mg PO BID
SubQ daily days 
15-18
Dose Level
III
3+3
75 mg/m2
600 mg/day
5 mg PO BID
SubQ daily days 
15-18


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Alternate Dosing Schema with Docetaxel 60 mg/m2  (3+3 Design)
Patient number
Docetaxel 
(day 1 of 21- 
day cycle)
Ribociclib 
Daily
Prednisone
Filgrastim*
IA
3+3
60 mg/m2
200 mg/day
5 mg PO BID
SubQ daily days 
15-18
IIA
3+3
60 mg/m2
400 mg/day
5 mg PO BID
SubQ daily days 
15-18
Dose Level
IIIA
3+3
60 mg/m2
600 mg/day
5 mg PO BID
SubQ daily days 
15-18
Alternate Dosing Schema with Weekly Docetaxel (3+3 Design)
Patient number
Docetaxel  
(days 1, 8 of 21- 
day cycle)
Ribociclib 
Daily
Prednisone
Filgrastim*
IB
3+3
30 mg/m2
200 mg/day
5 mg PO BID
SubQ daily days 
15-18
IIB
3+3
30 mg/m2
400 mg/day
5 mg PO BID
SubQ daily days 
15-18
Dose Level
IIIB
3+3
30 mg/m2
600 mg/day
5 mg PO BID
SubQ daily days 
15-18
* Filgrastim will be administered subcutaneously daily on days 15-18 of every cycle. Dose will be determined 
by actual body weight (300 mcg if < 70 kg on C1D1; 480 mcg if ≥ 70 kg). Filgrastim may also be administered 
as clinically necessary per investigator discretion for grade 3 or higher neutropenia. It should not be 
administered within 24 hours prior to or after docetaxel infusion.
**If dose level I is determined to have exceeded the MTD alternative dosing schedules of docetaxel will be 
evaluated, as indicated above, starting with dose level IA. Dose escalation will then proceed from level IA to 
level IIIA as tolerated. If dose level IA, IIA, or IIIA is not tolerated, weekly docetaxel dosing may be explored 
starting with the corresponding dose level (e.g. IA  IB, IIA  IIB, IIIA  IIIB).
Alternative Ribociclib Dosing Schedule (3+3 Design)
Patient number
Docetaxel  (day 
1 of 21- day 
cycle)
 Ribociclib  
Daily^
Prednisone
Filgrastim*
IC
3+3
60 mg/m2
200 mg/day
5 mg PO BID
SubQ daily days 
5-7
Dose Level
IIC
3+3
60 mg/m2
300 mg/day
5 mg PO BID
SubQ daily days 
5-7


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IIIC
3+3
60 mg/m2
400 mg/day
5 mg PO BID
SubQ daily days 
5-7
* Filgrastim will be administered subcutaneously daily on days 5-7 of every cycle. Dose will be determined by 
actual body weight (300 mcg if < 70 kg on C1D1; 480 mcg if ≥ 70 kg). Additional doses of filgrastim will also 
be administered as clinically necessary for grade 3 or higher neutropenia. It should not be administered within 
24 hours prior to or after docetaxel infusion.
^ Ribociclib will be dosed daily on days 1-4, 8-15 of every 21-day treatment cycle. 
6.
The prednisone dose will be 5 mg by mouth twice a day, continuously. At the conclusion of docetaxel 
treatment, prednisone will be tapered over two weeks or longer at the discretion of the treating 
provider.
7.
When calculating body surface areas, actual heights and weights should be used. There should be no 
adjustment to “ideal” weight. The total dose delivered should be rounded to the nearest mg. The dose 
should be adjusted during each cycle for the patient’s current weight. If there has been an increase in 
weight of 5% or greater that the investigator suspects is secondary to edema, the investigator may use 
discretion to utilize the weight from the prior cycle to calculate chemotherapy dosage.
8.
Patients who do not receive at least 50% of ribociclib doses during cycle 1 for reasons other than 
toxicity will be considered inevaluable and will be replaced.


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6.1.1
Dose escalation and de-escalation rules
Ribociclib will be escalated according to the rules outlined below:
1. The dose-limiting toxicity window will be the first 21-day treatment cycle.
2. If 0 of 3 patients in a cohort experience dose limiting toxicities, then the next cohort of 3 
patients will be treated at the next higher dose level.
3. If 1 of 3 patients in a cohort experiences a DLT then the cohort will be expanded to treat an 
additional three patients. If only one of 6 patients experiences a DLT, then the next cohort of 
patients will be treated at the next higher dose level.
4. If two or more patients in a cohort experience a DLT, then the MTD has been exceeded. The 
previous dose level will be considered the MTD. 
5. If more than 1 of 6 patients experience a DLT at dose level IA then the study will be 
terminated, as the MTD cannot be determined and de-escalation from dose level IA is not 
planned.
6. Per Investigator discretion the recommended phase 2 dose/schedule of ribociclib and 
docetaxel may be established (see Section 6.2 below) in the absence of reaching MTD, based 
on the cumulative safety data of the treatment regimen. 
6.1.2
Supportive care guidelines
1.
Patients may receive full supportive care including, transfusions of blood products, growth 
factors, bone-modifying agents, antibiotics, and anti-emetics.
2.
A list of prohibited medications and medications to be used with caution is found in
Appendices 2 and 3 respectively.
3.
Radiation therapy may not be administered concurrently with protocol therapy. If the patient 
requires the need for radiation therapy during the course of protocol therapy this will be 
considered evidence of clinical progression and the patient will be removed from study.
4.
Filgrastim should not be administered within 24 hours of docetaxel infusion. Ribociclib 
should be held for grade 3 or higher neutropenia (see Section 6.3).
5.
All patients will be premedicated to prevent a hypersensitivity reaction related to docetaxel 
with intravenous or oral dexamethasone or equivalent dose of alternative steroid.
6.2
Phase 2 Dosing Schedule
The recommended phase 2 dose and schedule of ribociclib in combination with docetaxel will 
be either equivalent to or lower than the MTD (or maximally administered cumulative dose if 
MTD not reached) of the Phase 1 portion of the study. Dose modifications for individual 
patients in the event of toxicity will be similar for Phase 1b and Phase 2, and will follow 
guidelines outlined below in Section 6.3.2.


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6.3
Toxicity Management and Dose Modifications
6.3.1
Dose limiting toxicity definitions
A dose-limiting toxicity (DLT) will be defined as a treatment-regimen related toxicity as follows:
TOXICITY
DLT CRITERIA
CTCAE grade 4 neutropenia lasting more than 7 consecutive 
days
CTCAE grade 3 thrombocytopenia with significant 
hemorrhage
CTCAE grade 4 thrombocytopenia
Hematology
CTCAE grade 3 or 4 febrile neutropenia
ECG QT interval
QTc interval ≥ 501 ms on at least 2 separate ECGs
Cardiac
Cardiac toxicity ≥ CTCAE grade 3
Clinical signs of cardiac disease, such as unstable angina or 
myocardial infarction,
Gastro-intestinal
≥ CTCAE grade 3 vomiting ≥ 48 hours despite optimal anti- 
emetic therapy
≥ CTCAE grade 3 diarrhea ≥ 48 hours despite optimal anti- 
diarrhea treatment
Hepato-biliary
≥ CTCAE grade 3 total bilirubin
≥ CTCAE grade 2 ALT with a ≥ grade 2 bilirubin elevation of 
any duration in the absence of liver metastases
≥ CTCAE grade 3 ALT for >4 consecutive days 
CTCAE grade 4 ALT or AST
Grade 4 serum alkaline phosphatase >7 consecutive days
Any category
Any toxicity that results in delivery of less than 66 % of the 
expected cumulative dose of ribociclib during Cycle 1
Non-hematologic 
events
≥ CTCAE grade 3 non-hematological toxicity that delays 
administration of either study drug for more than 2 weeks
≥ CTCAE grade 3-4 non-hematologic laboratory abnormalities
Grade 3 alopecia
< 5 days of CTCAE grade 3 fatigue
Grade 3 fever or infection without neutropenia < 5 days duration
Adverse events solely related to prednisone or androgen 
deprivation therapy in the judgment of Study Investigator.
Grade 3 hypersensitivity infusion reaction to docetaxel
Grade 3-4 increase in indirect bilirubin indicative of M. 
Meulengracht/Gilbert’s syndrome
Grade 3 increase in serum lipase and/or amylase for < 7 
consecutive days without clinical signs or symptoms of 
pancreatitis
Exceptions to 
DLT criteria
Grade 3 laboratory abnormalities that are responsive to oral 
supplementation or deemed by investigator to be clinically 
insignificant
CTCAE version 4.03 should be used for grading.
Optimal therapy for vomiting and diarrhea should be based on institutional guidelines with 
consideration of the prohibited medications listed in these protocol guidelines.


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6.3.2
Guidelines for individual patient dose modifications for toxicity (Phase 1b and 
Phase 2)
6.3.2.1 General Dose Modification Guidelines
1.
Individual patient dose reduction for toxicity during the DLT window (cycle 1) in the 
Phase 1b portion of the study only will not be permitted except for toxicity meeting 
criteria for dose-limiting toxicity (Section 6.3.1).
2.
Permanently discontinue protocol therapy for related Grade 4 non-hematologic adverse 
events of any duration except for:
a.
Clinically insignificant laboratory abnormalities that resolve with optimal 
treatment within 48 hours
b.
Vomiting and diarrhea that resolve within 48 hours with optimal treatment
3.
Hold treatments for related Grade 3 adverse events with subsequent dose- 
reduction, if such adverse events return to Grade ≤ 1 or baseline within two weeks, 
treatment can be continued at one lower dose level as outlined in Section 6.3.2.7
4.
Dose reduction/discontinuation of ribociclib should occur before or concurrently with 
docetaxel for overlapping toxicities
The following sections are recommended dose interruption/reduction guidelines. Investigator- 
discretion and clinical judgment are to be utilized in deciding whether to interrupt and/or 
reduce dose even if not required per protocol.
The schema for dose modification for toxicity for individual patients are as follows:
For patients treated with every 3-week docetaxel at 75 mg/m2 and a starting ribociclib dose of
600 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
75 mg/m2
600 mg
-1
75 mg/m2
400 mg
-2
75 mg/m2
200 mg
-3
60 mg/m2
200 mg
For patients treated with every 3-week docetaxel at 75 mg/m2 and starting ribociclib dose of
400 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
75 mg/m2
400 mg
-1
75 mg/m2
200 mg
-2
60 mg/m2
200 mg


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For patients treated with every 3-week docetaxel at 75 mg/m2 and starting ribociclib dose of
200 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
75 mg/m
200 mg
-1
60 mg/m2
200 mg
For patients treated with every 3-week docetaxel at 60 mg/m2 and a starting ribociclib dose of
600 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
60 mg/m2
600 mg
-1
60 mg/m2
400 mg
-2
60 mg/m2
200 mg
-3
50 mg/m2
200 mg
For patients treated with every 3-week docetaxel at 60 mg/m2 and starting ribociclib dose of
400 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
60 mg/m2
400 mg
-1
60 mg/m2
300 mg
-2
60 mg/m2
200 mg
-3
                   50 mg/m2
200 mg
For patients treated with every 3-week docetaxel at 60 mg/m2 and starting ribociclib dose of
300 mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
60 mg/m2
300 mg
-1
60 mg/m2
200 mg
-2
50 mg/m2
200 mg
For patients treated with every 3-week docetaxel at 60 mg/m2 and starting ribociclib dose of
200 mg/day:


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Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
60 mg/m2
200 mg
-1
50 mg/m2
200 mg
For patients treated with weekly docetaxel and a starting ribociclib dose of 600 mg/day:
Dose Level
Weekly 
Docetaxel Dose
Ribociclib Daily Dose
1
30 mg/m2
600 mg
-1
30 mg/m2
400 mg
-2
30 mg/m2
200 mg
-3
25 mg/m2
200 mg
For patients treated with weekly docetaxel at 30 mg/m2 and starting ribociclib dose of 400 
mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
30 mg/m2
400 mg
-1
30 mg/m2
200 mg
-2
25 mg/m2
200 mg
For patients treated with weekly docetaxel at 30 mg/m2 and starting ribociclib dose of 200 
mg/day:
Dose Level
Every 3-Week 
Docetaxel Dose
Ribociclib Daily Dose
1
30 mg/m2
200 mg
-1
25 mg/m2
200 mg
5. The patient will be removed from protocol therapy for unacceptable toxicity if:
a.
There is a delay of treatment > 21 days for recovery from toxicity to permissible 
level
OR
b.
Patients require dose reduction below 200 mg/day of ribociclib plus 50 mg/m2 of 
every 3-week docetaxel (or below ribociclib 200 mg/day plus 25 mg/m2 weekly 
docetaxel) for treatment regimen-related toxicity.


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Note that patients removed from protocol therapy for toxicity will be followed on study 
until the time of progression or initiation of non-protocol therapy.
6. Dose modifications are made according to the system showing the greatest degree of 
toxicity.
7. Once a dose has been reduced for toxicity, it will not be re-escalated for an individual 
patient.
6.3.2.2
Treatment of hypersensitivity reactions to docetaxel
In case of hypersensitivity reactions, the investigator should institute treatment measures 
deemed medically appropriate per institutional guidelines. Based on prior experience with 
paclitaxel, the following treatment recommendations may be applicable. Investigator 
discretion should be taken regarding any additional measures to be instituted.
CTCAE Grade 1 Allergic Reaction/Hypersensitivity (transient rash, drug fever < 38 C):

Supervise at the bedside without further treatment. Consider decreasing rate of infusion 
until recovery from symptoms.
CTCAE Grade 2 Allergic Reaction/Hypersensitivity (urticaria, drug fever   38C):

Interrupt the infusion of docetaxel.

After recovery of symptoms, resume the infusion at a slower rate and if no further 
symptoms appear, complete the administration of the dose. If symptoms recur, discontinue 
infusion and follow guidelines below.
Recurrent CTCAE Grade 2 or CTCAE Grade 3 or 4 Allergic/Hypersensitivity Reactions:
Stop the infusion.
Administer additional doses of H1 and H2 blockers intravenously. Administer IV steroids 
(see discussion below) and consider epinephrine and bronchodilators as clinically indicated.
For recurrent grade 2 or grade 3 reactions, prior to rechallenge and with all subsequent 
cycles, consider both an H1 and H2 blocker intravenously plus dexamethasone 20 mg x 2 
doses (orally or intravenously) 12 and 6 hours pre docetaxel. Grade 4 reactions are 
considered severe hypersensitivity reactions, and rechallenge is contraindicated.
6.3.2.3
Dose Modifications for Hematologic Toxicity
Toxicity
Grade
Dose Adjustment for Docetaxel
Dose Adjustment for Ribociclib
Thrombocytopenia
1
≥75 x 109/L
No dose adjustment required.
No dose adjustment required.
2
50 x 109/L - <75 x
109/L
Day 1: Hold docetaxel until count is
> 75 x 109/L, then restart protocol 
therapy at same dose level.
Mid-cycle: No dose adjustment 
required.
Dose interruption 
until recovery to 
grade ≤1.
Re-initiate protocol 
therapy at the same 
dose level.
3 (without clinically 
significant bleeding) 
25 x 109/L - <50 x
109/L
Day 1: Hold 
docetaxel until count 
is > 75 x 109/L, then 
restart protocl 
therapy at one lower
Dose interruption 
until recovery to 
grade ≤1.
Re-initiate protocol 
therapy at the same


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dose level. If second 
dose reduction is 
required patient will 
be removed from 
protocol therapy.
Mid-cycle: No dose 
adjustment required
dose level.
• If toxicity recurs at grade 3: 
temporary dose interruption 
until recovery to grade ≤1 
and re-initiate protocol 
therapy at the next lower 
dose level.
Grade 3 with 
clinically significant 
bleeding
Day 1: Hold docetaxel until count
> 75 x 109/L and bleeding 
resolved, then restart protocol
therapy at one lower dose level.
Mid-cycle: Hold next docetaxel 
dose until count > 75 x 109/L and 
bleeding resolved, then restart
protocol therapy at one lower dose 
level.
If toxicity recurs (grade 3 
thrombocytopenia with clinically 
significant bleeding), discontinue 
protocol therapy.
Dose interruption until recovery to 
grade ≤1.
Re-initiate protocol therapy at the 
next lower dose level.
If toxicity recurs (grade 3 
thrombocytopenia with clinically 
significant bleeding), discontinue 
protocol therapy.
4
<25 x 109/L with or 
without bleeding.
Day 1: Hold docetaxel until count
> 75 x 109/L and bleeding
resolved, then restart protocol 
therapy at one lower dose level.
Mid-cycle: Hold next docetaxel 
dose until count > 75 x 109/L and
bleeding resolved, then administer 
protocol therapy at one lower dose 
level.
If a second dose reduction is 
required for docetaxel, patient will 
be removed from study therapy.
Dose interruption until recovery to 
grade ≤1.
Re-initiate protocol therapy at the 
next lower dose level.
• If toxicity recurs at grade 4: 
discontinue protocol therapy.
Absolute neutrophil 
count (ANC)
1
≥1.5 x 109/L
No dose adjustment required.
No dose adjustment required.
2
1.0 - <1.5 x 109/L
Day 1: Hold docetaxel until ANC
> 1.5 x 109/L, then restart
protocol therapy at same dose 
level.
Mid-cycle: No dose adjustment 
required.
No dose adjustment required.
3
0.5 - <1.0 x 109/L
Day 1: Hold docetaxel until ANC
> 1.5 x 109/L, then restart
protocol therapy at same dose 
level.
Mid-cycle: No dose 
adjustment required.
Dose interruption until 
recovery to >1.0 x 109/L.
Re-initiate protocol 
therapy at the same 
dose level.
• If toxicity recurs at grade 
3: temporary dose 
interruption until recovery 
to >1.0 x 109/L
• If resolved in ≤7 days, 
then maintain dose level.
• If resolved in >7 days, 
then re-initate protocol 
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dose level.
Filgrastim as clinically 
indicated.
4
<0.5 x 109/L
Day 1: Hold docetaxel 
until ANC > 1.5 x 109/L, 
then restart treatment at
the same dose level. If 
toxicity recurs at grade 4 
on day 1 of subsequent 
treatment cycle, hold 
docetaxel until ANC > 1.5
x 109/L, then restart at
one lower dose level.
Mid-cycle: No dose 
adjustment required.
Dose interruption until 
recovery to >1.0 x 109/L.
Re-initiate protocol 
therapy at the same 
dose level.
• If toxicity recurs at grade 
4: temporary dose
interruption until recovery 
to >1.0 x 109/L and re- 
initiate protocol therapy
at the next lower dose 
level.
Filgrastim as clinically 
indicated.
Febrile neutropenia
Grade 3 or 4
Hold docetaxel until ANC
> 1.5 x 109/L and no 
fever, then restart 
protocol therapy at one
lower dose level. For 
recurrent grade 3 or 4 
febrile neutropenia, 
discontinue protocol 
therapy.
Dose interruption until 
improvement of ANC ≥
1.1 x 109/L and no fever. 
Restart protocol therapy 
at the next lower dose 
level.
• If febrile neutropenia 
recurs, discontinue 
protocol therapy.
Anemia 
(Hemoglobin)
1
> 10 g/dL
No dose adjustment 
required.
No dose adjustment 
required.
2
8.0 – 10.0 g/dL
No dose adjustment 
required.
No dose adjustment 
required.
3
<8.0 g/dL
No dose adjustment 
required; transfuse as 
indicated.
Dose interruption until 
recovery to grade < 2; re- 
initiate ribociclib at the 
same dose level.
Transfuse as indicated.
4
Life-threatening 
consequences; 
urgent intervention 
indicated
Discontinue protocol 
therapy.
Discontinue protocol 
therapy.
6.3.2.4 Dose Modifications for Hepatic Toxicity
Patients who develop abnormal liver function tests as defined below, for any reason while on study, will 
have treatment held and/or reduced according to the following schedules:
HEPATOTOXICITY (BILIRUBIN, SGPT/ALT, SGOT/AST)
TOTAL BILIRUBIN without ALT/AST increase above baseline value
Grade 1 (> ULN – 1.5 x ULN)
Maintain ribociclib level with LFTs monitored bi-weekly
Hold docetaxel until total bilirubin improves to grade 0, then resume at 
one lower dose level.


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Grade 2 (> 1.5 – 3.0 x
ULN)
Interrupt dosing of ribociclib. If resolved to ≤ grade 1 in ≤ 21 days, 
then maintain current dose level. If resolved to ≤ grade 1 in > 21 days 
or toxicity recurs, then reduce 1 dose level. If toxicity recurs after two 
dose reductions, discontinue ribociclib.
Hold docetaxel until total bilirubin improves to grade 0, then resume at 
one lower dose level.
Grade 3 (> 3.0 – 10.0 x
ULN)
Interrupt dosing of ribociclib. If resolved to ≤ grade 1 in ≤ 21 days, 
lower 1 dose level of ribociclib. If resolved to ≤ grade 1 in > 21 days or 
toxicity recurs, discontinue ribociclib
Hold docetaxel until total bilirubin improves to grade 0, then resume at 
one lower dose level.  If toxicity recurs, discontinue docetaxel.
Grade 4 (> 10.0 x ULN) Discontinue ribociclib and docetaxel.
Confounding factors and/or alternative causes for increase of total bilirubin should be excluded before 
dose interruption/reduction. They include but are not limited to: evidence of obstruction, such as elevated 
ALP and GGT typical of gall bladder or bile duct disease, hyperbilirubinemia due to the indirect 
component only (i.e. direct bilirubin component ≤ 1 x ULN) due to hemolysis or Gilbert Syndrome, 
pharmacologic treatment, viral hepatitis, alcoholic or autoimmune hepatitis, other hepatotoxic drugs.
For patients with Gilbert Syndrome, these dose modifications apply to changes in direct bilirubin only. 
Bilirubin will be fractionated if elevated.
AST or ALT
AST or ALT without bilirubin elevation > 2 x ULN
Same grade as baseline or increase from 
baseline grade 0 to grade 1
No dose adjustment required with LFTs monitored 
per protocol if same grade as baseline or bi-weekly in 
case of increase from baseline grade 0 to 1.
Increase from baseline grade 0 or 1 to 
grade 2 (> 3.0
– 5.0 x ULN)
or
from baseline grade 2 to grade 3 (> 5.0 –
20.0 x ULN)
Interrupt dosing of ribociclib. If resolved to ≤ 
baseline value in ≤ 21 days, then maintain dose level. 
If resolved to ≤ baseline value in > 21 days or 
toxicity recurs, then reduce 1 dose level. If toxicity 
recurs after two dose reductions or recovery to ≤ 
baseline value is > 28 days, discontinue ribociclib.
Hold docetaxel until AST or ALT < grade 3, then 
resume at one lower dose level.
Increase from baseline grade 0 or 1 to 
grade 3 (> 5.0
– 20.0 x ULN)
Interrupt dosing of ribociclib until resolved to ≤ 
baseline value, then lower 1 dose level of ribociclib. 
If recovery to ≤ baseline value is > 28 days, 
discontinue
ribociclib. If toxicity recurs, discontinue ribociclib.
Hold docetaxel until AST or ALT < grade 3, then 
resume at one lower dose level.
Grade 4 (> 20.0 x ULN)
Discontinue ribociclib and docetaxel.


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AST or ALT and concurrent Bilirubin elevation
AST or ALT ≥ grade 2 (> 3 x ULN) in 
patients with normal values at baseline and total 
bilirubin  > 2 x ULN
or
AST or ALT ≥ grade 3 (> 5 x ULN) in 
patients with grade 1 or 2 at baseline, and total 
bilirubin  > 2 x ULN
Discontinue ribociclib.
Hold docetaxel until AST or ALT < grade 3 and 
total bilirubin grade 0, then resume at one lower 
dose level. If toxicity recurs, discontinue 
docetaxel.
Confounding factors and/or alternative causes for increased transaminases should be excluded before 
dose interruption/reduction. They include but are not limited to: concomitant medications, herbal 
preparations or dietary supplements, infection, hepato-biliary disorder or obstruction, new or progressive 
liver metastasis, and alcohol intake.
Additional follow-up for hepatic toxicities
Hepatic toxicity monitoring includes the following LFTs: albumin, ALT, AST, total bilirubin 
(fractionated if total bilirubin > 2 x ULN), alkaline phosphatase, and GGT. For patients with Gilbert 
Syndrome: total and direct bilirubin must  be  monitored,  intensified  monitoring  applies  to  changes 
in  direct bilirubin only.
Close observation is recommended in case of AST, ALT, and/or bilirubin increase requiring dose 
interruption, which involves:
•
Repeating liver enzyme and serum bilirubin tests two or three times weekly. Frequency of re- 
testing can decrease to once a week or less if abnormalities stabilize or return to normal values.
•
Obtaining a more detailed history of current symptoms.
•
Obtaining a more detailed history of prior and/or concurrent diseases.
•
Obtaining a history of concomitant drug use (including non-prescription medications, herbal and 
dietary supplements), alcohol use, recreational drug use, and special diets.
•
Ruling out acute viral hepatitis types A, B, C, D, and E; hepatotropic virus infections (CMV, 
EBV or HSV); autoimmune or alcoholic hepatitis; NASH; hypoxic/ischemic hepatopathy; and 
biliary tract disease.
•
Obtaining a history of exposure to environmental chemical agents.
•
Obtaining additional tests to evaluate liver function, as appropriate (e.g., INR, direct bilirubin).
•
Considering gastroenterology or hepatology consultations.
•
Assessing cardiovascular dysfunction or impaired liver oxygenation, including hypotension or 
right heart failure as possible etiologies for liver dysfunction.
6.3.2.5
Cardiovascular
Dose modification of ribociclib in case of QT prolongation will be as follows:
Grade
Dose Modification
For all grades
1.
Check the quality of the ECG.
2.
Perform analysis of serum electrolytes (K+, Ca++, 
Phos, Mg++). If below the lower limit of normal, 
interrupt ribociclib administration, correct with


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supplements or appropriate therapy as soon as 
possible, and repeat electrolytes until documented as 
normal.
3.
Review concomitant medication usage for the potential 
to inhibit CYP3A4 and/or to prolong the QT interval.
4.
Check compliance with correct dose and administration 
of ribociclib.
1
QTc 450-480 ms
Perform steps 1-4 as directed in “For All Grades.” No 
dose adjustment required.
2
QTc 481-500 ms
Interrupt ribociclib. Perform steps 1-4 as directed “For All 
Grades.”
Perform a repeat ECG one hour after the first QTcF of
≥418ms.
Repeat ECG as clinically indicated until the QTcF returns 
to < 481 ms, Restart ribociclib with dose reduced by 1 
dose level. Refer to Section 6.3.2.1 for dosing schedule.
If QTcF ≥ 481 ms recurs, ribociclib should be reduced 
again by 1 dose level.
Repeat ECGs 7 days and 14 days after dose resumption 
(then as clinically indicated) for any patient who has 
therapy interrupted due to QTcF ≥481 ms
3
QTc ≥ 501 ms on at least two separate ECGs
Interrupt ribociclib. Perform steps 1-4 as directed in “For 
All Grades.”
• Consider consulting a local central cardiologist to perform 
a repeat ECG one hour after the first QTcF of > 501 ms.
• If QTcF remains ≥ 501 ms, repeat ECG as clinically 
indicated, but at least once a day until the QTcF returns to < 
481 ms.
• If QTcF returns to < 481 ms, ribociclib should be reduced 
by 1 dose level.

If QTcF remains ≥ 481 ms after performing steps 1-4 as 
directed in “For All Grades,” discontinue ribociclib.
Repeat ECGs 7 days and 14 days after dose 
resumption for any patient who has therapy interrupted 
due to QTcF > 501 ms
• If QTcF of ≥ 501 ms recurs, discontinue ribociclib
4
QT/QTc ≥ 501 or > 60 ms change from 
baseline
and
Torsades de pointes or polymorphic 
ventricular tachycardia, or signs/symptoms of 
serious arrhythmia
Discontinue ribociclib. Perform steps 1-4 as directed in 
“For All Grades.”
•
Obtain local cardiologist consultation
•
Perform a repeat ECG one hour after the first QTcF of
≥501 ms
•
If QTcF remains ≥501 ms, repeat ECG as clinically 
indicated, but at least once a day until the QTcF 
6.3.2.6 Hypersensitivity infusion reaction.


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No dose reductions should be made. Acute hypersensitivity reactions related to docetaxel infusion 
should be managed according to Section 6.3.2.2.


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6.3.2.7 All other adverse reactions
For treatment regimen-related toxicities > grade 3 (excluding the hematologic, liver, and cardiac 
toxicities outlined above, as well as grade 3 nausea/vomiting/diarrhea/fatigue lasting less than 48 
hours with optimal medical management, any grade alopecia, or non-clinically significant 
laboratory abnormalities that resolve within 48 hours with optimal medical management), both 
drugs should be withheld until resolution to < grade 1 (or to baseline if baseline was greater than 
grade 1). Treatment may be restarted at next lower dose level if the toxicity improves to grade 1 
or lower within 2 weeks of onset of adverse event. If toxicity recurs at grade 3 or higher, patients 
will be required to discontinue study therapy.
Ribociclib should be held for grade 2 related toxicities and restarted at the original dose level 
once recovered to grade ≤ 1. If the same toxicity recurs at grade 2, interrupt ribociclib until 
recovery to grade ≤ 1, then restart ribociclib at the next lower dose level.
Toxicities solely related to corticosteroid use (hyperglycemia, insomnia, hypertension, etc.) and 
androgen deprivation therapy (hot flashes, gynecomastia, erectile dysfunction, etc.) will not 
require mandatory dose reduction.  Treating physicians may modify the doses of prednisone 
as clinically indicated. Cessation of prednisone therapy is not a reason to remove a patient from 
protocol therapy or to be considered a DLT.
6.4
Cycle Delays
Initiation of subsequent cycles may be delayed for a maximum of three weeks for toxicity or at the 
discretion of the treating physician. Any patient who fails to recover from a treatment related toxicity to 
baseline or Grade 1 within 21 days of scheduled retreatment will be removed from the study and followed 
for progression or initiation of non-protocol therapy.
6.5
Duration of Therapy
In the absence of treatment delays due to toxicity(ies), treatment may continue until one of the following 
criteria applies:

Disease progression (see Section 8)

Unacceptable toxicity according to above definition (Section 6.3.2.1)

Patient withdrawal from study

Study closure
When a patient is discontinued from the study, the reason(s) for discontinuation should be documented. 
Follow-up should be maintained every three months until progression or initiation of non-protocol 
therapy. Patients who experienced any drug-related toxic effects will be followed at least every four 
weeks until all study drug-related toxicities resolve, stabilize, return to baseline, or are deemed 
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7
DRUG INFORMATION (adapted from the Investigators Brochure and package insert)
7.1
Docetaxel
Classification and Mode of Action
Docetaxel is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis 
beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical 
name for docetaxel is (2R,3S)-N-carboxy-3-phenylisoserine,N-tert-butyl ester, 13-ester with 5β-20- 
epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate, trihydrate.
Preparation and Administration:
TAXOTERE Injection Concentrate (20 mg/mL) requires NO prior dilution with a diluent and is ready 
to add to the infusion solution. Use only a 21 gauge needle to withdraw TAXOTERE from the vial 
because larger bore needles (e.g., 18 and 19 gauge) may result in stopper coring and rubber 
particulates.
1.
TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored
under refrigeration, allow the appropriate number of vials of TAXOTERE Injection Concentrate 
vials to stand at room temperature for approximately 5 minutes before use.
2.
Using only a 21 gauge needle, aseptically withdraw the required amount of TAXOTERE 
injection concentrate (20 mg docetaxel/mL) with a calibrated syringe and inject via a single 
injection (one shot) into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution 
or 5% Dextrose solution to produce a final concentration of 0.3 mg/mL to 0.74 mg/mL. If a dose 
greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so 
that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.
3.
Thoroughly mix the infusion by gentle manual rotation.
4.
As with all parenteral products, TAXOTERE should be inspected visually for particulate matter 
or discoloration prior to administration whenever the solution and container permit. If the 
TAXOTERE dilution for intravenous infusion is not clear or appears to have precipitation, it 
should be discarded.
5.
TAXOTERE infusion solution is supersaturated, therefore may crystallize over time. If crystals 
appear, the solution must no longer be used and shall be discarded.
The TAXOTERE dilution for infusion should be administered intravenously as a 1-hour infusion 
under ambient room temperature (below 25°C) and lighting conditions.
How Supplied
Docetaxel will be obtained via manufacturer via commercial insurance. 
Potential Drug Interactions
Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel 
may be modified by the concomitant administration of compounds that induce, inhibit, or are 
metabolized by cytochrome P450 3A4.
In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was 
coadministered with ketoconazole, a potent inhibitor of CYP3A4. Protease inhibitors, particularly 
ritonavir, may increase the exposure of docetaxel. Concomitant use of TAXOTERE and drugs 
that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. In patients


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receiving treatment with TAXOTERE, close monitoring for toxicity and a TAXOTERE dose 
reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be 
avoided [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].
7.2
Ribociclib
Classification and Mode of Action:
Ribociclib inhibits the CDK4/CCND1 and CDK6/cyclin-D3 enzyme comples (IC50  values of
0.01 and 0.039 micromolar concentration respectively).
Nomenclature: 7-Cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H- 
pyrrolo[2,3-d] pyrimidine-6-carboxamide succinate (1:1)
Molecular formula 
C23H30N8O.C4H6O4
Relative molecular mass 
Free base: 434.54
Salt form: 552.63
Physical state
Light tan to yellow powder
How Supplied
The ribociclib drug product is planned for oral administration. The available clinical forms are 
hard gelatin capsules (50 mg and 200 mg), and film-coated tablets (200 mg) 
The shelf life of the drug product is established based on ongoing stability studies and may be 
extended during the clinical study. The film-coated tablets are stored in HDPE bottles with 
induction seals and child resistant polypropylene caps.
Ribociclib is a potent investigational new drug that has not been fully evaluated. Exercise 
appropriate hygiene and clinical practice precautions.
Availability
Ribociclib will be supplied by Novartis or its designee as 50 mg or 200 mg film-coated tablets.
Packaging and labeling
Study Treatment
Packaging
Labeling
Ribociclib (ribociclib)
Film-coated tablets in 
bottles
Labeled as ‘Ribociclib’ 
or ‘LEE011’


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Drug Supply and Storage
Study treatments must be received by designated personnel at the study site, handled and stored safely 
and properly, and kept in a secured location to which only the investigator and designated site personnel 
have access. Upon receipt, the study treatment should be stored according to the instructions specified on 
the drug labels and in the Investigator’s Brochure.
Supply and storage of study treatment
Study Treatment
Supply
Storage
Ribociclib
Bulk supplied by Novartis
Refer to study treatment 
label
Drug Administration
Ribociclib should be administered as a flat-fixed dose, and not by body weight or body surface area. 
Patients must should be instructed to return unused study drugs to the site at the discontinuation or 
completion of treatment.
Ribociclib must be taken as follows:

Patients should be instructed to take the ribociclib capsules with a large glass of water (~ 250 mL) 
at the same time each day.

Ribociclib can be taken without regard to meals; however dietary habits around the time of 
dosing should be as consistent as possible throughout the study

Patients should be instructed to swallow ribociclib capsules whole and not to chew, crush, or 
open them

If vomiting occurs during the course of treatment, no re-dosing of the patient is allowed before 
the next scheduled dose

Any doses that are missed (not taken within 6 hours of the intended time) should be skipped and 
should not be replaced or made up on a subsequent day

Patients must avoid consumption of grapefruit, Seville oranges or products containing the juice of 
each during the entire study and preferably 7 days before the first dose of study medication, due 
to potential CYP3A4 interaction with the study medications. Orange juice is allowed
Study drug compliance
Compliance will be assessed by the investigator and/or study personnel at each patient visit and 
information provided by the patient and/or caregiver. Records of study medication used, dosages 
administered, and intervals between visits and the completion of the study will be captured in the Drug 
Accountability Form. This information must be captured in the source document at each patient visit. 
On PK sampling days, compliance will be assured by administration of the study treatment under the 
supervision of investigator or his/her designee, and will be verified by determination of ribociclib in 
plasma.
Study drug accountability
The investigator or designee must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log.


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Disposal and destruction
The study drug supply can be destroyed at the local Novartis facility, Drug Supply group or third party, as 
appropriate. Study drug destruction at the investigational site will only be permitted if authorized by 
Novartis in a prior agreement and if permitted by local regulations.
Human Toxicology:
As of 2 July 2013, 78 patients have been treated with increasing doses of ribociclib orally, once 
daily for 21 days followed by a 1 week rest (28-day cycle). Doses ranging from the starting dose 
of 50 mg to 1200 mg were evaluated on this schedule. In addition, continuous dosing of ribociclib 
at 600 mg was evaluated (once daily for 28 days of a 28-day cycle). A total of 10 events meeting 
DLT criteria were observed at the indicated doses and include grade 3 mucositis/stomatitis (n=1) 
at 50 mg, grade 3 pulmonary embolism (n=1) at 280 mg, grade 3 hyponatremia (n=1) and 
prolonged grade 3/4 neutropenia (n=1) at 400 mg, prolonged grade 2 elevated creatinine (n=1) at 
600 mg, grade 4 thrombocytopenia (n=1) at 750 mg, grade 3 asymptomatic QTcF prolongation 
with grade 3 neutropenia (n=1) at 900 mg and grade 4 febrile neutropenia (n=1) and grade 4 
thrombocytopenia (n=1) at 1200 mg. There was also 1 DLT, grade 3 neutropenia (n=1) at 600 mg 
on the continuous dosing schedule. Grade 1/2 neutropenia was observed at doses of 280 mg or 
higher (23%) and grade 3/4 neutropenia was seen at doses of 400 mg and higher (21%).
Asymptomatic grade 2 QTc prolongation was observed with increasing frequency starting at 
600 mg with grade 3 prolongation in 2 patients. The most frequently reported AEs (> 15%) 
regardless of study treatment relationship include neutropenia (44%), nausea (42%), anemia 
(41%), leukopenia (37%), fatigue (35%), diarrhea (31%), thrombocytopenia (28%), vomiting
(28%), lymphopenia (27%), decreased appetite (24%), asthenia (23%), constipation (19%),
hyperglycemia (17%), and hypoalbuminemia (17%).
The majority of all reported adverse events were mild or moderate (grade 1-2) and reversible. 
There have been no reported deaths related to single agent ribociclib. One treatment-related death 
due to intracranial hemorrhage was reported in study CMEK162X2114, where ribociclib was 
administered in combination with binimetinib (MEK162).
Additional Dosing Guidelines for Pharmacokinetic Sampling / ECG / Chemistry panel / Lipid Panel 
Collection
On days with PK, ECG sampling, chemistry panel and/or lipid panel sampling, the following additional 
guidelines should be followed:
•
On a day when PK blood collection is scheduled at the clinic, patients must take study treatment 
in the clinic under the supervision of the Investigator or designee. On all other days patients may 
take the study treatment at home.
•
Pre-dose samples should be drawn prior to dosing. The sampling time of the PK samples and the 
dosing time must be precisely recorded in the CRF. Furthermore, the dosing date and time the 
study medication was taken on the day before the PK assessment must be precisely recorded in 
the CRF.
•
Post-dose PK samples should be collected after dosing of the study treatment.


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7.3
Prednisone:
Pharmacology
Glucocorticoids are quickly and completely absorbed from the GI tract.
Formulation
Refer to package insert.
Storage and stability
Prednisone should be stored at room temperature.
Administration
Prednisone is administered orally.
Availability
Prednisone is commercially available, and commercial sources will be used.
Contraindications
Corticosteroids should be used cautiously in patients with hypothyroidism, cirrhosis, ocular herpes 
simplex, existing emotional instability or psychotic tendencies, nonspecific ulcerative colitis, 
diverticulosis, fresh intestinal anastamoses, peptic ulcer, renal insufficiency, hypertension, 
osteoporosis, and myasthenia gravis. Immunization procedures (especially smallpox) should not be 
undertaken in patients on corticosteroids.
Human toxicology
Adverse affects associated with prednisone use are: fluid and electrolyte disturbances, congestive 
heart failure in susceptible persons, hypertension, euphoria, personality changes, insomnia, mood 
swings, depression, worsening of infection (i.e., tuberculosis), exacerbation or symptoms of diabetes, 
psychosis, muscle weakness, osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, 
peptic ulcer, dermatologic disturbances, convulsions, vertigo, headache, endocrine abnormalities, 
ophthalmic changes, and metabolic changes. Some patients have experienced itching and other 
allergic, anaphylactic or hypersensitivity reactions. Withdrawal from prolonged therapy may result in 
symptoms including fever, myalgia, and arthralgia. Phenytoin, phenobarbital, and ephedrine increase 
metabolic clearance of corticosteroids.
Further information about prednisone can be found in the manufacturer’s package insert.
7.4
Filgrastim
(Adapted from package insert- please see package insert for further details)
Formulation
Filgrastim is a 175 amino acid protein manufactured by recombinant DNA technology. It has a 
molecular weight of 18,800 daltons. It is a sterile, clear, colorless, preservative-free liquid available


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for parenteral administration. The product is available in single use vials and prefilled syringes 
containing either 300 mcg or 480 mcg.
Pharmacokinetics
The half-life of filgrastim is approximately 3.5 hours. It is systemically degraded.
Adverse Events
Filgrastim is contraindicated in patients with known hypersensitivity to E coli-derived proteins‚ 
pegfilgrastim‚ filgrastim, or any other component of the product. Rare cases of splenic rupture have 
been reported following the administration of filgrastim. Patients who report left upper abdominal 
pain and/or shoulder tip pain should be evaluated for an enlarged spleen or splenic rupture.
Allergic reactions to filgrastim, including anaphylaxis, skin rash, and urticaria, have been reported in 
postmarketing experience. The majority of reported events occurred upon initial exposure. In some 
cases, symptoms recurred with rechallenge, suggesting a causal relationship. In rare cases, allergic 
reactions including anaphylaxis, recurred within days after initial anti-allergic treatment was 
discontinued. If a serious allergic reaction occurs, appropriate therapy should be administered, with 
close patient follow-up over several days. Filgrastim should be permanently discontinued in patients 
with serious allergic reactions.
In the placebo-controlled trials, more common adverse events included pyrexia, bone pain, rash, 
cough, and dyspnea.
Cytopenias resulting from an antibody response to exogenous growth factors have been reported on 
rare occasions in patients treated with other recombinant growth factors. There is a theoretical 
possibility that an antibody directed against filgrastim may cross-react with endogenous G-CSF, 
resulting in immune-mediated neutropenia, but this has not been observed in clinical studies.
Dosage and Administration
The recommended dosage of filgrastim are daily subcutaneous injections of 300 or 480 mcg 
depending upon body weight.
Storage and Stability
Filgrastim should be stored at 2 to 8 degrees Celsius in the carton to protect from light.


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8
MEASUREMENT OF RESPONSE
8.1
Measurement of response in patients with measurable disease
Response and progression will be evaluated in this study using the international criteria proposed by the 
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.13 Changes in only the longest 
diameter (unidimensional measurement- LD) of the tumor lesions are used in the RECIST criteria.
Note: lesions are either measurable or non-measurable using the criteria provided below. 
The term “evaluable” in reference to measurability will not be used because it does not 
provide additional meaning or accuracy. All measurements should be taken and recorded 
in metric notation using a ruler or calipers. All Screening evaluations should be 
performed as closely as possible to the beginning of treatment and never more than 30 
days before the beginning of the treatment. The same method of assessment and the 
same technique should be used to characterize each identified and reported lesion at 
baseline and during follow-up. Imaging-based evaluation is preferred to evaluation by 
clinical examination when both methods have been used to assess the antitumor effect of 
a treatment.
Clinical lesions. Clinical lesions will only be considered measurable when they are superficial (e.g., skin 
nodules and palpable lymph nodes). In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended.
Chest x-ray. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined 
and surrounded by aerated lung. However, CT is preferable.
Conventional CT and MRI. These techniques should be performed with cuts of 10 mm or less in slice 
thickness contiguously. Spiral CT should be performed using a 5 mm contiguous reconstruction 
algorithm. This applies to tumors of the chest, abdomen, and pelvis. Head and neck tumors and those of 
extremities usually require specific protocols.
8.1.1
Measurable disease/ Target lesions
All measurable lesions (lesions that can be accurately measured in at least one dimension [longest 
diameter to be recorded] as ≥10mm with spiral CT) up to a maximum of 2 lesions per organ and 5 
lesions total, representative of all involved organs, should be identified as target lesions and 
recorded and measured at Screening. Target lesions should be selected on the basis of their size 
(lesions with the longest diameter) and the suitability for accurate repeated measurements (either 
by imaging techniques or clinically). A sum of the longest diameter (LD) for all target lesions 
will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as a 
reference by which to characterize the objective tumor response.
Lymph node metastases must measure 1.5 cm or greater in short axis diameter to be considered 
target lesions, while other target lesions must measure 1 cm or greater (with spiral CT scans).17
Complete Response (CR):
Disappearance of all target lesions
Partial Response (PR):
At least a 30% decrease in the sum of the longest 
diameter (LD) of target lesions, taking as reference the 
baseline sum LD
Progressive Disease (PD):
At least a 20% increase in the sum of the LD of target


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lesions, taking as reference the smallest sum LD
recorded since the treatment started (including 
baseline LD), or the appearance of one or more new 
lesions
Stable Disease (SD):
Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD, taking as 
reference the smallest sum LD since the treatment 
started (including baseline LD)
8.1.2
Evaluation of non-target lesions
Complete Response (CR):
Disappearance of all non-target lesions and
normalization of tumor marker level
Incomplete Response/ 
Stable Disease (SD):
Persistence of one or more non-target lesion(s), and/or 
maintenance of tumor marker level above the normal 
limits
Progressive Disease (PD):
Appearance of one or more new lesions, and/or 
unequivocal progression of existing non-target lesions
Although a clear progression of non-target lesions only is exceptional, in such circumstances, the 
opinion of the treating physician should prevail and the progression status should be confirmed 
later on by the study chair.
8.1.3
Evaluation of best overall response
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started, including baseline; see table below). The 
patient's best response assignment will depend on the achievement of both measurement and 
confirmation criteria.
8.1.4
Confirmation
To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by 
repeat studies no less than 4 weeks after the criteria for response are first met. In the case of SD, 
follow-up measurements must have met the SD criteria at least once after study entry at a 
minimum of 12 weeks after study entry.
8.1.5
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are met for 
CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started). The duration of overall complete response is measured from 
the time measurement criteria are first met for CR until the first date that recurrent disease is 
objectively documented.


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Target Lesions
Non-Target Lesions
New Lesions
Response
CR
CR
No
CR
CR
Incomplete response/SD
No
PR
PR
Non-PD
No
PR
SD
Non-PD
No
SD
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
8.2
Evaluation of non-measurable bone disease 17
Bone scans obtained after the Screening evaluation will be used to evaluate post-treatment changes. 
Bone scans obtained will be evaluated as either “no new lesions” or “new lesions” on the tumor 
measurement forms.
a.
For the first scheduled reassessment: New lesions at the first scheduled evaluation (9 weeks) will 
require a confirmatory bone scan 6 or more weeks later. If no new lesions are observed on the 
confirmatory bone scan, study therapy is continued. If additional new lesions are observed, then 
the patient has experienced progression. Progression in this situation is dated as the time of the 
first reassessment scan.
b.
For subsequent scheduled reassessments: If no new lesions are observed, study therapy will 
continue. If new lesions are observed, this is evidence of disease progression. Date of progression 
is the date at which the scan was obtained.
8.3
Post-treatment PSA Changes
All patients, with or without measurable or non-measurable disease, will be evaluated for PSA decline. 
Patients with disease that is not measurable will be eligible for this study and will be assessed for 
response based on changes in PSA and serial bone scans (if appropriate). The baseline serum PSA must 
be at least 2 ng/mL. Patients who show PSA increases will not be evaluated for PSA progression prior to 
12 weeks of study therapy.
a.
30% and 50% PSA Decline: PSA decline of at least 30% and 50%, respectively, from baseline 
confirmed by a second measurement at least 3 weeks later. The reference for these declines 
should be a PSA measured within 2 weeks prior to starting therapy.
b.
PSA Progression: Prostate Cancer Working Group 2 (PCWG2) Criteria will be reported. PSA 
progression occurs when the PSA has increased 25% or greater above nadir and an absolute 
increase of 2 ng/mL or more from the nadir is documented. Where no decline is observed, PSA 
progression similarly occurs when a 25% increase from baseline value along with an increase in 
absolute value of 2 ng/mL or more. Patients will receive a minimum of 12 weeks of therapy prior 
to being evaluable for this endpoint. PSA progression (without evidence of progression on scans) 
will not be criteria for discontinuation of study therapy.
c.
PSA Response Duration: The PSA response duration commences on the date of the first 50% 
decline in PSA. The response duration ends when the PSA value increases by 25% above the 
nadir, provided that the increase in the absolute-value PSA level is at least 5 ng/mL or back to 
baseline, whichever is lower.


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d.
Progressive Disease by PSA (as defined by PSA Progression, above)
e.
Time to PSA Progression: The start of the time to PSA progression is the day treatment is 
initiated. The end date is the date of the first PSA rise over the determined PSA PD value.
8.4
Progressive disease (PD)
Progressive disease will be defined by any one of the following:
1.
Appearance of new metastatic lesions outside the bone
2.
New metastatic lesions on bone scan confirmed as described above
3.
Development of an indication for radiotherapy while on treatment
4.
Unequivocal progression of non-target lesions
5.
Global deterioration of health status requiring discontinuation of treatment without objective 
evidence of disease progression
Note that PSA progression (as defined above) alone does not meet the criteria for progressive 
disease.


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9
STATISTICAL CONSIDERATIONS
9.1
Study Design
This is a phase 1b/II open-label study evaluating the combination of docetaxel, prednisone, and ribociclib 
in patients with metastatic castration resistant prostate cancer and evidence of prior progression on 
abiraterone, enzalutamide, ARN-509, or the combination. The phase 2 study will be a single arm two 
stage design evaluating the radiographic progression-free survival rate at 6 months with the treatment 
combination.
9.2
Determination of Sample Size and Study Power
The anticipated sample size of the phase 1b portion of the study is 9-18 patients. There will be up to three 
dose levels evaluated using standard 3+3 dose escalation schema. At least 6 patients must be treated at a 
given dose level to declare MTD. These 6 patients will be counted towards the first stage of the phase 2 
study. 
The sample size of the phase 2 portion of the study is based upon the anticipated radiographic 
progression-free survival probability after 6 months of protocol therapy. Based upon prior studies with 
docetaxel monotherapy, this is estimated to be 35%, accounting for the high-risk features (post 
abiraterone and/or enzalutamide) of this study cohort. A PFS rate at 6 months of 55% would justify 
further study of the treatment combination. 17 patients will be enrolled during the first stage of the phase 
2 study. If at least 7 patients are free of radiographic progression at 6 months, 12 additional patients will 
be enrolled. If at least 14 patients are progression free at 6 months, the null hypothesis of a 35% PSA 
progression-free survival rate will be rejected. This design has 80% power with unidirectional level of 
significance of 0.1 to detect this magnitude of effect size. The study design has 62% probability of 
stopping early if the 6 months progression free rate is 35% or less and a 8% probability of early stopping 
if the progression free rate is 55% or more.
9.3
Accrual
For the Phase 1b portion of the study, it is estimated that approximately 2 patients per month will be 
enrolled, and that the recommended phase 2 dose of ribociclib will be established 12 months after first 
patient enrolled. During the Phase 2 portion of the study, it is estimated that approximately 2 patients per 
month will be enrolled, leading to an estimated accrual period during phase 2 of approximately 15 
months.
9.4
Interim Analyses
During the phase 1b portion of the study, if dose level IB (weekly docetaxel 30 mg/m2 in combination 
with ribociclib 200 mg/day) is declared a non-tolerable dose, the study will close to further accrual.
During phase 2, an interim analysis for safety and efficacy will be conducted after 17 evaluable patients 
have been enrolled. If six or more patients experience toxicity meeting the definition of dose-limiting 
toxicity, study accrual will be halted and alternative dosing schema may be pursued. If less than 7 out of 
the first 17 patients enrolled are radiographically free of progression 6 months from the start of protocol 
therapy, the study will halt accrual and alternative dosing schema may be pursued.
9.5
Analysis Population
Subject disposition and all efficacy endpoints will be assessed using data from the intent-to-treat 
population. Safety analysis will include all patients who receive at least one dose of protocol therapy.


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9.6
Demographics and Baseline Characteristics
Demographic variables will include age, race, ethnicity, and baseline height and weight. Additional 
disease specific features will be captured on electronic case report form, including:

Gleason grade at the time of diagnosis

Year of prostate cancer diagnosis

Extent of disease at the time of study entry (nodal, bone, visceral metastases (lung, liver, or 
both)).

Duration of response to primary androgen deprivation therapy

Type of resistance to prior abiraterone/enzalutamide/ARN-509 (primary = no PSA decline or 
radiographic response; secondary = all others)

Prior chemotherapy in the hormone-naïve setting (yes/no), and if yes, date of last chemotherapy 
administration
9.7
Study Endpoints 
9.7.1 
Primary Endpoints
Phase 1b: Maximally tolerated dose and recommended phase 2 dose of ribociclib in combination with 
docetaxel plus prednisone, based upon evaluation of dose-limiting toxicities and adverse events measured 
using Common Toxicity Criteria version 4.03
Phase 2: Radiographic progression-free survival rate at 6 months from start of protocol therapy.
9.7.2 
Secondary Endpoints:

Median radiographic progression-free survival

Objective response rate and median duration of response using RECIST 1.1 criteria, among 
patients with measurable disease at baseline

PSA progression-free survival (defined in Section 8)

PSA response rate (defined in Section 8)

Adverse events of the treatment combination using Common Toxicity Criteria version 4.03

Pharmacokinetic profile of ribociclib when given following administration of docetaxel and with 
concurrent prednisone use. PK parameters to be measured include estimated Cmax, AUC0-24, 
and Css.
9.7.3 
Exploratory Endpoints:

Association between clinical outcomes on ribociclib plus docetaxel with baseline and percent 
change from baseline in SUVmax-ave on gallium citrate PET/CT (Optional - UCSF Patients 
Only)

Association between clinical outcomes and genomic markers of MYC/cell-cycle pathway, 
including MYC amplification/overexpression, validated MYC gene expression signature score, 
Rb1 deletion, CDK4/6 and cyclin D overexpression, assessed via metastatic tumor biopsy and 
CTCs and cell-free ctDNA

Pathway signature of clinical, genomic, and proteomic factors predicting sensitivity to treatment 
combination using an unbiased approach with DiPSC bioinformatics tool


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9.8
Methods for Analysis
9.8.1 Analytic plan for the primary study endpoints
The maximum tolerated dose and recommended phase 2 dose of ribociclib in combination with docetaxel 
and prednisone will be determined using criteria outlined in Section 6. The frequency and severity of 
adverse events will be reported in descriptive fashion.
For the phase 2 portion of the study, the radiographic progression-free survival rate at 6 months and 
median radiographic progression-free survival will be estimated using the Kaplan-Meier product limit 
method. Durations will be measured from day 1 of study treatment to first date of radiographic 
progression or death, whichever occurs sooner. Patients who discontinue study therapy for toxicity, 
withdrawal from study, or PSA-only progression, will be censored at the date of last radiographic tumor 
assessment for this analysis. Patients who discontinue therapy for evidence of clinical progression/clinical 
deterioration will be included in this analysis.
9.8.2 Analytic plan for the secondary study endpoints
For patients with measurable disease at baseline, the objective response rate will be descriptively 
reported. Among patients with objective response, the median duration of response will be estimated 
using the criteria outlined in Section 8.1.5.
The proportion of patients with greater than 50% decline from baseline in serum PSA will be reported in 
descriptive fashion. The probability distribution of the median time to PSA progression will be estimated 
using the Kaplan-Meier product limit method. Durations will be measured from day 1 of study treatment 
to first date of PSA progression, as defined in Section 8. Patients who discontinue study therapy prior to 
PSA progression will be censored at the date of last PSA assessment while receiving protocol therapy.
The incidence and severity of adverse events related to treatment regimen will be descriptively reported 
using Common Toxicity Criteria version 4.03.
The estimated AUC0-24hr, Cmax, and Cstead-state serum concentration of ribociclib will be reported using 
descriptive statistics.
9.8.3 Analytic plan for the exploratory study endpoints
 Gallium citrate PET imaging (Optional - UCSF Patients Only):
A trained nuclear medicine physician blinded to the clinical outcomes of the patients will evaluate the 
reconstructed PET, CT, and fused PET/CT images using a PET volume computer-assisted reading 
software package. A positive lesion on gallium citrate PET will be defined as a focus of activity with at 
least 1.5 times higher SUV compared with mediastinal blood pool that is not attributable to  other 
etiologies of tracer distribution (e.g. inflammation, excretion). A volume of interest (VOI) will be 
semiautomatically placed around each lesion, and the calculated maximum standard uptake value 
(SUVmax) will be recorded for each lesion. Adjusted SUVmax data will then be averaged across all 
lesions within a given patient (SUVmax-avg). In order to avoid clustering effects, analysis will be limited 
to the five largest osseous metastases and all visceral metastases.
For the purposes of analyzing the association between SUVmax-ave and percent change from baseline on 
the paired scans respectively with subsequent clinical outcomes, the phase 2 cohort will be dichotomized 
into those with SUVmax-ave values above and below the median. The dichotomized subgroups will be 
compared with respect to objective response rate and PSA response proportion using Fisher’s exact test, 
and the log-rank test will be used to compare dichotomized groups with respect to radiographic 
progression-free survival and time to PSA progression.


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Genomic predictors of response:
MYC amplification, overexpression, and signature score using a validated MYC expression signature, 
along with other markers of MYC/cell cycle proliferation, including Rb1 copy number/mutation status, 
CDK4/6 and cyclin D/E expression, will be ascertained using metastatic tumor biopsy, and whenever 
possible, from concurrent analysis of CTCs and cell-free ctDNA. The association between these 
variables and clinical outcomes will be performed using Fisher’s exact test for categorical variables and 
Mann-Whitney test for continuous variables.
No adjustment for multiple comparisons will be made for this exploratory study analysis. 
DiPSC-generated signature of response:
The study cohort will be dichotomized into those with either objective tumor response or clinical benefit 
from combination therapy (stable disease or greater for more than 6 months) versus those that do not have 
clinical benefit. The DiPSC tool integrates all measured clinical, genomic, and proteomic factors in an 
unbiased manner to determine those factors most tightly correlated with clinical benefit/response or 
resistance to protocol therapy. Those factors will be utilized to develop a ‘signature’ of benefit from 
taxane + CDK4/6 inhibitor combination therapy.


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10
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
U.S. regulations require that a sponsor reports Serious Adverse Events (SAEs) occurring with use of its 
product in a clinical trial if it is unexpected and felt to be related to use of the drug. All SAEs that occur 
will be evaluated by the site investigator and confirmed by the Lead Site Sponsor/Investigator for 
reportability to FDA. The PCCTC will facilitate this evaluation with the site investigator and Lead Site 
Sponsor/Investigator. An Adverse Event should be identified, Serious Adverse Event and Expectedness 
determined and causality assessed by the investigator using the definitions that follow.
10.1
Definitions
An Adverse Event (AE) is any untoward medical occurrence in a patient administered a pharmaceutical 
product and which does not necessarily have to have a causal relationship with the treatment.
A Serious Adverse Event (SAE) is an adverse event occurring at any dose that results in any of the 
following outcomes:
a.
Death
b.
Life-threatening1
c.
Persistent or significant disability/incapacity2
d.
In patient hospitalization or prolongation of existing hospitalization
e.
Congenital anomaly/birth defect
1 The term "life-threatening" in the definition of "serious" refers to an event in which in the view of the 
initial reporter the patient was at immediate risk of death from the adverse experience as it occurred; it 
does not refer to an event which had it occurred in a more severe form, might have caused death.
2 A substantial disruption of a person’s ability to conduct normal life functions.
An event may not meet any of the above seriousness criteria but still be judged as medically serious. That 
is, important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered a serious adverse drug experience when based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one 
of the outcomes (a-e) listed above.  Some examples of this type of event are:

blood dyscrasia without inpatient hospitalization

convulsions without inpatient hospitalization

intensive treatment in an emergency room or at home for allergic bronchospasm without inpatient 
hospitalization

development of drug dependency

drug abuse

overdose with an associated serious event, or required intervention to prevent impairment/damage
An Unexpected Adverse Event is not listed in the current US Package Insert (USPI) or an event that 
may be mentioned in the USPI, but differs from the event because of greater severity or specificity.
Causality is a determination of whether there is a reasonable possibility that the drug may have caused or 
contributed to an adverse event. It includes assessing temporal relationships dechallenge/rechallenge 
information, association (or lack of association) with underlying diseases, and the presence (or absence) 
or a lack of one or more likely causes.
The Investigator must determine if an adverse event is in some way related to the use of the study drug. 
This relationship should be described as follows:


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Unlikely:
The event is clearly due to causes distinct from the use of the study drug, such as a documented pre- 
existing condition, the effect of a concomitant medication, a new condition which, based on the 
pathophysiology of the condition, and the pharmacology of the study drug, would be unlikely related 
to the use of the study drug.
Possible:
The event follows a reasonable temporal sequence from administration of the study drug or the event 
follows a known response pattern to the study drug BUT the event could have been produced by an 
intercurrent medical condition which, based on the pathophysiology of the condition, and the 
pharmacology of the study drug, would be unlikely related to the use of the study drug or the event 
could be the effect of a concomitant medication
Probable:
The event follows a reasonable temporal sequence from administration of the study drug and the 
event follows a known response pattern to the study drug AND the event cannot have been 
reasonably explained by an intercurrent medical condition or the event cannot be the effect of a 
concomitant medication
Definite:
The event follows a reasonable temporal sequence from administration of the study drug, the event 
follows a known response pattern to the study drug and based on the known pharmacology of the 
study drug, the event is clearly related to the effect of the study drug
Unknown:
Based on the evidence available, causality cannot be ascribed


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11
DATA SAFETY MONITORING PLAN
The UCSF Helen Diller Family Comprehensive Cancer Center (UCSF-HDFCCC) Data Safety 
Monitoring Committee (DSMC) is responsible for monitoring data quality and patient safety for all 
UCSF-HDFCCC institutional clinical studies. PCCTC will facilitate this responsibility. A summary of 
DSMC and PCCTC activities for this study includes:
DSMC:

Review of subject data in each cohort

Approval of dose escalation by DSMC Chair (or qualified alternate)

Monthly monitoring (depending on study accrual)

Review of suspected adverse reactions considered “serious”

Minimum of a yearly audit 
PCCTC:
•
Weekly UCSF Site Committee Meetings: PCCTC will generate the necessary report and 
participate in the meeting and document minutes as necessary.
•
UCSF DSMC Reports every 6 weeks: PCCTC will generate the report (in a format agreed upon 
at the onset of the protocol) and provide to Study Chair to submit to DSMC.
•
Bi-Weekly Conference Calls with Participating Sites: PCCTC will coordinate, schedule, provide 
reports for this meeting in a format agreed upon at the onset of the protocol as well as participate 
and take minutes.
•
PCCTC will perform monitoring per the Monitoring Plan (MP) and Data Management Plan 
(DMP) and these reports will be submitted to the Study Chair to submit to the DSMC.
•
PCCTC will monitor grade 3 or 4 adverse events and report to the Study Chair if the incidence of 
adverse events are above the range stated in the IB so that the Study Chair may report this 
information to the DSMC.
•
PCCTC will maintain an electronic regulatory binder for each of the participating sites and supply 
documentation to UCSF as needed.
11.1
Monitoring and Reporting Guidelines
All institutional Phase 1 therapeutic studies are designated with a high risk assessment. The data is 
monitored monthly as subjects are enrolled and includes all visits monitored up through the Dose 
Limiting Toxicity (DLT) period. At the time of dose escalation, a written report generated by PCCTC 
will be submitted to the DSMC Chair outlining the cohort dose, all adverse events and suspected adverse 
reactions considered “serious,” and any Dose Limiting Toxicity as described in the protocol. The report 
will be reviewed by the DSMC Chair or qualified alternate and written authorization to proceed or a 
request for more information will be issued within 2 business days of the request. The report is then 
reviewed at the subsequent DSMC meeting. In the event that the committee does not concur with the 
DSMC Chair’s decision, further study accrual is held while further investigation takes place.
The Principal Investigator at the UCSF Coordinating Center will hold the role of Study Chair. The Study 
Chair is responsible for the overall conduct of the study and for monitoring its safety and progress at all 
participating sites. The Study Chair will conduct continuous review of data and subject safety and discuss 
each subject’s treatment at weekly UCSF Site Committee meetings. PCCTC will generate any necessary 
reports and participate in the meeting as necessary. The discussions are documented in the UCSF Site 
Committee meeting minutes. For each dose level, the discussion will include the number of patients, 
significant toxicities in accordance with the protocol, doses adjustments, and observed responses.


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Dose Level Considerations
The PI/Study Chair, participating sites, investigators, and research coordinators will review enrollment 
for each dose level cohort during the weekly site committee meetings. The dose level for ongoing 
enrollment will be confirmed for each subject scheduled to be enrolled. Dose level assignments for any 
subject scheduled to begin treatment must be confirmed with Principal Investigator.
The DSMC will be responsible for monitoring all data entered in Medidata Rave®. Approval for dose 
escalation must be obtained from DSMC chair.
11.2
Review and Oversight Requirements
11.2.1 Adverse Event Monitoring
All clinically significant adverse events (AEs), whether or not unexpected, and whether or not 
considered to be associated with the use of study drug, will be entered into  Medidata Rave®.
All clinically significant adverse events entered into Medidata Rave® will be reviewed on a 
weekly basis at the UCSF Genitourinary Oncology Site Committee. The Site Committee will 
review and discuss the selected toxicity, the toxicity grade, and the attribution of relationship of 
the adverse event to the administration of the study drug(s). The weekly reports for this meeting 
will be prepared  by PCCTC.  In addition, all suspected adverse reactions considered “serious” 
are entered into Medidata Rave® and will be reviewed and monitored by the Data and Safety 
Monitoring Committee on an ongoing basis and discussed at the DSMC meetings, which take 
place every six (6) weeks. The report for this meeting will be prepared by PCCTC and submitted 
to the DSMC by the Study Chair.
If a death occurs during the treatment phase of the study or within 30 days after the last 
administration of the study drug(s) and is determined to be related either to the investigational 
drug or any research related procedure, the Study Chair at the UCSF Coordinating Center or the 
assigned designee and PCCTC 
must be notified within 24 hours of 
knowledge of the event from the participating site(s) and the Study Chair must then notify the 
DSMC Chair or qualified alternate within 1 business day of this notification. The contact may be 
by phone or e-mail.
11.2.2 Serious Adverse Event Reporting: UCSF Requirements
Serious Adverse Event reporting will be facilitated by PCCTC in accordance with the UCSF 
Institutional Review Board(IRB) Regulations and Food and Drug Administration (FDA) 
guidelines.
UCSF IRB website for guidance in reporting serious adverse events:
http://irb.ucsf.edu/adverse-event
FDA website for guidance in reporting serious adverse events: 
http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm
For clinical trials conducted under an IND, SAE reporting will in accordance with Code of 
Federal Regulations Title 21 volume 5 Part 312 subpart B (21CFR312.32): 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.32


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SAEs will be reported on a MedWatch form. A copy of the MedWatch report must be sent to the 
DSMC 
. The date the SAE was sent to all required reporting agencies will be 
documented in the EDC.  Hard copies of the report will be maintained in the regulatory files.
If the SAE is death and determined to be possibly, probably or definitely related to the 
investigational drug or any research related procedure, the event must be reported to 
PCCTC 
 and the DSMC Chair or his designee within 24 hours 
of becoming aware of the event. This will be done by personal communication via phone or 
in person. The reporting investigator will confirm the verbal communication via e-mail and 
will copy the e-mail to the DSMC Administrator.
If the above action occurs in a multiple-institutional clinical trial coordinated by UCSF, PCCTC 
will insure that all participating sites are notified.
11.2.3 SAE Reporting: Novartis Adverse Event Reporting Requirements
The principal investigator has the obligation to report all serious adverse events to the FDA (if 
applicable), IRB, and Novartis Pharmaceuticals Drug Safety and Epidemiology Department 
(DS&E).
All events reported to the FDA by the investigator are to be filed utilizing the Form FDA 
3500A (MedWatch Form), if applicable.
To ensure patient safety, every SAE, regardless of suspected causality, occurring after the 
patient has provided informed consent and until at least 30 days after the patient has stopped 
study treatment must be reported to Novartis within 24 hours of learning of its occurrence. 
Information about all SAEs is collected and recorded on a Serious Adverse Event Report Form. 
The investigator must assess and record the relationship of each SAE to each specific study 
treatment (if there is more than one study treatment), complete the SAE Report Form in 
English, and send the completed, signed form along with the Novartis provided fax cover 
sheet to the Novartis Oncology Drug Safety and Epidemiology (DS&E) department 
 
within 24 hours.
Any additional information for the SAE including complications, progression of the initial 
SAE, and recurrent episodes must be reported as follow-up to the original episode within 24 
hours of the investigator receiving the follow-up information. An SAE occurring at a different 
time interval or otherwise considered completely unrelated to a previously reported one should 
be reported separately as a new event. 
Any SAEs experienced after the 30 day safety evaluation follow-up period should only be 
reported to Novartis if the investigator suspects a causal relationship to the study treatment. 
Follow-up information is submitted in the same way as the original SAE Report. Each re-
occurrence, complication, or progression of the original event should be reported as a follow-up 
to that event regardless of when it occurs. The follow-up information should describe whether 
the event has resolved or continues, if and how it was treated, whether the blind was broken or 
not, and whether the patient continued or withdrew from study participation. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the Novartis study treatment, an oncology Novartis 
Drug Safety and Epidemiology (DS&E) department associate may urgently require further 
information from the investigator for Health Authority reporting. Novartis may need to issue an 
Investigator Notification (IN), to inform all investigators.


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Pregnancies
To ensure patient safety, each pregnancy occurring while the patient is on study treatment must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. 
Pregnancy should be reported by the investigator to the Novartis Oncology Drug Safety and 
Epidemiology Department (DS&E) 
 Pregnancy follow-up should 
include an assessment of the possible relationship
11.2.4 Review of Adverse Event Rates
Increase in Adverse Event Rates
If an increase in the frequency of Grade 3 or 4 adverse events (above the rate reported in the 
Investigator Brochure or package insert), the Study Chair at the UCSF Coordinating Center is 
responsible for notifying the DSMC at the time the increased rate is identified. The report will be 
generated by PCCTC and indicate if the incidence of adverse events observed in the study is 
above the range stated in the Investigator Brochure or package insert.
If at any time the Study Chair stops enrollment or stops the study due to safety issues, the DSMC 
Chair and DSMC Manager must be notified within 1 business day via e-mail. The DSMC must 
receive a formal letter within 10 business days and the IRB must be notified.
Data and Safety Monitoring Committee Contacts:
DSMC
Chair:
DSMC Monitors
Phone: 
Email: 
Address:
 
UCSF
San Francisco, CA 94158
UCSF Helen Diller Family 
Comprehensive Cancer Center 
San Francisco, CA 94143


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12
DATA MANAGEMENT
This study is a multi-institution, investigator- sponsored trial (IST) coordinated by UCSF and the Prostate 
Cancer Clinical Trials Consortium (PCCTC). The Principal Investigator at UCSF holds the role of Study 
Chair.
The Principal Investigator and/or PCCTC  is required to maintain adequate records of the disposition of 
the drug, including dates, quantity, and use by subjects, as well as written records of the disposition of the 
drug when the study ends.
The Principal Investigator is required to prepare and maintain adequate and accurate case histories that 
record all observations and other data pertinent to the investigation on each individual administered the 
investigational drug or employed as a control in the investigation. Participating sites will prepare and 
maintain adequate and accurate case histories as per their standard institutional guidelines. Case histories 
include the case report forms and supporting data including, for example, signed and dated consent forms 
and medical records including, for example, progress notes of the physician, the individual's hospital 
chart(s), and the nurses' notes. The case history for each individual shall document that informed consent 
was obtained prior to participation in the study.
Study documentation includes all CRFs, data correction forms or queries, source documents, Sponsor- 
Investigator correspondence, monitoring logs/letters, and regulatory documents (e.g., protocol and 
amendments, IRB correspondence and approval, signed patient consent forms).
Source documents include all recordings of observations or notations of clinical activities and all reports 
and records necessary for the evaluation and reconstruction of the clinical research study.
In accordance with FDA regulations, the investigator shall retain records for a period of 2 years following 
the date a marketing application is approved for the drug for the indication for which it is being 
investigated; or, if no application is to be filed or if the application is not approved for such indication, 
until 2 years after the investigation is discontinued and FDA is notified.
Study drugs will be shipped from the drug manufacturer directly to the site for direct distribution of the 
drugs to the study patients.  Each site will be responsible for drug accountability at their site.
Approval of Protocol and Amendments
All protocol amendments must be approved by the participating site’s IRB within 90 days of receipt. 
Failure to do so may result in the suspension of study activities at that site.
Upon approval of the protocol or amendment by a participating site’s IRB, a copy of the approval 
documentation must be submitted (electronic or hardcopy) to PCCTC. PCCTC will inform the Study 
Chair.
Data Submission
Standardized eCRFs and completion guidelines will be created by the PCCTC for the collection of all 
study data. Access and training for Medidata Rave will be made available to participating sites upon local 
regulatory approval. The participating site PI is responsible for ensuring eCRFs are completed accurately 
and in a timely manner.
All participating sites will be granted access to Medidata Rave and will be expected to enter data as 
described in the Medidata Rave Data Guidelines provided by PCCTC.


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13
ETHICAL AND REGULATORY CONSIDERATIONS
13.1
Protocol Review Committee
This study will be reviewed by the UCSF Comprehensive Cancer Center Protocol Review Committee 
(PRC) for scientific merit. After initial review and approval, the study will be reviewed at least once a 
year for scientific progress.  Any changes to the protocol are to be reviewed and approved by the PRC.
Participating sites will review this study as per their standard scientific review and approval process.
13.2
Institutional Review Board (IRB) / Independent Ethics Committee (IEC)
The study will be reviewed by the IRB. After initial review and approval, the study will be reviewed at 
least once a year as per FDA regulations (21 CFR 56.109). Any changes to the protocol and consent form 
are to be reviewed and approved by the IRB.  Participating sites will review this study as per their 
standard IRB/IEC review and approval process.
It is the responsibility of the Principal Investigator to keep the IRB informed of the progress of the study, 
including changes to the protocol or consent form, exceptions or deviations from the protocol, and any 
new developments which may affect subject safety or willingness to participate.
13.3
Investigational New Drug Application (IND)
IND application will be filed and approved with FDA prior to study initiation.
A copy of all FDA correspondence will be maintained by the centralized regulatory staff of the UCSF- 
HDFCCC and PCCTC. It is the responsibility of the Study Chair to forward any correspondence 
concerning the IND and FDA to the centralized regulatory staff and PCCTC.
13.4
Conduct of the trial
The investigators will obtain informed consent and will conduct the trial in accordance with Federal 
regulations, institutional requirements, and the Declaration of Helsinki.
Role and Responsibilities
Sponsor Investigator
The Sponsor Investigator is responsible for performing the following tasks:
Responsibility for the overall conduct of the study at all participating sites and for monitoring 
the progress of the study
Reviewing and ensuring reporting of SAEs
Reviewing data from all participating sites
PCCTC (Prostate Cancer Clinical Trials Consortium)
The PCCTC is responsible for performing the following tasks:
Ensuring that IRB approval has been obtained at each participating site prior to the first patient 
registration at that site, and maintaining copies of IRB approvals and required regulatory 
documents from each site.
Managing subject registration


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Developing and maintaining Clinical Data Management documents and procedures
CRF development, setup of study database, and subsequent design changes
Participating in review of content of the CRF against the protocol requirements
Electronic Data Capture (EDC) system administration (user/site accounts setup, maintenance 
and revocation)
Data review, cleaning, query management and resolution
Establishing procedures for documentation, reporting and submitting of AEs and SAEs to the 
PCCTC and UCSF as outlined in Sections 10 and 11
Reviewing SAEs and facilitating regulatory reporting in coordination with Sponsor- 
Investigator.
Training participating sites on EDC
Collecting and compiling data from each participating site
Data reviewing from all participating sites
Facilitating monitoring by securing selected source documents and research records from 
participating sites for audit, or by auditing at participating sites.
Participating Sites
Participating sites are responsible for performing the following tasks:
Following the protocol as written, the guidelines of GCP, and applicable Standard Operating 
Procedures (SOPs).
Registering all patients with the PCCTC by submitting the eligibility checklist, supporting 
source documentation, and signed informed consent promptly
Providing sufficient experienced clinical and administrative staff and adequate facilities and 
equipment to conduct a collaborative trial according to the protocol
Maintaining regulatory binders on site and providing copies of all required documents to the 
PCCTC
Collecting and submitting data according to the schedule specified by the protocol
Responding to queries in a timely manner


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REFERENCES
1.
Siegel R, Ma J, Zou Z, and Jemal A. Cancer statistics, 2014. CA: A Cancer Journal for Clinicians 
2014; 64(1):9-29.
2.
Aggarwal R, Zhang T, Small E, and Armstrong A. Neuroendocrine prostate cancer: subtypes, 
biology, and clinical outcomes. J Natil Compr Canc Netw 2014; 12:719-726
3.
Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus 
prednisone for advanced prostate cancer. New Engl J Med 2004; 351:1502-1512.
4.
Kelly WK, Halabi S, Carducci M, et al. (2012) Randomized, double-blind, placebo-controlled 
phase 3 trial comparing docetaxel and prednisone with or without bevacizumab in men with 
metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol; 30:1534-1540.
5.
Quinn DI, Tangen CM, Hussain M, et al. (2013) Docetaxel and atrasentan versus docetaxel and 
placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised 
phase 3 trial. Lancet Oncology; 14:893-900.
6.
Scher HI, Jia X, Chi K, et al. (2011) Randomized, open-label phase III trial of docetaxel plus
high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate 
cancer. J Clin Oncol; 29(16):2191-2198.
7.
Fizazi KS, Higano C, Nelson JB, et al. (2013) Phase III, randomized, placebo-controlled study of 
docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate 
cancer. J Clin Oncol; 31:1740-1747.
8.
Tannock IF, Fizazi K, Ivanov S, et al. (2013) Aflibercept versus placebo in combination with 
docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer 
(VENICE): a phase 3, double-blind randomised trial. Lancet Oncol; 14:760-768.
9.
Araujo JC, Trudel GC, Saad F, et al. (2013) Docetaxel and dasatinib or placebo in men with 
metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 
trial. Lancet Oncol; 14:1307-1316.
10. Higano C, Saad F, Somer B, et al. (2009) A phase III trial of GVAX immunotherapy for prostate 
cancer versus docetaxel plus prednisone in asymptomatic, castration-resistant prostate cancer 
(CRPC). J Clin Oncol; 27:14
11. Petrylak DP, Fizazi K, Sternberg CN, et al. (2012) A phase III study to evaluate the efficacy and 
safety of docetaxel and prednisone with or without lenalidomide in patients with castrate-resistant 
prostate cancer: The MAINSAIL trial. Meeting of the European Society of Medical Oncology, 
Vienna, Austria, September 28-October 2, 2012 (abstr LBA24).
12. Cho H, Herzka T, Zheng W, et al. (2014) RapidCaP, a novel GEM model for metastatic prostate 
cancer analysis and therapy, reveals MYC as a driver of Pten-mutant metastasis. Cancer 
Discovery; 4:318-333.
13. Korpal M, Korn JM, Gao X, et al. (2013) An F876L mutation in androgen receptor confers 
phenotypic resistance to MDV3100 (enzalutamide). Cancer Discovery; 3:1030-1043.
14. Horiuchi D, Kusdra L, Huskey NE, et al. (2012) NYC pathway activation in triple-negative breast 
cancer is synthetic lethal with CDK inhibition. J of Experimental Medicine;679-696.
15. Taylor BS, Schultz N, Hieronymous H, et al. (2010) Integrative genomic profiling of human 
prostate cancer. Cancer Cell; 18:11-22.
16. Beltran H, Rickman DS, Park K, et al. Molecular characterization of neuroendocrine prostate 
cancer and identification of new drug targets. Cancer Discovery 2011;1:487-495.
17. Rigas AC, Robson CN, and Curtin NJ. Therapeutic potential of CDK inhibitor NU2058 in 
androgen-independent prostate cancer. Oncogene 2007;26:7611-7619.
18. Liu G, Gandara DR, Lara PN, et al. (2004) A phase II trial of flavopiridol in patients with 
previously untreated metastatic androgen-independent prostate cancer. Clin Cancer Res; 10:924- 
928.


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19. Nanni, C. (2010). 68Ga-citrate PET/CT for evaluating patients with infections of the bone: 
preliminary results. Journal of nuclear medicine : official publication, Society of Nuclear 
Medicine 51, 1932-1936


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APPENDIX 1:  ECOG Performance Status Scale
Out of bed >50% of time; occasionally needs help
2
DESCRIPTION
SCALE
Normal Activity
0
Symptoms of disease, able to carry out activities of daily living
1
In bed >50% of time; needs nursing care
3
Bedridden; may need hospitalization
4


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APPENDIX 2: List of Prohibited Medications
In general, the use of any concomitant medication deemed necessary for the care of the patient is 
permitted in this study, except as specifically prohibited below. Combination administration of 
study drugs could result in drug-drug interactions (DDI) that could potentially lead to reduced 
activity or enhanced toxicity of the concomitant medication and/or ribociclib.
The following lists are not comprehensive and are only meant to be used as a guide. The lists are based 
on the Oncology Clinical Pharmacology Drug-Drug Interaction Database (release date: 29 Oct 2012), 
which was compiled from the Indiana University School of Medicine’s P450 Drug Interaction Table 
(http://medicine.iupui.edu/clinpharm/ddis/main-table/) and supplemented with the FDA Draft 
Guidance for Industry, Drug Interaction Studies – Study Design, Data Analysis, and Implications for 
Dosing and Labeling (February 2012) 
(http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm2923
62. pdf), and the University of Washington’s Drug Interaction Database 
(http://www.druginteractioninfo.org/). For current lists of medications that may cause QT prolongation 
and/or torsades de pointes (TdP), refer to the CredibleMeds® website (https://crediblemeds.org/). 
Please contact the medical monitor with any questions.
Category
Drug Name
Strong CYP3A4/5 inhibitors
Atazanavir/ritonavir, boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir/ritonavir, 
darunavir/ritonavir, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir, 
indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, 
nelfinavir,ombitasvir/paritaprevir/dasabuvir/ritonavir (VIEKIRA PAK), posaconazole, 
ritonavir,  saquinavir/ritonavir, telaprevir, telithromycin, tipranavir/ritonavir, 
troleandomycinvoriconazole
Strong CYP3A4/5 inducers
carbamazepine3, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin3, rifabutin, 
rifampin (rifampicin)3, St. John's wort (hypericum perforatum)2,3
Medications with a known 
risk for QT prolongation4
Amiodarone, anagrelide, arsenic trioxide, astemizole, azithromycin, chloroquine,  
chlorpromazine, cilostazol, ciprofloxacin, cisapride, citalopram, clarithromycin, 
disopyramide, dofetilide, domperidone, donepezil, dronedarone, droperidol, erythromycin, 
escitalopram, flecainide, fluconazole, gatifloxacine, grepafloxacin, halofantrine, haloperidol, 
ibutilide, levofloxacin, levomepromazine, levosulpiride, methadone, moxifloxacin, 
ondansetron, oxaliplatin, papaverine HCl (intra-coronary), pentamidine, pimozide,  
procainamide, propofol, quinidine, roxithromycin, sevoflurane, sotalol,  sulpiride, sultopride, 
terlipressin, terodiline,  thioridazine, vandetanib
CYP3A4/5 substrates with NTI1 Alfentanil, astemizole, cisapride, cyclosporine, diergotamine (dihydroergotamine), 
ergotamine, fentanyl,  pimozide, quinidine,  sirolimus, tacrolimus
Other investigational and 
antineoplastic therapies 
not part of the study
Other investigational therapies must not be used while the patient is on the study. 
Anticancer therapy (chemotherapy, all SERMS (including raloxifene) biologic or radiation 
therapy, and surgery) other than the study treatments must not be given to patients while 
the patient is on the study medication. If such agents are required for a patient then the 
patient must be discontinued from the study.
Herbal 
preparations/ 
medications
Herbal preparations/medications that are strong inhibitors or inducers of CYP3A4/5 or 
those with a known risk of QT prolongation are prohibited throughout the study. These 
herbal medications include, but are not limited to: black cohosh, St. John’s wort, Kava, 
ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw 
palmetto, and ginseng. Patients should stop using these herbal medications 7 days prior to 
first dose of study drug.


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1 NTI = narrow therapeutic index drugs whose exposure-response indicates that increases in their exposure levels by the 
concomitant use of potent inhibitors may lead to serious safety concerns (e.g., Torsades de Pointes). or drugs which have 
<2-fold difference in the minimum toxic concentrations and minimum effective concentrations in the blood.
2 Herbal product
3 P-gp inducer
   4 The list provided is as of January 2018.Check https www crediblemeds.org/healthcare-providers/drug-list for the most   
    updated list. 
  As far as possible, avoid co-administration of QT prolonging drugs or any other drugs with the potential to increase the      
  risk of drug-related QT prolongation (e.g., via a potential DDI that increases the exposure of ribociclib or the exposure of  
  the QT prolonging drug). A definitive list of drugs with a known risk, possible risk, or conditional risk of QT prolongation 
  and/or Torsades de Pointes (TdP) is available online at qtdrugs.org.
Source: Novartis PK Sciences Memorandum: Drug-Drug Interactions (DDI) and Co-medication Considerations for Novartis 
Clinical Trials (January 2018), which is compiled from Indiana University “Clinically Relevant” Flockhart Table™, University of 
Washington Drug Interaction Database, and FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors 
and Inducers.


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APPENDIX 3: List of Medications To be Used With Caution
Category
Drug Name
Moderate CYP3A4/5 inhibitors
Aprepitant, amprenavir, asafoetida resin (Ferula asafoetida) cimetidine, 
crizotinib, diltiazem, faldaprevir,  imatinib,  isavuconazole, netupitant, 
nilotinib, tofisopam, Schisandra sphenanthera (nan wu wei zi), verapamil
Moderate CYP3A4/5 inducers
Bosentan, dabrafenib, efavirenz, etravirine, genistein,lopinavir5, 
modafinil, nafcillin, telotristat
Sensitive CYP3A4/5 substrates1
Alpha-dihydroergocryptine,  aprepitant,  atorvastatin, avanafil, 
bosutinib,brotizolam, budesonide, buspirone,  cobimetinib,   darifenacin, 
dasatininb, ebastine, eletriptan, eplerenone, everolimus, felodipine, 
fluticasone, grazoprevir, ibrutnib, isavuconazole, ivabradine, ivacaftor, , 
levomethadyl (LAAM), lomitapide, lovastatin, lumefantrine, lurasidone, 
maraviroc, midazolam, midostaurin, naloxegol, neratinib, nisoldipine, 
perospirone, quetiapine, ridaforolimus, sildenafil, simeprevir, simvastatin, 
ticagrelor, tilidine,  tolvaptan, triazolam, ulipristal, vardenafil, venetoclax, 
vicriviroc, voclosporin
BSEP inhibitors
Alectinib, atorvastatin,  bromocriptine, candesartan, clobetasol, 
clofaziminie, dabigatran, dipyridamole, glyburide, grazoprevir, 
ledipasvir, mifepristone,pioglitazone, reserpine,rifamycin, simeprevir, 
telmisartan,timcodar, troglitazone, valinomycin, velpatasvir
MATE1/2 substrates3
Acyclovir, cephalexin, cimetidine, fexofenadine, ganciclovir, 
glycopyrronium, metformin, pindolol, plisicainide, ranitidine, 
topotecan, varenicline
OCT1/2 substrates4
Amantadine, 6-beta-hydroxycortisol, carboplatin, cisplatin, cephalexin, 
cephradine, ipratropium, lamivudine, linagliptin, metformin, oxyplatin, 
oxybutynin, phenformin, picoplatin, pilsicainide, pindolol, ranitidine, 
sorafenib,  tropisetron, trospium, umeclidinium, and zidovudine
BCRP substrates
Daunorubicin, dolutegravir, doxorubicin, hematoporphyrin, imatinib, 
methotrexate, mitoxantrone, pitavastatin, rosuvastatin, irinotecan, ethinyl 
estradiol, simvastatin, sulfasalazine, sofosbuvir, tenofovir, topotecan, 
venetoclax


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Medications that carry a possible risk 
for QT prolongation2
Alfuzosin, apomorphine, aripiprazole, artenimol+piperaquine , asenapine, 
atomoxetine,  bedaquiline, bendamustine, bortezomib, bosutinib, 
buprenorphine, cabozantinib, capecitabine, ceritinib, clomipramine, 
crizotinib,clozapine, cyamemazine (cyamepromazine), dabrafenib, dasatinib, 
degarilix, delamanid, desipramine, dexmedetomidine, dolasetron, efavirenz, 
eliglustat, epirubicin, eribulin mesylate, ezogabine(retigabine), famotidine, 
felbamate, fingolimod, flupentixol,  gemifloxacin, granisetron, hydrocodone-
ER, iloperidone, imipramine (melipramine), isradipine, ketanserin, lapatinib, 
lenvatinib, leuprolide, lithium, melperone, midostaurin, mifepristone, 
mirabegron, mirtazapine, moexipril/HCTZ, necitumumab, nicardipine, 
nilotinib, norfloxacin, nortriptyline, nusinersen, ofloxacin, osimertinib,  
oxytocin, paliperidone, palonosetron,  panabinostat, pasireotide, pazopanib, 
perflutren lipid microspheres, perphenazine, pilsicainide, pimavanserin, 
pipamperone, promethazine, prothipendyl,  rilpivirine, risperidone, 
romidepsin, sertindole, sorafenib, sunitinib, tamoxifen, tipiracil/trifluridine, 
tizanidine, tolterodine, toremifene,trimipramine, tropisetron, vardenafil, 
vemurafenib, venlafaxine, vorinostat, ziprasidone
1
Sensitive substrates: Drugs whose plasma AUC values have been shown to increase 5-fold or higher when co- 
administered with a potent inhibitor.
2
The list provided is as of January 2018. Check https www crediblemeds.org/healthcare-providers/drug-list for 
the most updated list. 
3
MATE1 and MATE2 share considerable substrate specificity. 
4
OCT1 and OCT2 share considerable substrate specificity.
5
Lopinavir is prohibited when combined with ritonavir (see Table 14-1)
Source: Novartis PK Sciences Memorandum: Drug-Drug Interactions (DDI) and Co-medication Considerations for 
Novartis Clinical Trials (January 2018), which is compiled from Indiana University “Clinically Relevant” Flockhart 
Table™, University of Washington Drug Interaction Database, and FDA Drug Development and Drug Interactions: 
Table of Substrates, Inhibitors and Inducers.


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APPENDIX  4: Pharmacokinetics (PKs) Collection Instructions (Phase 1b only)
Please see separately attached Appendix 4.


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APPENDIX 5: Plasma/Serum/Peripheral Blood Mononuclear Cell (PBMC) Banking 
(Optional)
Please see separately attached Appendix 5.


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APPENDIX 6: Circulating Tumor Cells (CTCs) and Cell-Free Circulating Tumor DNA 
(ctDNA) Collection and Processing Instructions
Please see separately attached Appendix 6.


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APPENDIX 7: Tumor Biopsy Procedure (Optional)
Please see separately attached Appendix 7.


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APPENDIX 8: ECOG/KPS Conversion Scale

ICF_001.pdf: 
P h as e 1 b C o ns e nt
P a g e 1 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
U NI V E R SI T Y O F C A LI F O R NI A, S A N F R A N CI S C O
C O N S E N T T O P A R TI CI P A T E I N A R E S E A R C H S T U D Y
C C # 1 4 5 5 1 5: A P h ase 1 b St u d y of t he Or al C D K 4/ 6 I n hi bit or Ri b ocicli b i n C o m bi n ati o n 
wit h D ocet a xel Pl us Pre d nis o ne i n Met ast atic C astr ati o n- Resist a nt Pr ost ate C a ncer
I nf or me d C o nse nt F or m
T his is a cli nical trial, a t y pe of researc h st u d y. Y o ur st u d y d oct or Ra h ul A g gar wal, M. D. fr o m 
t he U C S F Hele n Diller Fa mil y C o m pre he nsi ve Ca ncer Ce nter will e x plai n t he cli nical trial t o 
y o u.
Cli nical trials i ncl u de o nl y pe o ple w h o c h o ose t o ta ke part. Please ta ke y o ur ti me t o ma ke y o ur 
decisi o n a b o ut partici pati n g. Y o u ma y disc uss y o ur decisi o n wit h y o ur fa mil y a n d frie n ds a n d 
wit h y o ur healt h care tea m. If y o u ha ve a n y q uesti o ns, y o u ma y as k y o ur st u d y d oct or.
Y o u are bei n g as ke d t o ta ke part i n t his researc h st u d y beca use y o u are a patie nt wit h metastatic 
pr ostate ca ncer w h ose t u m or has gr o w n des pite h or m o nal t hera p y.
W h y is t his st u d y bei n g d o ne ?
T he p ur p ose of t his st u d y is t o lear n w het her ri b ocicli b ( L E E 0 1 1), w he n a d de d t o a treat me nt 
( d oceta xel pl us pre d nis o ne) a p pr o ve d f or y o ur t y pe of pr ostate ca ncer, hel ps t o sta bilize or st o p 
pr o gressi o n of y o ur ca ncer.
We wa nt t o test t he safet y of ri b ocicli b i n c o m bi nati o n wit h d oceta xel pl us pre d nis o ne at 
differe nt d ose le vels. We wa nt t o fi n d o ut w hat effects, g o o d a n d/ or ba d, it has o n y o u a n d y o ur 
t y pe of ca ncer.
Ri b ocicli b is a dr u g desi g ne d t o bl oc k certai n pr otei ns calle d c ycli n- de pe n de nt pr otei n ki nases 
t hat are re q uire d f or cells t o di vi de. T hese pr otei ns ma y als o c o ntr ol t he a bilit y of certai n ca ncers 
t o gr o w.
Ri b ocicli b is a dr u g t hat has n ot bee n a p pr o ve d b y U. S. F o o d a n d Dr u g A d mi nistrati o n ( F D A) or 
a n y ot her healt h a ut h orities f or t he treat me nt of pe o ple wit h y o ur me dical c o n diti o n. Ri b ocicli b is 
c urre ntl y n ot “ o n t he mar ket” (a vaila ble f or y o u t o b u y) i n a n y c o u ntr y. As of t he last u p date, 
ri b ocicli b has bee n a d mi nistere d t o 1 7 9 patie nts as a si n gle a ge nt.
D oceta xel is a t y pe of c he m ot hera p y t hat bl oc ks cells fr o m di vi di n g. D oceta xel, i n c o m bi nati o n 
wit h a l o w d ose of a ster oi d calle d pre d nis o ne, has bee n s h o w n t o be a n effecti ve treat me nt f or 
y o ur t y pe of pr ostate ca ncer a n d has bee n a p pr o ve d b y t he U. S. F o o d a n d Dr u g A d mi nistrati o n.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0
N C T # 0 2 4 9 4 9 2 1


P h as e 1 b C o ns e nt
P a g e 1 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
U NI V E R SI T Y O F C A LI F O R NI A, S A N F R A N CI S C O
C O N S E N T T O P A R TI CI P A T E I N A R E S E A R C H S T U D Y
C C # 1 4 5 5 1 5: A P h ase 1 b St u d y of t he Or al C D K 4/ 6 I n hi bit or Ri b ocicli b i n C o m bi n ati o n 
wit h D ocet a xel Pl us Pre d nis o ne i n Met ast atic C astr ati o n- Resist a nt Pr ost ate C a ncer
I nf or me d C o nse nt F or m
T his is a cli nical trial, a t y pe of researc h st u d y. Y o ur st u d y d oct or Ra h ul A g gar wal, M. D. fr o m 
t he U C S F Hele n Diller Fa mil y C o m pre he nsi ve Ca ncer Ce nter will e x plai n t he cli nical trial t o 
y o u.
Cli nical trials i ncl u de o nl y pe o ple w h o c h o ose t o ta ke part. Please ta ke y o ur ti me t o ma ke y o ur 
decisi o n a b o ut partici pati n g. Y o u ma y disc uss y o ur decisi o n wit h y o ur fa mil y a n d frie n ds a n d 
wit h y o ur healt h care tea m. If y o u ha ve a n y q uesti o ns, y o u ma y as k y o ur st u d y d oct or.
Y o u are bei n g as ke d t o ta ke part i n t his researc h st u d y beca use y o u are a patie nt wit h metastatic 
pr ostate ca ncer w h ose t u m or has gr o w n des pite h or m o nal t hera p y.
W h y is t his st u d y bei n g d o ne ?
T he p ur p ose of t his st u d y is t o lear n w het her ri b ocicli b ( L E E 0 1 1), w he n a d de d t o a treat me nt 
( d oceta xel pl us pre d nis o ne) a p pr o ve d f or y o ur t y pe of pr ostate ca ncer, hel ps t o sta bilize or st o p 
pr o gressi o n of y o ur ca ncer.
We wa nt t o test t he safet y of ri b ocicli b i n c o m bi nati o n wit h d oceta xel pl us pre d nis o ne at 
differe nt d ose le vels. We wa nt t o fi n d o ut w hat effects, g o o d a n d/ or ba d, it has o n y o u a n d y o ur 
t y pe of ca ncer.
Ri b ocicli b is a dr u g desi g ne d t o bl oc k certai n pr otei ns calle d c ycli n- de pe n de nt pr otei n ki nases 
t hat are re q uire d f or cells t o di vi de. T hese pr otei ns ma y als o c o ntr ol t he a bilit y of certai n ca ncers 
t o gr o w.
Ri b ocicli b is a dr u g t hat has n ot bee n a p pr o ve d b y U. S. F o o d a n d Dr u g A d mi nistrati o n ( F D A) or 
a n y ot her healt h a ut h orities f or t he treat me nt of pe o ple wit h y o ur me dical c o n diti o n. Ri b ocicli b is 
c urre ntl y n ot “ o n t he mar ket” (a vaila ble f or y o u t o b u y) i n a n y c o u ntr y. As of t he last u p date, 
ri b ocicli b has bee n a d mi nistere d t o 1 7 9 patie nts as a si n gle a ge nt.
D oceta xel is a t y pe of c he m ot hera p y t hat bl oc ks cells fr o m di vi di n g. D oceta xel, i n c o m bi nati o n 
wit h a l o w d ose of a ster oi d calle d pre d nis o ne, has bee n s h o w n t o be a n effecti ve treat me nt f or 
y o ur t y pe of pr ostate ca ncer a n d has bee n a p pr o ve d b y t he U. S. F o o d a n d Dr u g A d mi nistrati o n.
N C T # 0 2 4 9 4 9 2 1


P h as e 1 b C o ns e nt
P a g e 2 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
T his will be t he first ti me t hat all t hree dr u gs, ri b ocicli b, d oceta xel, a n d pre d nis o ne are use d i n 
c o m bi nati o n t o treat patie nts.
N o vartis P har mace uticals, I nc. w hic h ma n ufact urers ri b ocicli b is s u p pl yi n g t he st u d y dr u g free-
of-c har ge a n d is pr o vi di n g s u p p ort t o t he i n vesti gat or a n d t he i nstit uti o n t o c o n d uct t he st u d y. 
T he Pr ostate Ca ncer F o u n dati o n is als o pr o vi di n g f u n di n g f or t his st u d y.
H o w m a n y pe o ple will t a ke p art i n t his st u d y ?
T here are t w o parts t o t his st u d y; a d ose-fi n di n g part ( p hase I b) a n d a d ose e x pa nsi o n/ p hase II 
part, y o u will o nl y be partici pati n g i n t he d ose-fi n di n g part ( p hase I b). A p pr o xi matel y 9- 1 8 
patie nts will partici pate i n t he d ose-fi n di n g part ( p hase I b) at U C S F.
W h at will h a p pe n if I t a ke p art i n t his rese arc h st u d y ?
Y o u will recei ve o ne of t hree d osa ges of ri b ocicli b, i n c o m bi nati o n wit h a sta n dar d d ose of 
d oceta xel a n d pre d nis o ne. Gr o u ps of t hree t o si x patie nts will recei ve treat me nt at a gi ve n d osa ge 
le vel of ri b ocicli b. If, d uri n g t he first 2 8 da ys of treat me nt, fe w seri o us si de effects are o bser ve d, 
a ne w gr o u p of t hree t o si x patie nts will j oi n t he st u d y. Eac h gr o u p of patie nts will be treate d 
wit h t he sta n dar d d ose of d oceta xel a n d pre d nis o ne, gi ve n t o get her wit h i ncreasi n g d oses of 
ri b ocicli b, u ntil t he hi g hest t olera ble d oses are i de ntifie d.
Y o u will be treate d wit h t he c o m bi nati o n of ri b ocicli b pl us d oceta xel + pre d nis o ne f or u p t o 9 
c ycles. If t here is n o e vi de nce of pr o gressi o n after 9 c ycles, y o u ma y c o nti n ue o n si n gle a ge nt 
mai nte na nce ri b ocicli b u ntil t he ti me of disease pr o gressi o n. T he d ose of ri b ocicli b use d d uri n g 
mai nte na nce will be t he sa me d ose as t hat i m me diatel y prece di n g cessati o n of d oceta xel 
treat me nt.
W hic h d ose of ri b ocicli b y o u recei ve will de pe n d o n t he pr o gress of t he st u d y a n d t he si de 
effects see n wit h ot her patie nts o n t he st u d y. Y o u will n ot be a ble t o c h o ose w hic h d ose of 
ri b ocicli b y o u recei ve.
Y o u will be as ke d if y o u all o w f urt her researc h t o be perf or me d o n left o ver t u m or sa m ples. 
W het her or n ot y o u a gree t o t his o pti o nal researc h will n ot affect y o ur a bilit y t o partici pate i n t he 
mai n p orti o n of t he st u d y. Please refer t o t he e n d of t his c o nse nt f or m f or a n y i nf or mati o n a b o ut 
o pti o nal researc h.
D osi n g a d mi nistr ati o n i nstr ucti o ns:

D oceta xel will be a d mi nistere d t hr o u g h o ne of y o ur vei ns o n t he first da y of eac h 3- wee k
treat me nt c ycle.

Pre d nis o ne will be ta ke n orall y t wice dail y e ver y da y of eac h 3- wee k c ycle.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 3 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Ri b ocicli b will be ta ke n orall y o nce dail y o n da ys 1- 4 a n d 8- 1 5 of eac h 3- wee k c ycle.

Fil grasti m (als o calle d Ne u p o ge n) will be a d mi nistere d u n der t he s ki n o n da ys 5- 7 of
eac h 3- wee k c ycle as well as a d diti o nal d oses as nee de d.

O n m ost da ys, y o u will ta ke st u d y dr u gs at h o me. O n t he da ys y o u c o me t o cli nic, y o u
will wait t o ta ke t he st u d y dr u gs d uri n g t he visit o nce y o u are i nstr ucte d t o d o s o.

Y o u s h o ul d s wall o w ri b ocicli b ca ps ules wit h a lar ge glass of water at t he sa me ti me eac h
m or ni n g.

Y o u s h o ul d s wall o w t he ri b ocicli b ca ps ules w h ole a n d n ot c he w, cr us h, or o pe n t he m.

Y o u s h o ul d ta ke pre d nis o ne ta blets i n t he m or ni n g a n d mi d-after n o o n wit h f o o d.

If y o u v o mit after ta ki n g a d ose, d o n ot re peat t he d ose.

D o n ot miss a n y d oses. If y o u f or get t o ta ke y o ur st u d y dr u gs b ut re me m ber wit hi n si x
h o urs of w he n y o u were s u p p ose d t o ta ke t he m, y o u s h o ul d ta ke t he dr u gs. If it is m ore
t ha n si x h o urs, y o u s h o ul d s ki p t he m.

T he st u d y d oct or will i nstr uct y o u o n h o w ma n y ca ps ules or ta blets of eac h dr u g y o u
s h o ul d ta ke.

A v oi d c o ns u m pti o n of gra pefr uit, Se ville ora n ges, p o mel os, a n d star fr uit or pr o d ucts
c o ntai ni n g t he j uice of eac h (i ncl u di n g ja ms a n d mar mala des) d uri n g t he st u d y a n d f or 7
da ys pri or t o t he first d ose of ri b ocicli b. Re g ular ora n ge j uice is all o we d.
Bef ore y o u be gi n t he m ai n p art of t he st u d y:
Y o u will nee d t o ha ve t he f oll o wi n g e xa ms, tests or pr oce d ures t o fi n d o ut if y o u ca n be i n t he 
mai n part of t he st u d y. Ma n y of t hese e xa ms, tests or pr oce d ures are part of re g ular r o uti ne 
ca ncer care a n d ma y be d o ne e ve n if y o u d o n ot j oi n t he st u d y. If y o u ha ve ha d s o me of t he m 
rece ntl y, t he y ma y n ot nee d t o be re peate d. T his will be u p t o y o ur st u d y d oct or. T he t otal ti me t o 
c o m plete t he scree ni n g tests a n d pr oce d ures is a b o ut 8- 1 2 h o urs. T he f oll o wi n g pr oce d ures will 
be d o ne:

A c o m plete me dic al hist or y a n d y o ur c urre nt me dic al c o n diti o n will be c ollecte d
i ncl u di n g i nf or mati o n a b o ut y o ur c urre nt healt h stat us

P h ysical E xa mi nati o n

Vit al si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht a n d wei g ht

Bl o o d s a m ples: A bl o o d sa m ple will be dra w n b y i nserti n g a nee dle i nt o a vei n i n y o ur
ar m ( ~ 4 ta bles p o o ns of bl o o d):
o
C o m plete bl o o d c o u nt ( C B C) wit h differe ntial a n d platelet c o u nt
o
Bl o o d c he mistr y assess me nt
o
P S A
o
Test oster o ne

T o meas ure y o ur disease, y o u will ha ve o ne or m ore of t he f oll o wi n g tests d o ne (t hese
will be d o ne wit hi n 4 2 da ys of re gistrati o n):

C T a n d/ or M RI sca n of t he c hest, a b d o me n, a n d pel vis :
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 4 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

B o ne sc a n: A b o ne sca n is a test t hat ma kes detaile d i ma ges of y o ur b o nes a n d a n y
t u m ors o n t he m. Bef ore t he b o ne sca n, a s mall a m o u nt of ra di oacti ve s u bsta nce is
i njecte d i nt o y o ur vei n. A b o ut 3 h o urs later, y o u will lie o n a ta ble u n der a mac hi ne,
w hic h will ma ke a n i ma ge of y o ur b o nes. T he test itself will ta ke a b o ut 1 h o ur, b ut t he
w h ole pr ocess ta kes u p t o 4 h o urs.

Electr oc ar di o gr a m ( E C G): rec or ds t he electrical acti vit y of y o ur heart. Wires or “lea ds”
will be attac he d t o y o ur c hest wit h a n a d hesi ve a n d y o u will be as ke d t o lie still w hile t he
mac hi ne pri nts o ut a n electrical “rec or d” of y o ur heart acti vit y. T he pr oce d ure is d o ne i n
t he Car di ol o g y De part me nt a n d ta kes a b o ut 1 5- 3 0 mi n utes.

Y o u will be as ke d a b o ut a n y me dici nes y o u are ta ki n g i ncl u di n g o ver-t he-c o u nter
me dici nes, vita mi ns, or her bal treat me nts.

Perf or m a nce st at us t o assess h o w y o ur disease is affecti n g y o ur dail y acti vities.

Eit her a M U G A ( m ulti ple- gate d ac q uisiti o n) sca n or a n E C H O (ec h ocar di o gra m), n o n- 
i n vasi ve tests w hic h ta ke m o vi n g pict ures of y o ur heart will als o be d o ne. T hese will be
d o ne wit hi n 4 2 of re gistrati o n.
o
M U G A sc a n : A M U G A sca n is a test t hat ma kes a m oti o n pict ure t hat s h o ws h o w
well y o ur heart p u m ps bl o o d. T he sca n is perf or me d b y ta ki n g a s mall sa m ple of
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0
o
A C T sc a n is a ra di ol o gical test t hat uses s pecial x-ra y e q ui p me nt t o ma ke detaile d
pict ures of b o d y tiss ues a n d or ga ns. F or t he C T sca n, y o u ma y be gi ve n a  “c o ntrast
material" (a s pecial d ye t hat ma kes it easier f or d oct ors t o see differe nt  tiss ues i n y o ur
b o d y). T he c o ntrast material ma y be gi ve n orall y or t hr o u g h o ne of  y o ur vei ns. Oral
c o ntrast material is gi ve n t o y o u t o dri n k a n d is use d t o hel p  o utli ne t he st o mac h a n d
i ntesti nes. I ntra ve n o us (I V) c o ntrast material is gi ve n t o y o u b y i njecti n g t he c o ntrast
material i nt o a li ne, w hic h is attac he d t o a nee dle i n  y o ur ar m a n d is use d t o get clearer
pict ures of y o ur b o d y ca vit y. After y o u ha ve  bee n gi ve n t he c o ntrast material (eit her b y
m o ut h, b y vei n), y o u will lie flat o n a  ta ble t hat will m o ve y o u i nt o t he C T sca n
mac hi ne. Y o u will be as ke d t o lie still  a n d ma y be as ke d t o h ol d y o ur breat h f or a fe w
sec o n ds. Eac h C T sca n will ta ke a b o ut 1 5 mi n utes t o a half h o ur.
If a C T sca n ca n n ot be perf or me d, a n M RI sc a n will be perf or me d. A n M RI sca n  ta kes
a n i ma ge of y o ur b o d y t o o bser ve t he l ocati o n a n d size of y o ur t u m or. F or  t he M RI
sca n, y o u ma y be gi ve n a "c o ntrast material" (a s pecial d ye t hat ma kes it easier f or
d oct ors t o  see differe nt tiss ues i n y o ur b o d y). Ga d oli ni u m is c o ntrast material t hat
ca uses s o me t u m ors t o a p pear m uc h bri g hter t ha n n or mal tiss ue o n  M RI sca ns t hese
t u m ors ma y n ot be visi ble wit h o ut ga d oli ni u m). T he c o ntrast  material ma y be gi ve n t o
y o u i n y o ur ar m t hr o u g h a cat heter (a ti n y t u be) i nserte d  i nt o a vei n. Y o u will t he n lie
d o w n o n a narr o w be d, w hic h will be place d i n a  t u n nel t hat is 6 feet l o n g b y 2 2 i nc hes
wi de a n d o pe n at eac h e n d. Y o u will lie t here q uietl y f or a b o ut o ne h o ur, d uri n g w hic h
ti me y o u will hear a l o u d mac hi ne- li ke n oise. T he M RI sca n is d o ne i n t he Ra di ol o g y
De part me nt a n d ta kes  a p pr o xi matel y a n h o ur a n d a half t o c o m plete.


P h as e 1 b C o ns e nt
P a g e 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
y o ur o w n bl o o d t hat is t he n “la bele d” wit h a ra di oacti ve s u bsta nce. T he la bele d 
bl o o d sa m ple is t he n re-i njecte d i nt o a vei n i n y o ur ar m a n d all o we d t o circ ulate 
i n y o ur b o d y. O nce t he la bele d bl o o d has circ ulate d ar o u n d y o ur b o d y, a series of 
i ma ges (si milar t o a m o vie) are ta ke n of y o ur heart. Y o u will be as ke d t o lie flat 
o n a ta ble a n d re mai n still f or a b o ut 1 0- 2 0 mi n utes w hile t he pict ures of y o ur 
heart are bei n g ta ke n. T his test is d o ne i n t he N uclear Me dici ne de part me nt a n d 
ta kes a b o ut 9 0 mi n utes.
o
E C H O : T his e xa mi nati o n uses s o u n d wa ves t o ma ke pict ures of y o ur heart,
w hic h hel ps deter mi ne h o w well y o ur heart s q ueezes bl o o d. Y o u will be as ke d t o
lie o n y o ur left si de w hile a tec h nicia n places a pr o be wit h gel o n y o ur c hest t o
create i ma ges of y o ur heart t o deter mi ne t he f u ncti o n a n d size. T he pr oce d ure is
d o ne i n t he Car di ol o g y De part me nt a n d will ta ke a p pr o xi matel y 4 5- 6 0 mi n utes.
D uri n g t he m ai n p art of t he st u d y:
If t he e xa ms, tests, a n d pr oce d ures s h o w t hat meet t he criteria t o be i n t he researc h st u d y a n d y o u 
c h o ose t o ta ke part, y o u will t he n be e nr olle d i n t he researc h st u d y. Eac h c ycle of treat me nt will 
last 2 1 da ys.
C ycle 1, D a y 1 (t his visit will t a ke a b o ut 4 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Start ta ki n g oral pre d nis o ne t wice dail y

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns

First oral d ose of ri b ocicli b

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
P har mac o ki netics – T hese are bl o o d tests t hat will hel p deter mi ne t he le vels of
st u d y dr u g i n y o ur bl o o d at differe nt ti me p oi nts.
C ycle 1, D a y 2 (t his visit will t a ke a b o ut 3 0 mi n utes) 

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Re vie w of si de effects
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 6 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Perf or ma nce stat us

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
P har mac o ki netics – T hese are bl o o d tests t hat will hel p deter mi ne t he le vels of
st u d y dr u g i n y o ur bl o o d at differe nt ti me p oi nts.
C ycle 1, D a ys 5- 7 (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)

Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will
be a d mi nistere d eit her at h o me or i n t he cli nic.
C ycle 1, D a y 8 (t his visit will t a ke a b o ut 1 h o ur)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 1, D a y 1 5 (t his visit will t a ke a b o ut 1 h o ur)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Electr ocar di o gra m ( E C G)

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
Bl o o d c o u nts

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 2, D a y 1 (t his visit will t a ke a b o ut 1 – 1 1/ 2 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Electr ocar di o gra m ( E C G)

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 7 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 2, D a ys 5- 7 (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)
Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will be 
a d mi nistere d eit her at h o me or i n t he cli nic.
D a y 1 of E ver y C ycle T here after (t his visit will t a ke a b o ut 4 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Re vie w of si de effects

Electr ocar di o gra m ( E C G)

Perf or ma nce stat us

C o nc urre nt me dicati o ns
D a ys 5- 7 of E ver y C ycle T here after (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)

Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will
be a d mi nistere d eit her at h o me or i n t he cli nic.
St arti n g C ycle 4 a n d E ver y 3 Tre at me nt C ycles (t his visit will t a ke a b o ut 5 h o urs)
T he f oll o wi n g will be d o ne as part of y o ur r o uti ne care:

C T or M RI of t he c hest/a b d o me n/ pel vis

B o ne sca n
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 8 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
E n d of Tre at me nt Visit (t his visit will t a ke bet wee n 1 h o ur a n d 5 h o urs)
D uri n g t his visit, y o u will ha ve t he f oll o wi n g e xa ms, tests, or pr oce d ures at t he ti me, as 
s pecifie d. T he visit will be d o ne wit hi n 3 0 da ys of t he last treat me nt.
•
P h ysical E xa mi nati o n
•
Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht
•
Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns

C T or M RI of t he c hest/a b d o me n/ pel vis (if n ot alrea d y c o m plete d wit hi n past 2 8 da ys)

B o ne sca n (if n ot alrea d y c o m plete d wit hi n past 2 8 da ys)
Y o u will be c o nt acte d 3 0 d a ys after t he l ast d ose of st u d y tre at me nt . Y o u will be as ke d h o w 
y o u are feeli n g a n d w hat me dicati o ns y o u ha ve bee n ta ki n g.
If y o u wit h dr a w fr o m t he st u d y, a n d y o ur disease has n ot pr o gresse d, y o u ma y be c o ntacte d via 
a p h o ne call, a n d as ke d t o ha ve a C T/ M RI sca n d o ne e ver y t w o m o nt hs t o meas ure y o ur disease 
si nce st o p pi n g st u d y treat me nt. T his will be d o ne f or researc h p ur p oses if t his sca n is d o ne at a 
ti me p oi nt ot her t ha n y o ur r o uti ne resta gi n g ti me p oi nt.
Wit h dr a w al of y o ur c o nse nt t o p artici p ate i n t his st u d y
Y o u ma y deci de t hat y o u n ot o nl y wa nt t o st o p st u d y treat me nt b ut als o d o n ot wa nt t o c o me t o 
a n y f urt her visits, a n d d o n ot wa nt t o ha ve a n y f urt her assess me nts or c o ntact b y t he st u d y staff.
T his is c o nsi dere d as wit h dra wal of y o ur c o nse nt fr o m partici pati o n i n t his st u d y. It is i m p orta nt 
t hat y o u i nf or m y o ur St u d y D oct or.
U C S F will c o nti n ue t o retai n a n d use a n y researc h-relate d res ults t hat ha ve alrea d y bee n 
c ollecte d f or t he st u d y e val uati o n. N o f urt her st u d y-relate d acti vities will ta ke place.
Y o u ca n disc uss f urt her re g ular me dical care wit h y o ur St u d y D oct or. T he c h oice t o wit h dra w 
fr o m researc h partici pati o n will n ot affect y o ur me dical care.
St u d y l oc ati o n: All st u d y pr oce d ures will be d o ne at U C S F Hele n Diller Fa mil y C o m pre he nsi ve 
Ca ncer Ce nter.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 9 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
W h at Will I Be As ke d t o D o W hile P artici p ati n g I n T he St u d y ?
I n or der f or t his st u d y t o pr o vi de g o o d i nf or mati o n a b o ut h o w t he dr u gs w or k, y o u will be as ke d 
t o d o t he f oll o wi n g:

C o m pl y wit h y o ur st u d y d oct or’s i nstr ucti o ns. Please n ote: It is ver y i m p orta nt t hat y o u
ta ke t he me dici ne gi ve n t o y o u j ust as t he d oct or tells y o u t o. D o n ot miss a n y d oses a n d
d o n ot tr y t o d o u ble t he d ose if y o u miss a d ose.

N otif y y o ur st u d y d oct or i m me diatel y of a n y i nj ur y or u n us ual s y m pt o ms d uri n g y o ur
partici pati o n i n t his st u d y.

Re vie w all t he healt h f o o d s u p ple me nts, o ver-t he-c o u nter a n d prescri pti o n me dicati o ns
wit h y o ur st u d y d oct or bef ore ta ki n g t he m.

Wit h t he e xce pti o n of e mer ge ncies, y o u s h o ul d n ot ta ke ot her dr u gs w hile y o u are
partici pati n g i n t he st u d y wit h o ut ha vi n g c o ns ulte d y o ur st u d y d oct or. I n case of a n
e mer ge nc y treat me nt, y o ur st u d y d oct or s h o ul d be i nf or me d i m me diatel y.

Bri n g all of y o ur e xtra st u d y dr u g me dicati o n a n d e m pt y pill b ottles bac k t o t he st u d y
d oct or.

D o n ot eat or dri n k gra pefr uit, Se ville (s o ur/ bl o o d) ora n ges or pr o d ucts c o ntai ni n g t he
j uice of eac h d uri n g t he st u d y, as t hese fr uits a n d t heir j uice ca n i nterfere wit h t he bl o o d
le vels of t he dr u gs. Re g ular ora n ge j uice is o ka y.

O n t he da ys t hat y o u c o me t o cli nic visits, y o u will ta ke t he st u d y dr u g t here. After war d,
y o u will be pr o vi de d wit h e n o u g h st u d y me dicati o n u ntil y o ur ne xt pla n ne d cli nic visit.

Y o u will be as ke d t o rec or d t he date a n d ti me y o u t o o k t he st u d y me dicati o n a n d a n y si de
effects y o u ma y e x perie nce i n a diar y. T his diar y m ust be ret ur ne d t o y o ur st u d y d oct or at
y o ur ne xt visit.

D uri n g t he w h ole d urati o n of treat me nt o n t his st u d y, y o u are n ot all o we d t o partici pate i n
a n ot her cli nical st u d y t hat ma y i nterfere wit h t his st u d y. If y o u are i ntereste d i n
partici pati n g i n a n ot her st u d y, y o u m ust s pea k t o y o ur st u d y d oct or a b o ut it.
H o w l o n g will I be i n t he st u d y ?
Y o u will c o nti n ue st u d y treat me nt u ntil y o u e x perie nce disease pr o gressi o n, disc o nti n ue 
treat me nt d ue t o i nt olera ble t o xicit y, i n vesti gat or decisi o n, or wit h dra w c o nse nt, w hic he ver 
occ urs first. Y o u will be treate d wit h t he c o m bi nati o n of ri b ocicli b pl us d oceta xel + pre d nis o ne 
f or u p t o 9 c ycles. If t here is n o e vi de nce of disease pr o gressi o n after 9 c ycles of pr ot oc ol 
t hera p y, patie nts ma y c o nti n ue o n si n gle a ge nt mai nte na nce ri b ocicli b u ntil t he ti me of disease 
pr o gressi o n.
Y o ur d oct or ca n als o deci de t o wit h dra w y o u fr o m t he st u d y if he/s he feels t hat t his is best f or 
y o u.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 0 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
C a n I st o p bei n g i n t he st u d y ?
Yes. Y o u ca n deci de t o st o p at a n y ti me. Tell t he st u d y d oct or if y o u are t hi n ki n g a b o ut st o p pi n g 
or deci de t o st o p. S he will tell y o u h o w t o st o p y o ur partici pati o n safel y.
It is i m p orta nt t o tell t he st u d y d oct or if y o u are t hi n ki n g a b o ut st o p pi n g s o a n y ris ks ca n be 
e val uate d b y y o ur d oct or. A n ot her reas o n t o tell y o ur d oct or t hat y o u are t hi n ki n g a b o ut st o p pi n g 
is t o disc uss w hat f oll o w- u p care a n d testi n g c o ul d be m ost hel pf ul f or y o u.
T he st u d y d oct or ma y st o p y o u fr o m ta ki n g part i n t his st u d y at a n y ti me if s he belie ves it is i n 
y o ur best i nterest, if y o u d o n ot f oll o w t he st u d y r ules, or if t he st u d y is st o p pe d.
W h at si de effects or ris ks c a n I e x pect fr o m bei n g i n t he st u d y ?
Ris ks are p ossi ble si de effects of st u d y me dici ne, or u n der g oi n g tests, s uc h as i ma gi n g sca ns a n d 
bl o o d or t u m or sa m ple c ollecti o n.
T he p ote ntial si de effects descri be d bel o w f or ri b ocicli b are base d o n tests i n a ni mals a n d 
e x perie nce i n ca ncer s u bjects. It is p ossi ble t hat y o u ma y e x perie nce si de effects t hat are 
u ne x pecte d a n d u nf oresee n. E ver y o ne ta ki n g part i n t he st u d y will be watc he d caref ull y f or a n y 
si de effects. Pre ve nti n g si de effects, w he n p ossi ble, is a n i m p orta nt part of all ca ncer care.
T he p ote ntial si de effects descri be d bel o w f or ri b ocicli b a n d B Y L 7 1 9 are base d o n tests i n 
a ni mals a n d e x perie nce i n ca ncer patie nts. T he p ote ntial si de effects descri be d bel o w f or 
letr oz ole are base d o n e xte nsi ve e x perie nce i n ca ncer patie nts. It is p ossi ble t hat y o u ma y 
e x perie nce si de effects t hat are t otall y u ne x pecte d a n d u nf oresee n. E ver y o ne ta ki n g part i n t he 
st u d y will be watc he d caref ull y f or a n y si de effects, a n d tr yi n g t o pre ve nt t he m, w he n p ossi ble, is 
a n i m p orta nt part of all ca ncer care.
Ris ks rel ate d t o ri b ocicli b
Ri b ocicli b is a n i n vesti gati o nal dr u g a n d n ot all of t he si de effects are k n o w n. Seri o us si de 
effects, i ncl u di n g deat h, are a p ossi bilit y. T he l o n g-ter m effects of ri b ocicli b are als o u n k n o w n. 
Ris ks are p ossi ble si de effects of st u d y me dici ne gi ve n al o ne or i n c o m bi nati o n wit h ot her 
me dicati o n(s), a n d t h ose of ta ki n g bl o o d. Base d o n t he data fr o m o n g oi n g st u dies i n ca ncer 
patie nts, t he f oll o wi n g are t he p ossi ble ris ks wit h ta ki n g ri b ocicli b.
Ver y c o m m o n si de effects (m ay affect m ore t h a n 1 0 % of pe o ple )

L o w w hite bl o o d cell c o u nt w hic h i ncreases t he ris k of i nfecti o ns ( ne utr o pe nia or
le u k o pe nia)

I nfecti o ns (i ncl u di n g uri nar y tract i nfecti o ns, res pirat or y i nfecti o ns, gastr oe nteritis a n d
se vere, p ote ntiall y life-t hreate ni n g i nfecti o ns [se psis; t his is u nc o m m o n])

L o w re d bl o o d cell c o u nt w hic h ca n lea d t o tire d ness a n d wea k ness (a ne mia)
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 1 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Na usea

Diarr hea

V o miti n g

C o nsti pati o n

M o ut h s ores, or pai n, i nfla m mati o n a n d/ or i nfecti o n of t he m o ut h

A b d o mi nal pai n

Tire d ness or ge neralize d wea k ness (fati g ue or ast he nia)

S welli n g of t he ar ms or le gs ( peri p heral oe de ma)

Fe ver ( p yre xia)

I ncrease i n t he bl o o d le vels of li ver para meters as i n dicate d b y li ver tests (s uc h as
tra nsa mi nases a n d/ or bilir u bi n)

Decrease d a p petite

Bac k pai n

Hea dac he

Dizzi ness

S h ort ness of breat h ( d ys p nea)

C o u g h

Hair t hi n ni n g or l oss (al o pecia)

S ki n ras h

Itc hi n g of t he s ki n ( pr urit us)
C o m m o n si de effects (m ay affect u p t o 1 0 % of pe o ple )

L o w platelet c o u nt w hic h ca n lea d t o eas y br uisi n g a n d blee di n g (t hr o m b oc yt o pe nia)

L o w w hite bl o o d cell c o u nt wit h fe ver (fe brile ne utr o pe nia)

L o w l y m p h oc yte c o u nt i n t he bl o o d t hat ca n pre dis p ose t o i nfecti o ns (l y m p h o pe nia)

Fai nti n g e pis o des/tra nsie nt l oss of c o nsci o us ness a n d p ost ural p ost ure (s y nc o pe)

E xcessi ve teari n g of t he e ye (i ncrease d lacri mati o n)

Dr y e ye

Taste alterati o n ( d ys ge usia)

Dr y m o ut h

S ore t hr oat ( or o p har y n geal pai n)

I n di gesti o n heart b ur n ( d ys pe psia)

Li ver t o xicit y ( he pat ot o xicit y: i nj ur y of t he li ver d ue t o li ver cell da ma ge, i ncl u di n g li ver
fail ure [t he latter is u nc o m m o n])

I ncrease i n creati ni ne (a waste pr o d uct i n t he bl o o d) a n d a decrease i n t he ki d ne y’s a bilit y
t o ha n dle t he b o d y’s waste ( bl o o d creati ni ne i ncrease d)

C ha n ges i n t he electrical acti vit y of t he heart calle d Q Tc pr ol o n gati o n. T his is a n
a b n or malit y of t he heart r h yt h m a n d ma y ca use dizzi ness, pal pitati o ns, fai nti n g, a n d i n
se vere cases l oss of c o nsci o us ness a n d e ve n deat h

Decrease d bl o o d calci u m le vels ( h y p ocalcae mia)

Decrease d bl o o d p otassi u m le vels ( h y p o kale mia)
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 2 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Decrease d bl o o d p h os p h or us le vels ( h y p o p h os p hate mia)

Re d ness of t he s ki n or re d de ni n g of t he s ki n (er yt he ma)

Dr y s ki n

L oss of s ki n c ol orati o n/ w hite ni n g, us uall y i n patc hes ( vitili g o)

Se nsati o n of l osi n g bala nce ( verti g o)
Rare b ut I m p orta nt ( m ay affect less t h a n 5 % of pe o ple ):

P ote ntial acc u m ulati o n of ri b ocicli b i n t he t h yr oi d gla n d. I n rats, ri b ocicli b was f o u n d t o
acc u m ulate i n t he t h yr oi d gla n d, b ut t here was n o e vi de nce of da ma ge t o t he t h yr oi d
gla n d. T here ha ve bee n n o re p orts of a b n or mal t h yr oi d f u ncti o n i n a n y patie nt s o far.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d M E K 1 6 2 die d fr o m blee di n g i n t he
brai n, w hic h was c o nsi dere d relate d t o ri b ocicli b a n d M E K 1 6 2 b y t he treati n g p h ysicia n.

O ne patie nt partici pati n g i n a trial was dia g n ose d wit h ac ute l y m p h o blastic le u ke mia
( A L L), w hic h t he treati n g p h ysicia n c o nsi dere d p ossi bl y relate d t o ri b ocicli b.

O ne patie nt partici pati n g i n a trial was dia g n ose d wit h ac ute res pirat or y fail ure, w hic h
was c o nsi dere d p ossi bl y relate d t o ri b ocicli b

F o ur partici pa nt deat hs occ urre d o n a breast ca ncer st u d y, w hic h were c o nsi dere d t o be
relate d t o ri b ocicli b. T w o deat hs were d ue t o ac ute res pirat or y fail ure, a n d t he ot her 
ca uses of deat h were p ne u m o nia a n d s u d de n deat h.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole was dia g n ose d wit h
m yel o d ys plastic s y n dr o me, w hic h was c o nsi dere d p ossi bl y relate d t o ri b ocicli b. 
M yel o d ys plastic s y n dr o me ha p pe ns w he n t he b o ne marr o w, t he material i nsi de y o ur 
b o nes w here y o ur bl o o d cells are ma de, n o l o n ger w or ks n or mall y, w hic h ca n lea d t o 
feeli n g tire d, s h ort of breat h or ha vi n g s mall re d s p ots u n der y o ur s ki n ca use d b y blee di n g 
or i nfecti o ns.  

O n patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole e x perie nce d decrease d
s o di u m le vels. Y o u ma y feel tire d, ha ve a hea dac he, feel na usea or v o mit, or ha ve
cra m ps.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole was dia g n ose d wit h heart
fail ure. Y o u mi g ht feel s h ort of breat h, wea k ness, s welli n g i n y o ur le gs, a n kles or feet, or
a n irre g ular or ra pi d heart beat.
Ris ks a n d si de effects relate d t o d ocet a xel a n d pre d nis o ne i ncl u de t h ose liste d bel o w: 
Li kel y

Ras h

Hair l oss

Fl ui d rete nti o n/s welli n g

Fati g ue

U pset st o mac h

S ore ness a n d/ or wea k ness of m uscles a n d/ or j oi nts
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 3 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

I ncrease d bl o o d s u gar le vels, w hic h ma y ca use i ncrease d t hirst, uri nati o n, a n d fati g ue

L o were d w hite bl o o d cell c o u nt t hat ma y lea d t o i ncrease d ris k of i nfecti o n

L o were d platelet c o u nt t hat ma y lea d t o i ncrease d br uisi n g or blee di n g

L o were d re d bl o o d cell c o u nt t hat ma y ca use tire d ness or s h ort ness of breat h (if t he c o u nt
gets t o o l o w y o u ma y nee d a tra nsf usi o n)
Less Li kel y

Diarr hea

Na usea a n d v o miti n g

M o ut h a n d t hr oat s ores

L oss of a p petite

L oss of refle xes

Dar ke ni n g or li g hte ni n g of fi n ger nail be ds

Peeli n g s ki n o n ha n ds a n d feet

I ns o m nia

N u m b ness a n d/ or ti n gli n g of t he fi n gers a n d t oes
Rare, b ut seri o us

St o mac h ulcers a n d/ or blee di n g

Se vere aller gic reacti o n (life-t hreate ni n g breat hi n g pr o ble ms)

A b n or mal f u ncti o n of t he a dre nal gla n d w hic h ca n ca use wea k ness a n d fati g ue, l o w bl o o d
press ure, na usea, v o miti n g, diarr hea, irrita bilit y a n d/ or restless ness, l oss of b o ne de nsit y

L o w bl o o d press ure

A b n or mal c ha n ges i n pers o nalit y
I n a d diti o n, y o u s h o ul d ne ver st o p t he pre d nis o ne s u d de nl y. If y o u nee d t o st o p t he pre d nis o ne, 
y o ur d oct or will a d vise y o u o n h o w t o sl o wl y st o p t he dr u g (calle d a “ta per”). If y o u were t o st o p 
ta ki n g pre d nis o ne s u d de nl y, y o u c o ul d bec o me ver y wea k a n d tire d, de vel o p ver y l o w bl o o d 
press ure, ver y l o w bl o o d s u gar, a n d a b n or malities of t he mi nerals i n y o ur bl o o dstrea m. W hile 
us uall y n ot se vere, if n ot treate d, t hese a b n or malities are p ote ntiall y fatal. If y o u ha ve a seri o us 
ill ness, i nfecti o n, or tra u ma, it will be necessar y t o i ncrease y o ur d ose of pre d nis o ne. A n yti me 
y o u see a d oct or f or a n y reas o n, y o u s h o ul d tell hi m/ her t hat y o u are ta ki n g pre d nis o ne.
We d o n ot k n o w t he si de effects of ri b ocicli b, d oceta xel, a n d pre d nis o ne w he n gi ve n al o ne or i n 
c o m bi nati o n wit h ot her dr u gs. A c o m bi nati o n of dr u gs mi g ht res ult i n seri o us or e ve n life-
t hreate ni n g si de effects. S o me o ver-t he-c o u nter a n d prescri pti o n me dicati o ns ca n re d uce t he 
effecti ve ness or i ncrease t he si de effects of t he st u d y treat me nts. Li ke wise, t he st u d y treat me nts 
ca n i ncrease t he si de effects or lesse n t he effecti ve ness of s o me me dicati o ns. T his mi g ht res ult i n 
seri o us or e ve n life-t hreate ni n g si de effects. Y o u s h o ul d al wa ys disc uss t he use of a n y dr u gs 
( o ver-t he-c o u nter dr u gs, prescri pti o n, or ille gal dr u gs or healt h f o o d s u p ple me nts) wit h y o ur 
d oct or w hile y o u are partici pati n g i n t his st u d y. T he st u d y pr ot oc ol descri bes w hic h me dici nes 
are pr o hi bite d d uri n g t he st u d y, a n d w hic h o nes ca n be ta ke n wit h ca uti o n.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 4 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
T here c o ul d be a d diti o nal u ne x pecte d si de effects w he n ri b ocicli b is ta ke n i n c o m bi nati o n wit h 
d oceta xel a n d pre d nis o ne.
Ris ks rel ate d t o Ne u p o ge n ( G- C S F):
G- C S F ca uses b o ne pai n i n ma n y pe o ple. T his pai n ma y occ ur i m me diatel y or se veral da ys after
recei vi n g G- C S F. T he pai n ma y feel li ke a n ac hi n g se nsati o n i n t he b o nes of t he bac k, hi ps,
pel vis, or breast b o ne. Pai n relie vers, s uc h as aceta mi n o p he n ( T yle n ol ®) or i b u pr ofe n ( A d vil ®,
N u pri n ®) ma y be use d t o lesse n t his disc o mf ort.
Occasi o nall y, G- C S F ma y ca use fl u-li ke s y m pt o ms. If y o u alrea d y ha ve i nfla m mati o n of certai n 
bl o o d vessels, art hritis, ecze ma or ps oriasis, G- C S F ma y ca use t hese c o n diti o ns t o get w orse. 
Ot her occasi o nal si de effects i ncl u de hea dac hes, m uscle ac hes, tire d ness, na usea a n d v o miti n g, 
a n d tr o u ble slee pi n g. T hese s y m pt o ms us uall y g o a wa y wit hi n 2 or 3 da ys after st o p pi n g G- C S F.
T he f oll o wi n g si de effects are rare a n d are n ot ge nerall y seri o us pr o ble ms:

B ur ni n g, s welli n g, a n d re d ness at t he i njecti o n site

Aller gic reacti o ns ( hi ves/s ki n ras h, itc hi n g, w heezi n g, fe ver, ra pi d heart rate, s h ort ness of
breat h, dizzi ness)

L o weri n g of bl o o d press ure

C ha n ges i n bl o o d c he mistr y le vels

E nlar ge me nt of t he s plee n (see n i n s o me patie nts treate d wit h G- C S F f or a n e xte n de d
peri o d of ti me)
Rare b ut seri o us:

Se vere reacti o ns t o G- C S F i n patie nts wit h sic kle cell a ne mia a n d relate d sic kle cell
diseases.

Pai n a n d blee di n g fr o m t he s plee n, w hic h ma y re q uire s ur ger y. If y o u feel pai n i n y o ur
u p per left si de j ust bel o w t he ri b ca ge, c o ntact y o ur d oct or i m me diatel y.
Ot her ris ks rel ate d t o t his st u d y i ncl u de:
Bl o o d dr a wi n g ( ve ni p u nct ure) ris ks: Dra wi n g bl o o d ma y ca use te m p orar y disc o mf ort fr o m t he 
nee dle stic k, br uisi n g, a n d i nfecti o n. I n rare i nsta nces w here a n urse, a d oct or, or a la b orat or y 
tec h nicia n s ustai ns a n e x p os ure t o y o ur bl o o d, tiss ue or b o d y fl ui ds b y nee dle stic k, c ut or s plas h 
t o m uc osa or da ma ge d s ki n, it ma y be necessar y t o test y o ur bl o o d, tiss ue, or b o d y fl ui d sa m ple 
f or certai n viral i nfecti o ns i ncl u di n g He patitis B a n d C a n d HI V o n t he sa m ple alrea d y a vaila ble. 
T his is t o e na ble t hat pers o n t o recei ve a p pr o priate c o u nseli n g, m o nit ori n g, a n d treat me nt if 
necessar y. I n t his i nsta nce, t he St u d y D oct or will offer y o u t he i nf or mati o n rele va nt t o y o ur 
healt h a n d a d vise y o u o n t he ne xt ste ps. C o nfi de ntialit y of y o ur data will be res pecte d at all 
ti mes.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
C T sc a n ris ks: C T sca ns i n v ol ve t he ris ks of ra diati o n. I n a d diti o n, if c o ntrast material (i o di ne 
d ye) is use d, t here is a sli g ht ris k of de vel o pi n g a n aller gic reacti o n. T he aller gic reacti o n ca n be 
mil d (itc hi n g, ras h) t o se vere ( diffic ult y breat hi n g, s h oc k, or rarel y, deat h). T he c o ntrast material 
ma y als o ca use ki d ne y pr o ble ms, es peciall y if y o u are de h y drate d or ha ve p o or ki d ne y f u ncti o n. 
T he st u d y d oct ors will as k y o u a b o ut a n y aller gies or relate d c o n diti o ns y o u ma y ha ve bef ore t he 
pr oce d ure is d o ne. If y o u ha ve a n y of t hese aller gies or c o n diti o ns, y o u ma y n ot be all o we d t o 
ha ve a C T sca n i n t he st u d y.
Ha vi n g a C T sca n ma y mea n s o me a d de d disc o mf ort f or y o u. I n partic ular, y o u ma y be b ot here d 
b y feeli n gs of cla ustr o p h o bia w he n place d i nsi de t he C T sca n ner, or b y l yi n g i n a still p ositi o n 
f or a l o n g ti me. If c o ntrast material is use d, y o u ma y feel disc o mf ort w he n it is i njecte d i nt o y o ur 
b o d y. Y o u ma y feel war m a n d fl us he d a n d/ or get a metallic taste i n y o ur m o ut h. Rarel y, t he 
c o ntrast material ma y ca use na usea, v o miti n g or a hea dac he.
M RI ris ks : Beca use t he M RI mac hi ne acts li ke a lar ge ma g net, it c o ul d m o ve ir o n-c o ntai ni n g 
o bjects i n t he M RI r o o m d uri n g y o ur e xa mi nati o n, w hic h i n t he pr ocess c o ul d p ossi bl y har m 
y o u. Preca uti o ns ha ve bee n ta ke n t o pre ve nt s uc h a n e ve nt fr o m ha p pe ni n g; l o ose metal o bjects, 
li ke p oc ket k ni ves or ke y c hai ns, are n ot all o we d i n t he M RI r o o m. If y o u ha ve a piece of metal 
i n y o ur b o d y, s uc h as a fra g me nt i n y o ur e ye, a ne ur ys m cli ps, ear i m pla nts, s pi nal ner ve 
sti m ulat ors, or a pace ma ker, y o u will n ot be all o we d i nt o t he M RI r o o m a n d ca n n ot ha ve a n 
M RI.
Ha vi n g a n M RI ma y mea n s o me a d de d disc o mf ort f or y o u. I n partic ular, y o u ma y be b ot here d b y 
feeli n gs of cla ustr o p h o bia a n d b y t he l o u d ba n gi n g n oise d uri n g t he st u d y. Te m p orar y heari n g 
l oss has bee n re p orte d fr o m t his l o u d n oise. T his is w h y y o u will be as ke d t o wear ear pl u gs. At 
ti mes d uri n g t he test, y o u ma y be as ke d t o n ot s wall o w f or a w hile, w hic h ca n feel 
u nc o mf orta ble.
C o ntr ast a ge nt ( g a d oli ni u m) ris ks : A fe w si de effects of ga d oli ni u m i njecti o n s uc h as 
mil d hea dac he, na usea, a n d l ocal pai n ma y occ ur. Rarel y, (less t ha n 1 % of t he ti me) l o w 
bl o o d press ure a n d li g ht hea de d ness ma y occ ur. T his ca n be treate d i m me diatel y wit h 
fl ui ds gi ve n t hr o u g h o ne of y o ur vei ns. Ver y rarel y, (less t ha n o ne i n o ne t h o usa n d), 
patie nts are aller gic t o ga d oli ni u m. T hese aller gic effects m ost c o m m o nl y i ncl u de hi ves 
a n d itc h y e yes, b ut m ore se vere reacti o ns, i ncl u di n g s h ort ness of breat h, ha ve bee n see n.
Patie nts wit h se vere ki d ne y disease s o meti mes ha ve a ba d reacti o n t o t he ga d oli ni u m 
c o ntrast material. T his c o n diti o n is calle d ne p hr o ge nic s yste mic fi br osis ( N S F). It ca n 
ca use s ki n t o ti g hte n  or scar a n d ca n da ma ge i nter nal or ga ns. S o meti mes it ca n be life-
t hreate ni n g. T here are n o re p orts of N S F i n patie nts wit h n or mal ki d ne y f u ncti o n.
Bef ore y o u ha ve a n M RI sca n re q uiri n g a n i njecti o n of ga d oli ni u m c o ntrast, y o u will 
nee d t o ha ve a bl o o d test i n or der t o c hec k t he f u ncti o n of y o ur ki d ne ys. Base d o n y o ur 
me dical hist or y a n d t he res ults of t his test, a d oct or will deci de w het her it is safe f or y o u 
t o u n der g o t he M RI sca ns.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 1 6 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
B o ne sc a n ris k : A b o ne sca n i n v ol ves e x p os ure t o ra diati o n. ( See Ra diati o n Ris ks bel o w). S o me 
pe o ple ma y ha ve a cl ose d-i n feeli n g w hile u n der t he ca mera. As i n a n y i njecti o n, y o u ma y ha ve 
s welli n g or br uisi n g at t he i njecti o n site.
R a di ati o n ris ks: T his researc h st u d y i n v ol ves e x p os ure t o ra diati o n. N ot all t his ra diati o n 
e x p os ure is necessar y f or y o ur me dical care a n d is f or researc h p ur p oses o nl y. T his a m o u nt of 
ra diati o n ma y i n v ol ve a l o w ris k of ca ncer. H o we ver, we belie ve t hat t his ris k, gi ve n y o ur o verall 
me dical c o n diti o n is n ot cli nicall y rele va nt. If y o u ha ve a n y q uesti o ns re gar di n g t he use of 
ra diati o n or t he ris ks i n v ol ve d, please c o ns ult t he p h ysicia n c o n d ucti n g t he st u d y.
Electr oc ar di o gr a m ( E K G/ E C G) ris ks: T he E C G i n v ol ves placi n g electr o des o n t he s ki n. Y o u 
ma y e x perie nce a n aller gic reacti o n t o t he a d hesi ve use d t o attac h t he electr o des t o t he s ki n. 
T hese s y m pt o ms are ge nerall y mil d a n d clear u p o n t heir o w n. Please let y o ur d oct or k n o w if y o u 
are a ware of a n y aller gies.
Ec h oc ar di o gr a m ( E C H O): T he car diac ec h o gra m mi g ht ca use y o u t o be u nc o mf orta ble fr o m 
t he press ure of t he pr o be o n y o ur c hest or l yi n g still f or t he e xa mi nati o n.
M U G A sc a n ris ks : M U G A sca ns i n v ol ve t he ris ks of ra diati o n ( See Ra diati o n Ris ks a b o ve). 
Y o u ma y de vel o p br uisi n g w here t he nee dle is place d i n y o ur vei ns t o a d mi nister t he ra di oacti ve 
s u bsta nce. Y o u ma y be u nc o mf orta ble l yi n g flat.
S afe H a n dli n g of Me dic ati o ns: Ha n dli n g ri b ocicli b a n d ha vi n g c o ntact wit h a n y uri ne, feces, or 
v o mit fr o m patie nts recei vi n g ri b ocicli b ma y p ose s o me ris k t o y o u a n d y o ur care gi vers. T o 
a v oi d e x p os ure t o ri b ocicli b a n d a n y ass ociate d ris ks, y o u a n d y o ur fa mil y me m bers/care gi vers 
will be e d ucate d b y a me m ber of t he st u d y tea m o n h o w t o safel y ha n dle, pr o perl y dis p ose of, 
a n d clea n pr o d ucts t hat ma y be c o nta mi nate d wit h ri b ocicli b.
D ose Esc al ati o n Ris ks: Si nce patie nts will be assi g ne d t o differe nt d oses of st u d y dr u g, s o me 
patie nts ma y recei ve a d ose of t he dr u g t hat is t o o s mall t o be effecti ve w hile ot hers ma y recei ve 
a hi g her d ose t hat ma y ca use i ncrease d si de effects. Y o u ca n as k y o ur st u d y d oct or w hat d ose 
y o u will be gi ve n.
Re pr o d ucti ve Ris ks: Y o u s h o ul d n ot fat her a ba b y w hile o n t his st u d y beca use t he dr u gs i n t his 
st u d y ca n affect a n u n b or n ba b y. It is i m p orta nt t o u n dersta n d t hat y o u nee d t o use birt h c o ntr ol 
w hile o n t his st u d y. Y o u m ust al wa ys wear a c o n d o m d uri n g i nterc o urse (e ve n if y o u ha ve ha d a 
vasect o m y), a n d if fertile y o u m ust als o use s per mici de. Y o u m ust c o nti n ue t o wear a c o n d o m 
w hile ta ki n g t he dr u g a n d f or 3 0 da ys after st o p pi n g treat me nt. F or m ore i nf or mati o n re gar di n g 
c o ntrace pti o n please s pea k t o y o ur st u d y d oct or.
U n k n o w n Ris ks: T he e x peri me ntal treat me nts ma y ha ve si de effects t hat n o o ne k n o ws a b o ut. 
T he researc hers will let y o u k n o w if t he y lear n a n yt hi n g t hat mi g ht ma ke y o u c ha n ge y o ur mi n d 
a b o ut partici pati n g i n t he st u d y.
F or m ore i nf or mati o n a b o ut ris ks a n d si de effects, as k y o ur st u d y d oct or.
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
Are t here be nefits t o t a ki n g p art i n t he st u d y ?
Ta ki n g part i n t his st u d y ma y or ma y n ot ma ke y o ur healt h better. W hile d oct ors h o pe t hat t he 
c o m bi nati o n of ri b ocicli b wit h d oceta xel pl us pre d nis o ne will be m ore usef ul a gai nst ca ncer 
c o m pare d t o t he us ual treat me nt, t here is n o pr o of of t his. Y o ur c o n diti o n ma y e ve n get w orse 
d uri n g t he st u d y. We d o k n o w t hat t he i nf or mati o n fr o m t his st u d y will hel p d oct ors lear n m ore 
a b o ut t heses st u d y dr u g c o m bi nati o ns as a treat me nt f or ca ncer. T his i nf or mati o n c o ul d hel p 
f ut ure ca ncer patie nts. H o we ver, t here is n o g uara ntee t hat t his will ha p pe n.
W h at ot her c h oices d o I h a ve if I d o n ot t a ke p art i n t his st u d y ?
Y o ur ot her c h oices ma y i ncl u de:

Getti n g treat me nt or care f or y o ur ca ncer wit h o ut bei n g i n a st u d y.

Ta ki n g part i n a n ot her st u d y.

Getti n g n o treat me nt.

Getti n g c o mf ort care als o calle d palliati ve care. T his t y pe of care hel ps re d uce pai n,
tire d ness, a p petite pr o ble ms a n d ot her pr o ble ms ca use d b y t he ca ncer. It d oes n ot treat t he
ca ncer directl y b ut i nstea d tries t o i m pr o ve h o w y o u feel. C o mf ort care tries t o kee p y o u
as acti ve a n d c o mf orta ble as p ossi ble.
Please tal k t o y o ur d oct or a b o ut y o ur c h oices bef ore deci di n g if y o u will ta ke part i n t his st u d y.
Will m y me dic al i nf or m ati o n be ke pt pri v ate ?
We will d o o ur best t o ma ke s ure t hat t he pers o nal i nf or mati o n i n y o ur me dical rec or d is ke pt 
pri vate. H o we ver, we ca n n ot g uara ntee t otal pri vac y. Y o ur pers o nal i nf or mati o n ma y be gi ve n 
o ut if re q uire d b y la w. If i nf or mati o n fr o m t his st u d y is p u blis he d or prese nte d at scie ntific 
meeti n gs, y o ur na me a n d ot her pers o nal i nf or mati o n will n ot be use d.
Or ga nizati o ns t hat ma y l o o k at a n d/ or c o p y y o ur me dical rec or ds f or researc h, q ualit y ass ura nce, 
a n d data a nal ysis i ncl u de:

N o vartis (t he dr u g s u p plier) a n d its a ut h orize d a ge nts

Pr ostate Ca ncer F o u n dati o n

T he U ni versit y of Calif or nia

T he Nati o nal Ca ncer I nstit ute ( N CI) a n d ot her g o ver n me nt a ge ncies, e. g., t he F o o d a n d
Dr u g A d mi nistrati o n ( F D A), i n v ol ve d i n kee pi n g researc h safe f or pe o ple. G o ver n me ntal
a ge ncies i n ot her c o u ntries w here t he st u d y dr u g ma y be c o nsi dere d f or a p pr o val.
Partici pati o n i n researc h ma y i n v ol ve a l oss of pri vac y, b ut i nf or mati o n a b o ut y o u will be 
ha n dle d as c o nfi de ntiall y as p ossi ble. A me dical rec or d will be create d beca use of y o ur 
partici pati o n i n t his st u d y. Y o ur c o nse nt f or m a n d s o me of y o ur researc h test res ults will be 
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
i ncl u de d i n t his rec or d. T heref ore, y o ur ot her d oct ors ma y bec o me a ware of y o ur partici pati o n. 
H os pital re g ulati o ns re q uire t hat all healt h care pr o vi ders treat i nf or mati o n i n me dical rec or ds 
c o nfi de ntiall y.
W h at are t he c osts of t a ki n g p art i n t his st u d y ?
St u d y dr u g (ri b ocicli b) will be pr o vi de d b y N o vartis a n d will n ot c ost y o u a n y m o ne y. Y o u 
a n d/ or y o ur healt h pla n/i ns ura nce c o m pa n y will nee d t o pa y f or d oceta xel a n d pre d nis o ne.
T w o t y pes of pr oce d ures will be d o ne d uri n g t his st u d y. S o me are part of y o ur sta n dar d me dical 
care a n d ot hers are o nl y f or researc h. Y o u or y o ur i ns urer will be bille d f or t he sta n dar d me dical 
care. Y o u will be res p o nsi ble f or y o ur c o- pa ys, de d ucti bles, a n d a n y ot her c har ges t hat y o ur 
i ns urer will n ot pa y. T here is a p ossi bilit y t hat y o ur i ns urer ma y n ot c o ver all sta n dar d me dical 
care c osts if y o u are recei vi n g me dical ser vices o ut of net w or k. A n y pr oce d ures d o ne o nl y f or 
researc h will n ot be c har ge d t o y o u or y o ur i ns urer.
Will I be p ai d f or t a ki n g p art i n t his st u d y ?
Y o u will n ot be pai d f or ta ki n g part i n t his st u d y.
W h at h a p pe ns if I a m i nj ure d bec a use I t o o k p art i n t his st u d y ?
It is i m p orta nt t hat y o u tell y o ur st u d y d oct or, Ra h ul A g gar wal, M. D., if y o u feel t hat y o u ha ve 
bee n i nj ure d beca use of ta ki n g part i n t his st u d y. Y o u ca n tell t he d oct or i n pers o n or call  
 
.
Tre at me nt a n d C o m pe ns ati o n f or I nj ur y: If y o u are i nj ure d as a res ult of bei n g i n t his 
st u d y, t he U ni versit y of Calif or nia will pr o vi de necessar y me dical treat me nt. T he c osts of 
t he treat me nt ma y be bille d t o y o u or y o ur i ns urer j ust li ke a n y ot her me dical c osts, or 
c o vere d b y t he U ni versit y of Calif or nia, de pe n di n g o n a n u m ber of fact ors. T he 
U ni versit y a n d t he st u d y s p o ns or d o n ot n or mall y pr o vi de a n y ot her f or m of
c o m pe nsati o n f or i nj ur y. F or f urt her i nf or mati o n a b o ut t his, y o u ma y call t he office of t he 
C o m mittee o n H u ma n Researc h at 4 1 5- 4 7 6- 1 8 1 4.
W h at are m y ri g hts if I t a ke p art i n t his st u d y ?
Ta ki n g part i n t his st u d y is y o ur c h oice. Y o u ma y c h o ose eit her t o ta ke part or n ot t o ta ke part i n 
t he st u d y. If y o u deci de t o ta ke part i n t his st u d y, y o u ma y lea ve t he st u d y at a n y ti me. N o matter 
w hat decisi o n y o u ma ke, t here will be n o pe nalt y t o y o u a n d y o u will n ot l ose a n y of y o ur re g ular 
be nefits. Lea vi n g t he st u d y will n ot affect y o ur me dical care. Y o u ca n still get y o ur me dical care 
fr o m o ur i nstit uti o n.
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P h as e 1 b C o ns e nt
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I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
We will tell y o u a b o ut ne w i nf or mati o n or c ha n ges i n t he st u d y t hat ma y affect y o ur healt h or 
y o ur willi n g ness t o c o nti n ue i n t he st u d y.
I n t he case of i nj ur y res ulti n g fr o m t his st u d y, y o u d o n ot l ose a n y of y o ur le gal ri g hts t o see k 
pa y me nt b y si g ni n g t his f or m.
W h o c a n a ns wer m y q uesti o ns a b o ut t he st u d y ?
Y o u ca n tal k t o y o ur st u d y d oct or a b o ut a n y q uesti o ns, c o ncer ns, or c o m plai nts y o u ha ve a b o ut 
t his st u d y. C o ntact y o ur st u d y d oct or Ra h ul A g gar wal, M. D. 
.
If y o u wis h t o as k q uesti o ns a b o ut t he st u d y or y o ur ri g hts as a researc h partici pa nt t o s o me o ne 
ot her t ha n t he researc hers or if y o u wis h t o v oice a n y pr o ble ms or c o ncer ns y o u ma y ha ve a b o ut 
t he st u d y, please call t he Office of t he C o m mittee o n H u ma n Researc h at 4 1 5- 4 7 6- 1 8 1 4.
A descri pti o n of t his cli nical trial will be a vaila ble o n htt p:// w w w. Cli nical Trials. g o v, as re q uire d 
b y U S La w. T his We b site will n ot i ncl u de i nf or mati o n t hat ca n i de ntif y y o u. At m ost, t he We b 
site will i ncl u de a s u m mar y of t he res ults. Y o u ca n searc h t his We b site at a n y ti me.
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
O P TI O N A L
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Ple ase n ote: T his secti o n of t he i nf or me d c o nse nt f or m is a b o ut a d diti o n al rese arc h st u dies 
t h at are bei n g d o ne.
Y o u c a n s a y " yes " or " n o " t o e ac h of t he f oll o wi n g st u dies. Ple ase m ar k y o ur c h oice f or 
e ac h st u d y.
Bi o m ar ker St u d y: ( o pti o nal f or P hase I b d ose escalati o n patie nts)

W hat: Bi o mar kers are i m p orta nt bi ol o gical i n dicat ors, w hic h ca n be meas ure d fr o m bl o o d
sa m ples.

W he n: Bi o mar ker sa m ples ma y be c ollecte d bef ore y o u start y o ur st u d y treat me nt

W h y: S o t hat t he researc hers ca n lear n m ore a b o ut y o ur ca ncer
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
A b o ut Usi n g S a m ples f or Rese arc h
S u bjects ta ki n g part i n t his cli nical st u d y are bei n g i n vite d t o ta ke part i n t his o pti o nal researc h 
st u d y. T his st u d y will use a n y re mai ni n g bl o o d sa m ples f or a d diti o nal researc h relate d t o t he 
ri b ocicli b, d oceta xel, pre d nis o ne, a n d/ or ca ncer.
A n y data ge nerate d fr o m t he a d diti o nal researc h st u dies will bel o n g t o U C S F a n d will n ot 
bec o me part of y o ur me dical rec or d.
Y o u ca n c h o ose n ot t o ha ve y o ur sa m ples st ore d f or a d diti o nal use a n d still be a part of t he st u d y.
Ge netic i nf or mati o n (als o k n o w n as ge n ot y pe data) a n d t he me dical rec or d data (als o k n o w n as 
p he n ot y pe data) ma y be s hare d br oa dl y i n a c o de d f or m f or f ut ure ge netic researc h or a nal ysis. 
We ma y gi ve certai n me dical i nf or mati o n a b o ut y o u (f or e xa m ple, dia g n osis, bl o o d press ure, a ge 
if less t ha n 8 5) t o ot her scie ntists or c o m pa nies n ot at U C S F, i ncl u di n g t o a ( p u blic or c o ntr olle d 
access) g o ver n me nt healt h researc h data base, b ut we will n ot gi ve t he m y o ur na me, a d dress, 
p h o ne n u m ber, or a n y ot her i de ntifia ble i nf or mati o n. Researc h res ults fr o m t hese st u dies will n ot 
be ret ur ne d t o y o u ( descri be a n y rare i nsta nces t hat t his ma y occ ur).
D o nati n g data ma y i n v ol ve a l oss of pri vac y, b ut i nf or mati o n a b o ut y o u will be ha n dle d as 
c o nfi de ntiall y as p ossi ble. St u d y data will be p h ysicall y a n d electr o nicall y sec ure d. As wit h a n y 
use of electr o nic mea ns t o st ore data, t here is a ris k of breac h of data sec urit y. Ge netic 
i nf or mati o n t hat res ults fr o m t his st u d y d oes n ot ha ve me dical or treat me nt i m p orta nce at t his 
ti me. H o we ver, t here is a ris k t hat i nf or mati o n a b o ut ta ki n g part i n a ge netic st u d y ma y i nfl ue nce 
i ns ura nce c o m pa nies a n d/ or e m pl o yers re gar di n g y o ur healt h. Ta ki n g part i n a ge netic st u d y ma y 
als o ha ve a ne gati ve i m pact or u ni nte n de d c o nse q ue nces o n fa mil y or ot her relati o ns hi ps. It is 
p ossi ble t hat f ut ure researc h c o ul d o ne da y hel p pe o ple of t he sa me race, et h nicit y, or se x as y o u. 
H o we ver, it is als o p ossi ble t hr o u g h t hese ki n ds of st u dies t hat ge netic traits mi g ht c o me t o be 
ass ociate d wit h y o ur gr o u p. I n s o me cases, t his c o ul d rei nf orce har mf ul stere ot y pes.
T here will be n o direct be nefit t o y o u fr o m all o wi n g y o ur data t o be ke pt a n d use d f or f ut ure 
researc h. H o we ver, we h o pe we will lear n s o met hi n g t hat will c o ntri b ute t o t he a d va nce me nt of 
scie nce a n d u n dersta n di n g of healt h a n d disease. If t he data or a n y ne w pr o d ucts, tests or 
disc o veries t hat res ult fr o m t his researc h ha ve p ote ntial c o m mercial val ue, y o u will n ot s hare i n 
a n y fi na ncial be nefits. If y o u deci de later t hat y o u d o n ot wa nt y o ur i nf or mati o n t o be use d f or 
f ut ure researc h, y o u ca n n otif y t he i n vesti gat or i n writi n g at 
Ra h ul A g gar wal, M D
U ni versit y of Calif or nia Sa n Fra ncisc o
a n d a n y re mai ni n g data will be destr o ye d. H o we ver, we ca n n ot retract a n y data has bee n s hare d 
wit h ot her researc hers.
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
T hi n gs t o T hi n k A b o ut
T he c h oice t o all o w U C S F t o use t he left o ver bl o o d sa m ples f or f ut ure researc h is u p t o y o u. N o 
matter w hat y o u deci de t o d o, it will n ot affect y o ur care.
If y o u deci de n o w t hat y o ur bl o o d sa m ples ca n be ke pt f or researc h, y o u ca n c ha n ge y o ur mi n d at 
a n y ti me. J ust c o ntact us a n d let us k n o w t hat y o u d o n ot wa nt us t o use y o ur sa m ples. T he n a n y 
sa m ple t hat re mai ns will n o l o n ger be use d f or researc h.
I n t he f ut ure, pe o ple w h o d o researc h ma y nee d t o k n o w m ore a b o ut y o ur healt h.
W hile U C S F ma y gi ve t he m re p orts a b o ut y o ur healt h, it will n ot gi ve t he m y o ur na me, a d dress, 
p h o ne n u m ber, or a n y ot her i nf or mati o n t hat will let t he researc hers k n o w w h o y o u are.
Y o ur sa m ples will be use d o nl y f or researc h a n d will n ot be s ol d.
T he researc h d o ne wit h y o ur bl o o d sa m ples ma y hel p t o de vel o p ne w pr o d ucts i n t he f ut ure.
Be nefits
T he researc h t hat ma y be d o ne wit h y o ur bl o o d sa m ple is n ot desi g ne d s pecificall y t o hel p y o u. It 
mi g ht hel p pe o ple w h o ha ve ca ncer a n d ot her diseases i n t he f ut ure. T he be nefits of researc h 
usi n g bl o o d sa m ple i ncl u de lear ni n g m ore a b o ut w hat ca uses ca ncer a n d ot her diseases, h o w t o 
pre ve nt t he m, a n d h o w t o treat t he m.
U C S F will be t he e xcl usi ve o w ner of a n y data a n d disc o veries res ulti n g fr o m t his researc h.
A n y c o m mercial pr o d uct de vel o pe d at U C S F as a res ult of t hese st u dies w o ul d be fr o m t he 
a nal ysis of all sa m ples c ollecte d i n t his st u d y, n ot fr o m a n i n di vi d ual s u bject’s sa m ple.
O ver all Ris k
T here is s o me ris k fr o m a breac h of c o nfi de ntialit y. We will d o o ur best t o ma ke s ure t hat y o ur 
pers o nal i nf or mati o n will be ke pt pri vate.
T he c ha nce t hat t his i nf or mati o n will be gi ve n t o s o me o ne else is ver y s mall.
If t his i nf or mati o n were release d t o y o u, y o ur fa mil y, or t hir d parties, it c o ul d p ote ntiall y be 
mis use d. S uc h mis use c o ul d lea d t o a d verse ps yc h ol o gical effects or u n desire d effects o n t he 
a bilit y of y o u or y o ur fa mil y me m bers t o o btai n a j o b or i ns ura nce.
T he t y pes of me dical i nf or mati o n t hat c o ul d be c ollecte d are y o ur pre vi o us me dical hist or y, 
la b orat or y val ues, t y pe of ca ncer, a n d t u m or sta gi n g.
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P h as e 1 b C o ns e nt
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I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
I n or der t o mi ni mize t hese p ote ntial ris ks, all researc h i nf or mati o n o btai ne d f or y o ur bl o o d 
sa m ple a n d me dical rec or ds will be ke pt c o nfi de ntial as descri be d a b o ve.
M a ki n g Y o ur C h oice
Please rea d t he se nte nces bel o w a n d t hi n k a b o ut y o ur c h oice. After rea di n g t he se nte nce, please 
p ut y o ur i nitials i n t he " Yes" or " N o" b o x. If y o u ha ve a n y q uesti o ns, please tal k t o y o ur d oct or 
or n urse, or call o ur researc h re vie w b oar d at 4 1 5- 4 7 6- 1 8 1 4.
1.
I a gree t o all o w U C S F t o st ore a n d use m y left o ver bl o o d a n d/ or t u m or s a m ples f or
a d diti o n al rese arc h tests rel ate d t o ri b ocicli b, d ocet a xel, pre d nis o ne a n d/ or c a ncer.
Y E S
N O
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
C O N S E N T
Y o u ha ve bee n gi ve n c o pies of t his c o nse nt f or m a n d t he E x peri me ntal S u bject's Bill of Ri g hts t o 
kee p.
Y o u will be as ke d t o si g n a se parate f or m a ut h orizi n g access, use, creati o n, or discl os ure of 
healt h i nf or mati o n a b o ut y o u.
P A R TI CI P A TI O N I N R E S E A R C H I S V O L U N T A R Y. Y o u ha ve t he ri g ht t o decli ne t o 
partici pate or t o wit h dra w at a n y p oi nt i n t his st u d y wit h o ut pe nalt y or l oss of be nefits t o w hic h 
y o u are ot her wise e ntitle d.
If y o u wis h t o partici pate i n t his st u d y, y o u s h o ul d si g n bel o w.
Date
Partici pa nt's Si g nat ure f or C o nse nt
Date
Partici pa nt's Pri nte d Na me
Date
Pers o n O btai ni n g C o nse nt
Date
Wit ness – O nl y re q uire d if t he partici pa nt is a n o n- E n glis h s pea ker
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P h as e 1 b C o ns e nt
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R a h ul A g g ar w al, M D
LI S T O F P R O HI BI T E D M E DI C A TI O N S
C at e g or y
Dr u g N a m e
Str o n g C Y P 3 A 4/ 5 
i n hi bit or s
At a z a n a vir/rit o n a vir, b o c e pr e vir, cl arit hr o m y ci n, c o bi ci st at, c o ni v a pt a n, 
d a n o pr e vir/rit o n a vir, d ar u n a vir/rit o n a vir, el vit e gr a vir/rit o n a vir, gr a p efr uit j ui c e, 
i d el ali si b, i n di n a vir, i n di n a vir/rit o n a vir, itr a c o n a z ol e, k et o c o n a z ol e, l o pi n a vir/rit o n a vir, 
mi b efr a dil, n ef a z o d o n e, n elfi n a vir, o m bit a s vir/ p arit a pr e vir/ d a s a b u vir/rit o n a vir 
( VI E KI R A P A K), p o s a c o n a z ol e, rit o n a vir, s a q ui n a vir/rit o n a vir, t el a pr e vir, 
t elit hr o m y ci n, ti pr a n a vir/rit o n a vir, tr ol e a n d o m y ci n v ori c o n a z ol e
Str o n g C Y P 3 A 4/ 5
i n d u c er s
c ar b a m a z e pi n e, e n z al ut a mi d e, l u m a c aft or, mit ot a n e, p h e n o b ar bit al, p h e n yt oi n, 
rif a b uti n, rif a m pi n (rif a m pi ci n), St. J o h n' s w ort ( h y p eri c u m p erf or at u m)
M e di c ati o n s wit h a
k n o w n ri s k f or Q T
pr ol o n g ati o n
A mi o d ar o n e, a n a gr eli d e, ar s e ni c tri o xi d e, a st e mi z ol e, a zit hr o m y ci n, c hl or o q ui n e, 
c hl or pr o m a zi n e, cil o st a z ol, ci pr ofl o x a ci n, ci s a pri d e, cit al o pr a m, cl arit hr o m y ci n, 
di s o p yr a mi d e, d of etili d e, d o m p eri d o n e, d o n e p e zil, dr o n e d ar o n e, dr o p eri d ol, 
er yt hr o m y ci n, e s cit al o pr a m, fl e c ai ni d e, fl u c o n a z ol e, g atifl o x a ci n e, gr e p afl o x a ci n, 
h al of a ntri n e, h al o p eri d ol, i b utili d e, l e v ofl o x a ci n, l e v o m e pr o m a zi n e, l e v o s ul piri d e, 
m et h a d o n e, m o xifl o x a ci n, o n d a n s etr o n, o x ali pl ati n, p a p a v eri n e H Cl (i ntr a- c or o n ar y), 
p e nt a mi di n e, pi m o zi d e, pr o c ai n a mi d e, pr o p of ol, q ui ni di n e, r o xit hr o m y ci n, 
s e v ofl ur a n e, s ot al ol, s ul piri d e, s ult o pri d e, t erli pr e s si n, t er o dili n e, t hi ori d a zi n e, 
v a n d et a ni b
C Y P 3 A 4/ 5 
s u b str at e s wit h N TI
Alf e nt a nil, a st e mi z ol e, ci s a pri d e, c y cl o s p ori n e, di er g ot a mi n e ( di h y dr o er g ot a mi n e), 
er g ot a mi n e, f e nt a n yl, pi m o zi d e, q ui ni di n e, sir oli m u s, t a cr oli m u s
Ot h er 
i n v e sti g ati o n al a n d 
a nti n e o pl a sti c 
t h er a pi e s n ot p art of 
t h e st u d y
Ot h er i n v e sti g ati o n al t h er a pi e s m u st n ot b e u s e d w hil e t h e p ati e nt i s o n t h e st u d y. 
A nti c a n c er t h er a p y ( c h e m ot h er a p y, all S E R M S (i n cl u di n g r al o xif e n e) bi ol o gi c or 
r a di ati o n t h er a p y, a n d s ur g er y) ot h er t h a n t h e st u d y tr e at m e nt s m u st n ot b e gi v e n t o 
p ati e nt s w hil e t h e p ati e nt i s o n t h e st u d y m e di c ati o n. If s u c h a g e nt s ar e r e q uir e d f or a 
p ati e nt, t h e n t h e p ati e nt m u st b e di s c o nti n u e d fr o m t h e st u d y.
H er b al 
pr e p ar ati o n s/ 
m e di c ati o n s
H er b al pr e p ar ati o n s/ m e di c ati o n s ar e pr o hi bit e d t hr o u g h o ut t h e st u d y. T h e s e h er b al 
m e di c ati o n s i n cl u d e, b ut ar e n ot li mit e d t o bl a c k c o h o s h, St. J o h n’ s W ort, K a v a, 
e p h e dr a ( m a h u a n g), gi n g k o bil o b a, d e h y dr o e pi a n dr o st er o n e ( D H E A), y o hi m b e, s a w 
p al m ett o, a n d gi n s e n g. P ati e nt s s h o ul d st o p u si n g t h e s e h er b al m e di c ati o n s 7 d a y s 
pri or t o fir st d o s e of st u d y dr u g.
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 2 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
LI S T O F M E DI C A TI O N S T O B E U S E D WI T H C A U TI O N
C at e g or y
Dr u g N a m e
M o d er at e 
C Y P 3 A 4/ 5 
i n hi bit or s
A pr e pit a nt, a m pr e n a vir, a s af o eti d a r e si n ( F er ul a a s af o eti d a) ci m eti di n e, cri z oti ni b, 
dilti a z e m, f al d a pr e vir, i m ati ni b, i s a v u c o n a z ol e, n et u pit a nt, nil oti ni b, t ofi s o p a m, 
S c hi s a n dr a s p h e n a nt h er a ( n a n w u w ei zi), v er a p a mil
M o d er at e
C Y P 3 A 4/ 5
i n d u c er s
B o s e nt a n, d a br af e ni b, ef a vir e n z, etr a viri n e, g e ni st ei n,l o pi n a vir 5 , m o d afi nil, n af cilli n, 
t el otri st at
S e n siti v e
C Y P 3 A 4/ 5
s u b str at e s
Al p h a- di h y dr o er g o cr y pti n e, a pr e pit a nt, at or v a st ati n, a v a n afil, b o s uti ni b, br oti z ol a m, 
b u d e s o ni d e, b u s pir o n e, c o bi m eti ni b, d arif e n a ci n, d a s ati ni n b, e b a sti n e, el etri pt a n, 
e pl er e n o n e, e v er oli m u s, f el o di pi n e, fl uti c a s o n e, gr a z o pr e vir, i br ut ni b, i s a v u c o n a z ol e, 
i v a br a di n e, i v a c aft or, , l e v o m et h a d yl ( L A A M), l o mit a pi d e, l o v a st ati n, l u m ef a ntri n e, 
l ur a si d o n e, m ar a vir o c, mi d a z ol a m, mi d o st a uri n, n al o x e g ol, n er ati ni b, ni s ol di pi n e, 
p er o s pir o n e, q u eti a pi n e, ri d af or oli m u s, sil d e n afil, si m e pr e vir, si m v a st ati n, ti c a gr el or, 
tili di n e, t ol v a pt a n, tri a z ol a m, uli pri st al, v ar d e n afil, v e n et o cl a x, vi cri vir o c, v o cl o s p ori n
B S E P i n hi bit or s
Al e cti ni b, at or v a st ati n, br o m o cri pti n e, c a n d e s art a n, cl o b et a s ol, cl of a zi mi ni e, d a bi g atr a n, 
di p yri d a m ol e, gl y b uri d e, gr a z o pr e vir, l e di p a s vir, mif e pri st o n e, pi o glit a z o n e, 
r e s er pi n e,rif a m y ci n, si m e pr e vir, t el mi s art a n,ti m c o d ar, tr o glit a z o n e, v ali n o m y ci n, 
v el p at a s vir
M A T E 1 a n d 
O C T 2 s u b str at e s
A c y cl o vir, c e p h al e xi n, ci m eti di n e, f e x of e n a di n e, g a n ci cl o vir, gl y c o p yrr o ni u m, m etf or mi n, 
pi n d ol ol, pli si c ai ni d e, r a niti di n e, t o p ot e c a n, v ar e ni cli n e
O C T 1/ 2 
s u b str at e s
A m a nt a di n e, 6- b et a- h y dr o x y c orti s ol, c ar b o pl ati n, ci s pl ati n, c e p h al e xi n, c e p hr a di n e, 
i pr atr o pi u m, l a mi v u di n e, li n a gli pti n, m etf or mi n, o x y pl ati n, o x y b ut y ni n, p h e nf or mi n, 
pi c o pl ati n, pil si c ai ni d e, pi n d ol ol, r a niti di n e, s or af e ni b, tr o pi s etr o n, tr o s pi u m, 
u m e cli di ni u m, a n d zi d o v u di n e
B C R P s u b str at e s D a u n or u bi ci n, d ol ut e gr a vir, d o x or u bi ci n, h e m at o p or p h yri n, i m ati ni b, m et h otr e x at e, 
mit o x a ntr o n e, pit a v a st ati n, r o s u v a st ati n, iri n ot e c a n, et hi n yl e str a di ol, si m v a st ati n, 
s ulf a s al a zi n e, s of o s b u vir, t e n of o vir, t o p ot e c a n, v e n et o cl a x
M e di c ati o n s t h at 
c arr y a p o s si bl e 
ri s k f or Q T 
pr ol o n g ati o n
Alf u z o si n, a p o m or p hi n e, ari pi pr a z ol e, art e ni m ol + pi p er a q ui n e , a s e n a pi n e, at o m o x eti n e, 
b e d a q uili n e, b e n d a m u sti n e, b ort e z o mi b, b o s uti ni b, b u pr e n or p hi n e, c a b o z a nti ni b, 
c a p e cit a bi n e, c eriti ni b, cl o mi pr a mi n e, cri z oti ni b, cl o z a pi n e, c y a m e m a zi n e 
( c y a m e pr o m a zi n e), d a br af e ni b, d a s ati ni b, d e g arili x, d el a m a ni d, d e si pr a mi n e, 
d e x m e d et o mi di n e, d ol a s etr o n, ef a vir e n z, eli gl u st at, e pir u bi ci n, eri b uli n m e s yl at e, 
e z o g a bi n e(r eti g a bi n e), f a m oti di n e, f el b a m at e, fi n g oli m o d, fl u p e nti x ol, g e mifl o x a ci n, 
gr a ni s etr o n, h y dr o c o d o n e- E R, il o p eri d o n e, i mi pr a mi n e ( m eli pr a mi n e), i sr a di pi n e, 
k et a n s eri n, l a p ati ni b, l e n v ati ni b, l e u pr oli d e, lit hi u m, m el p er o n e, mi d o st a uri n, 
mif e pri st o n e, mir a b e gr o n, mirt a z a pi n e, m o e xi pril/ H C T Z, n e cit u m u m a b, ni c ar di pi n e, 
nil oti ni b, n orfl o x a ci n, n ortri pt yli n e, n u si n er s e n, ofl o x a ci n, o si m erti ni b, o x yt o ci n, 
p ali p eri d o n e, p al o n o s etr o n, p a n a bi n o st at, p a sir e oti d e, p a z o p a ni b, p erfl utr e n li pi d 
mi cr o s p h er e s, p er p h e n a zi n e, pil si c ai ni d e, pi m a v a n s eri n, pi p a m p er o n e, pr o m et h a zi n e, 
pr ot hi p e n d yl, ril pi viri n e, ri s p eri d o n e, r o mi d e p si n, s erti n d ol e, s or af e ni b, s u niti ni b, 
t a m o xif e n, ti pir a cil/trifl uri di n e, ti z a ni di n e, t olt er o di n e, t or e mif e n e,tri mi pr a mi n e, 
tr o pi s etr o n, v ar d e n afil, v e m ur af e ni b, v e nl af a xi n e, v ori n o st at, zi pr a si d o n e
I R B N U M B E R: 1 5- 1 5 7 4 5
I R B A P P R O V A L D A T E: 0 7/ 2 6/ 2 0 1 9
I R B E X PI R A TI O N D A T E: 0 2/ 1 1/ 2 0 2 0


P h as e 1 b C o ns e nt
P a g e 2 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
T his will be t he first ti me t hat all t hree dr u gs, ri b ocicli b, d oceta xel, a n d pre d nis o ne are use d i n 
c o m bi nati o n t o treat patie nts.
N o vartis P har mace uticals, I nc. w hic h ma n ufact urers ri b ocicli b is s u p pl yi n g t he st u d y dr u g free-
of-c har ge a n d is pr o vi di n g s u p p ort t o t he i n vesti gat or a n d t he i nstit uti o n t o c o n d uct t he st u d y. 
T he Pr ostate Ca ncer F o u n dati o n is als o pr o vi di n g f u n di n g f or t his st u d y.
H o w m a n y pe o ple will t a ke p art i n t his st u d y ?
T here are t w o parts t o t his st u d y; a d ose-fi n di n g part ( p hase I b) a n d a d ose e x pa nsi o n/ p hase II 
part, y o u will o nl y be partici pati n g i n t he d ose-fi n di n g part ( p hase I b). A p pr o xi matel y 9- 1 8 
patie nts will partici pate i n t he d ose-fi n di n g part ( p hase I b) at U C S F.
W h at will h a p pe n if I t a ke p art i n t his rese arc h st u d y ?
Y o u will recei ve o ne of t hree d osa ges of ri b ocicli b, i n c o m bi nati o n wit h a sta n dar d d ose of 
d oceta xel a n d pre d nis o ne. Gr o u ps of t hree t o si x patie nts will recei ve treat me nt at a gi ve n d osa ge 
le vel of ri b ocicli b. If, d uri n g t he first 2 8 da ys of treat me nt, fe w seri o us si de effects are o bser ve d, 
a ne w gr o u p of t hree t o si x patie nts will j oi n t he st u d y. Eac h gr o u p of patie nts will be treate d 
wit h t he sta n dar d d ose of d oceta xel a n d pre d nis o ne, gi ve n t o get her wit h i ncreasi n g d oses of 
ri b ocicli b, u ntil t he hi g hest t olera ble d oses are i de ntifie d.
Y o u will be treate d wit h t he c o m bi nati o n of ri b ocicli b pl us d oceta xel + pre d nis o ne f or u p t o 9 
c ycles. If t here is n o e vi de nce of pr o gressi o n after 9 c ycles, y o u ma y c o nti n ue o n si n gle a ge nt 
mai nte na nce ri b ocicli b u ntil t he ti me of disease pr o gressi o n. T he d ose of ri b ocicli b use d d uri n g 
mai nte na nce will be t he sa me d ose as t hat i m me diatel y prece di n g cessati o n of d oceta xel 
treat me nt.
W hic h d ose of ri b ocicli b y o u recei ve will de pe n d o n t he pr o gress of t he st u d y a n d t he si de 
effects see n wit h ot her patie nts o n t he st u d y. Y o u will n ot be a ble t o c h o ose w hic h d ose of 
ri b ocicli b y o u recei ve.
Y o u will be as ke d if y o u all o w f urt her researc h t o be perf or me d o n left o ver t u m or sa m ples. 
W het her or n ot y o u a gree t o t his o pti o nal researc h will n ot affect y o ur a bilit y t o partici pate i n t he 
mai n p orti o n of t he st u d y. Please refer t o t he e n d of t his c o nse nt f or m f or a n y i nf or mati o n a b o ut 
o pti o nal researc h.
D osi n g a d mi nistr ati o n i nstr ucti o ns:

D oceta xel will be a d mi nistere d t hr o u g h o ne of y o ur vei ns o n t he first da y of eac h 3- wee k
treat me nt c ycle.

Pre d nis o ne will be ta ke n orall y t wice dail y e ver y da y of eac h 3- wee k c ycle.


P h as e 1 b C o ns e nt
P a g e 3 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Ri b ocicli b will be ta ke n orall y o nce dail y o n da ys 1- 4 a n d 8- 1 5 of eac h 3- wee k c ycle.

Fil grasti m (als o calle d Ne u p o ge n) will be a d mi nistere d u n der t he s ki n o n da ys 5- 7 of
eac h 3- wee k c ycle as well as a d diti o nal d oses as nee de d.

O n m ost da ys, y o u will ta ke st u d y dr u gs at h o me. O n t he da ys y o u c o me t o cli nic, y o u
will wait t o ta ke t he st u d y dr u gs d uri n g t he visit o nce y o u are i nstr ucte d t o d o s o.

Y o u s h o ul d s wall o w ri b ocicli b ca ps ules wit h a lar ge glass of water at t he sa me ti me eac h
m or ni n g.

Y o u s h o ul d s wall o w t he ri b ocicli b ca ps ules w h ole a n d n ot c he w, cr us h, or o pe n t he m.

Y o u s h o ul d ta ke pre d nis o ne ta blets i n t he m or ni n g a n d mi d-after n o o n wit h f o o d.

If y o u v o mit after ta ki n g a d ose, d o n ot re peat t he d ose.

D o n ot miss a n y d oses. If y o u f or get t o ta ke y o ur st u d y dr u gs b ut re me m ber wit hi n si x
h o urs of w he n y o u were s u p p ose d t o ta ke t he m, y o u s h o ul d ta ke t he dr u gs. If it is m ore
t ha n si x h o urs, y o u s h o ul d s ki p t he m.

T he st u d y d oct or will i nstr uct y o u o n h o w ma n y ca ps ules or ta blets of eac h dr u g y o u
s h o ul d ta ke.

A v oi d c o ns u m pti o n of gra pefr uit, Se ville ora n ges, p o mel os, a n d star fr uit or pr o d ucts
c o ntai ni n g t he j uice of eac h (i ncl u di n g ja ms a n d mar mala des) d uri n g t he st u d y a n d f or 7
da ys pri or t o t he first d ose of ri b ocicli b. Re g ular ora n ge j uice is all o we d.
Bef ore y o u be gi n t he m ai n p art of t he st u d y:
Y o u will nee d t o ha ve t he f oll o wi n g e xa ms, tests or pr oce d ures t o fi n d o ut if y o u ca n be i n t he 
mai n part of t he st u d y. Ma n y of t hese e xa ms, tests or pr oce d ures are part of re g ular r o uti ne 
ca ncer care a n d ma y be d o ne e ve n if y o u d o n ot j oi n t he st u d y. If y o u ha ve ha d s o me of t he m 
rece ntl y, t he y ma y n ot nee d t o be re peate d. T his will be u p t o y o ur st u d y d oct or. T he t otal ti me t o 
c o m plete t he scree ni n g tests a n d pr oce d ures is a b o ut 8- 1 2 h o urs. T he f oll o wi n g pr oce d ures will 
be d o ne:

A c o m plete me dic al hist or y a n d y o ur c urre nt me dic al c o n diti o n will be c ollecte d
i ncl u di n g i nf or mati o n a b o ut y o ur c urre nt healt h stat us

P h ysical E xa mi nati o n

Vit al si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht a n d wei g ht

Bl o o d s a m ples: A bl o o d sa m ple will be dra w n b y i nserti n g a nee dle i nt o a vei n i n y o ur
ar m ( ~ 4 ta bles p o o ns of bl o o d):
o
C o m plete bl o o d c o u nt ( C B C) wit h differe ntial a n d platelet c o u nt
o
Bl o o d c he mistr y assess me nt
o
P S A
o
Test oster o ne

T o meas ure y o ur disease, y o u will ha ve o ne or m ore of t he f oll o wi n g tests d o ne (t hese
will be d o ne wit hi n 4 2 da ys of re gistrati o n):

C T a n d/ or M RI sca n of t he c hest, a b d o me n, a n d pel vis :


P h as e 1 b C o ns e nt
P a g e 4 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

B o ne sc a n: A b o ne sca n is a test t hat ma kes detaile d i ma ges of y o ur b o nes a n d a n y
t u m ors o n t he m. Bef ore t he b o ne sca n, a s mall a m o u nt of ra di oacti ve s u bsta nce is
i njecte d i nt o y o ur vei n. A b o ut 3 h o urs later, y o u will lie o n a ta ble u n der a mac hi ne,
w hic h will ma ke a n i ma ge of y o ur b o nes. T he test itself will ta ke a b o ut 1 h o ur, b ut t he
w h ole pr ocess ta kes u p t o 4 h o urs.

Electr oc ar di o gr a m ( E C G): rec or ds t he electrical acti vit y of y o ur heart. Wires or “lea ds”
will be attac he d t o y o ur c hest wit h a n a d hesi ve a n d y o u will be as ke d t o lie still w hile t he
mac hi ne pri nts o ut a n electrical “rec or d” of y o ur heart acti vit y. T he pr oce d ure is d o ne i n
t he Car di ol o g y De part me nt a n d ta kes a b o ut 1 5- 3 0 mi n utes.

Y o u will be as ke d a b o ut a n y me dici nes y o u are ta ki n g i ncl u di n g o ver-t he-c o u nter
me dici nes, vita mi ns, or her bal treat me nts.

Perf or m a nce st at us t o assess h o w y o ur disease is affecti n g y o ur dail y acti vities.

Eit her a M U G A ( m ulti ple- gate d ac q uisiti o n) sca n or a n E C H O (ec h ocar di o gra m), n o n- 
i n vasi ve tests w hic h ta ke m o vi n g pict ures of y o ur heart will als o be d o ne. T hese will be
d o ne wit hi n 4 2 of re gistrati o n.
o
M U G A sc a n : A M U G A sca n is a test t hat ma kes a m oti o n pict ure t hat s h o ws h o w
well y o ur heart p u m ps bl o o d. T he sca n is perf or me d b y ta ki n g a s mall sa m ple of
o
A C T sc a n is a ra di ol o gical test t hat uses s pecial x-ra y e q ui p me nt t o ma ke detaile d
pict ures of b o d y tiss ues a n d or ga ns. F or t he C T sca n, y o u ma y be gi ve n a  “c o ntrast
material" (a s pecial d ye t hat ma kes it easier f or d oct ors t o see differe nt  tiss ues i n y o ur
b o d y). T he c o ntrast material ma y be gi ve n orall y or t hr o u g h o ne of  y o ur vei ns. Oral
c o ntrast material is gi ve n t o y o u t o dri n k a n d is use d t o hel p  o utli ne t he st o mac h a n d
i ntesti nes. I ntra ve n o us (I V) c o ntrast material is gi ve n t o y o u b y i njecti n g t he c o ntrast
material i nt o a li ne, w hic h is attac he d t o a nee dle i n  y o ur ar m a n d is use d t o get clearer
pict ures of y o ur b o d y ca vit y. After y o u ha ve  bee n gi ve n t he c o ntrast material (eit her b y
m o ut h, b y vei n), y o u will lie flat o n a  ta ble t hat will m o ve y o u i nt o t he C T sca n
mac hi ne. Y o u will be as ke d t o lie still  a n d ma y be as ke d t o h ol d y o ur breat h f or a fe w
sec o n ds. Eac h C T sca n will ta ke a b o ut 1 5 mi n utes t o a half h o ur.
If a C T sca n ca n n ot be perf or me d, a n M RI sc a n will be perf or me d. A n M RI sca n  ta kes
a n i ma ge of y o ur b o d y t o o bser ve t he l ocati o n a n d size of y o ur t u m or. F or  t he M RI
sca n, y o u ma y be gi ve n a "c o ntrast material" (a s pecial d ye t hat ma kes it easier f or
d oct ors t o  see differe nt tiss ues i n y o ur b o d y). Ga d oli ni u m is c o ntrast material t hat
ca uses s o me t u m ors t o a p pear m uc h bri g hter t ha n n or mal tiss ue o n  M RI sca ns t hese
t u m ors ma y n ot be visi ble wit h o ut ga d oli ni u m). T he c o ntrast  material ma y be gi ve n t o
y o u i n y o ur ar m t hr o u g h a cat heter (a ti n y t u be) i nserte d  i nt o a vei n. Y o u will t he n lie
d o w n o n a narr o w be d, w hic h will be place d i n a  t u n nel t hat is 6 feet l o n g b y 2 2 i nc hes
wi de a n d o pe n at eac h e n d. Y o u will lie t here q uietl y f or a b o ut o ne h o ur, d uri n g w hic h
ti me y o u will hear a l o u d mac hi ne- li ke n oise. T he M RI sca n is d o ne i n t he Ra di ol o g y
De part me nt a n d ta kes  a p pr o xi matel y a n h o ur a n d a half t o c o m plete.


P h as e 1 b C o ns e nt
P a g e 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
y o ur o w n bl o o d t hat is t he n “la bele d” wit h a ra di oacti ve s u bsta nce. T he la bele d 
bl o o d sa m ple is t he n re-i njecte d i nt o a vei n i n y o ur ar m a n d all o we d t o circ ulate 
i n y o ur b o d y. O nce t he la bele d bl o o d has circ ulate d ar o u n d y o ur b o d y, a series of 
i ma ges (si milar t o a m o vie) are ta ke n of y o ur heart. Y o u will be as ke d t o lie flat 
o n a ta ble a n d re mai n still f or a b o ut 1 0- 2 0 mi n utes w hile t he pict ures of y o ur 
heart are bei n g ta ke n. T his test is d o ne i n t he N uclear Me dici ne de part me nt a n d 
ta kes a b o ut 9 0 mi n utes.
o
E C H O : T his e xa mi nati o n uses s o u n d wa ves t o ma ke pict ures of y o ur heart,
w hic h hel ps deter mi ne h o w well y o ur heart s q ueezes bl o o d. Y o u will be as ke d t o
lie o n y o ur left si de w hile a tec h nicia n places a pr o be wit h gel o n y o ur c hest t o
create i ma ges of y o ur heart t o deter mi ne t he f u ncti o n a n d size. T he pr oce d ure is
d o ne i n t he Car di ol o g y De part me nt a n d will ta ke a p pr o xi matel y 4 5- 6 0 mi n utes.
D uri n g t he m ai n p art of t he st u d y:
If t he e xa ms, tests, a n d pr oce d ures s h o w t hat meet t he criteria t o be i n t he researc h st u d y a n d y o u 
c h o ose t o ta ke part, y o u will t he n be e nr olle d i n t he researc h st u d y. Eac h c ycle of treat me nt will 
last 2 1 da ys.
C ycle 1, D a y 1 (t his visit will t a ke a b o ut 4 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Start ta ki n g oral pre d nis o ne t wice dail y

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns

First oral d ose of ri b ocicli b

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
P har mac o ki netics – T hese are bl o o d tests t hat will hel p deter mi ne t he le vels of
st u d y dr u g i n y o ur bl o o d at differe nt ti me p oi nts.
C ycle 1, D a y 2 (t his visit will t a ke a b o ut 3 0 mi n utes) 

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Re vie w of si de effects


P h as e 1 b C o ns e nt
P a g e 6 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Perf or ma nce stat us

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
P har mac o ki netics – T hese are bl o o d tests t hat will hel p deter mi ne t he le vels of
st u d y dr u g i n y o ur bl o o d at differe nt ti me p oi nts.
C ycle 1, D a ys 5- 7 (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)

Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will
be a d mi nistere d eit her at h o me or i n t he cli nic.
C ycle 1, D a y 8 (t his visit will t a ke a b o ut 1 h o ur)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 1, D a y 1 5 (t his visit will t a ke a b o ut 1 h o ur)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure)

Electr ocar di o gra m ( E C G)

Bl o o d sa m ples ( ~ 1 ta bles p o o n of bl o o d):
o
Bl o o d c o u nts

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 2, D a y 1 (t his visit will t a ke a b o ut 1 – 1 1/ 2 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Electr ocar di o gra m ( E C G)

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts


P h as e 1 b C o ns e nt
P a g e 7 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns
C ycle 2, D a ys 5- 7 (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)
Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will be 
a d mi nistere d eit her at h o me or i n t he cli nic.
D a y 1 of E ver y C ycle T here after (t his visit will t a ke a b o ut 4 h o urs)

P h ysical E xa mi nati o n

Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht

Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

A d mi nistrati o n of d oceta xel t hr o u g h o ne of y o ur vei ns

Re vie w of si de effects

Electr ocar di o gra m ( E C G)

Perf or ma nce stat us

C o nc urre nt me dicati o ns
D a ys 5- 7 of E ver y C ycle T here after (t his visit s h o ul d t a ke a b o ut 1 5 mi n utes)

Ne u p o ge n a d mi nistrati o n – gi ve n u n der t he s ki n dail y o n Da ys 5- 7. T hese i njecti o ns will
be a d mi nistere d eit her at h o me or i n t he cli nic.
St arti n g C ycle 4 a n d E ver y 3 Tre at me nt C ycles (t his visit will t a ke a b o ut 5 h o urs)
T he f oll o wi n g will be d o ne as part of y o ur r o uti ne care:

C T or M RI of t he c hest/a b d o me n/ pel vis

B o ne sca n


P h as e 1 b C o ns e nt
P a g e 8 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
E n d of Tre at me nt Visit (t his visit will t a ke bet wee n 1 h o ur a n d 5 h o urs)
D uri n g t his visit, y o u will ha ve t he f oll o wi n g e xa ms, tests, or pr oce d ures at t he ti me, as 
s pecifie d. T he visit will be d o ne wit hi n 3 0 da ys of t he last treat me nt.
•
P h ysical E xa mi nati o n
•
Vital si g ns ( bl o o d press ure, heart rate, te m perat ure), hei g ht, a n d wei g ht
•
Bl o o d sa m ples ( ~ 2 ta bles p o o ns of bl o o d):
o
Bl o o d c o u nts
o
R o uti ne tests f or safet y
o
P S A

Re vie w of si de effects

Perf or ma nce stat us

C o nc urre nt me dicati o ns

C T or M RI of t he c hest/a b d o me n/ pel vis (if n ot alrea d y c o m plete d wit hi n past 2 8 da ys)

B o ne sca n (if n ot alrea d y c o m plete d wit hi n past 2 8 da ys)
Y o u will be c o nt acte d 3 0 d a ys after t he l ast d ose of st u d y tre at me nt . Y o u will be as ke d h o w 
y o u are feeli n g a n d w hat me dicati o ns y o u ha ve bee n ta ki n g.
If y o u wit h dr a w fr o m t he st u d y, a n d y o ur disease has n ot pr o gresse d, y o u ma y be c o ntacte d via 
a p h o ne call, a n d as ke d t o ha ve a C T/ M RI sca n d o ne e ver y t w o m o nt hs t o meas ure y o ur disease 
si nce st o p pi n g st u d y treat me nt. T his will be d o ne f or researc h p ur p oses if t his sca n is d o ne at a 
ti me p oi nt ot her t ha n y o ur r o uti ne resta gi n g ti me p oi nt.
Wit h dr a w al of y o ur c o nse nt t o p artici p ate i n t his st u d y
Y o u ma y deci de t hat y o u n ot o nl y wa nt t o st o p st u d y treat me nt b ut als o d o n ot wa nt t o c o me t o 
a n y f urt her visits, a n d d o n ot wa nt t o ha ve a n y f urt her assess me nts or c o ntact b y t he st u d y staff.
T his is c o nsi dere d as wit h dra wal of y o ur c o nse nt fr o m partici pati o n i n t his st u d y. It is i m p orta nt 
t hat y o u i nf or m y o ur St u d y D oct or.
U C S F will c o nti n ue t o retai n a n d use a n y researc h-relate d res ults t hat ha ve alrea d y bee n 
c ollecte d f or t he st u d y e val uati o n. N o f urt her st u d y-relate d acti vities will ta ke place.
Y o u ca n disc uss f urt her re g ular me dical care wit h y o ur St u d y D oct or. T he c h oice t o wit h dra w 
fr o m researc h partici pati o n will n ot affect y o ur me dical care.
St u d y l oc ati o n: All st u d y pr oce d ures will be d o ne at U C S F Hele n Diller Fa mil y C o m pre he nsi ve 
Ca ncer Ce nter.


P h as e 1 b C o ns e nt
P a g e 9 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
W h at Will I Be As ke d t o D o W hile P artici p ati n g I n T he St u d y ?
I n or der f or t his st u d y t o pr o vi de g o o d i nf or mati o n a b o ut h o w t he dr u gs w or k, y o u will be as ke d 
t o d o t he f oll o wi n g:

C o m pl y wit h y o ur st u d y d oct or’s i nstr ucti o ns. Please n ote: It is ver y i m p orta nt t hat y o u
ta ke t he me dici ne gi ve n t o y o u j ust as t he d oct or tells y o u t o. D o n ot miss a n y d oses a n d
d o n ot tr y t o d o u ble t he d ose if y o u miss a d ose.

N otif y y o ur st u d y d oct or i m me diatel y of a n y i nj ur y or u n us ual s y m pt o ms d uri n g y o ur
partici pati o n i n t his st u d y.

Re vie w all t he healt h f o o d s u p ple me nts, o ver-t he-c o u nter a n d prescri pti o n me dicati o ns
wit h y o ur st u d y d oct or bef ore ta ki n g t he m.

Wit h t he e xce pti o n of e mer ge ncies, y o u s h o ul d n ot ta ke ot her dr u gs w hile y o u are
partici pati n g i n t he st u d y wit h o ut ha vi n g c o ns ulte d y o ur st u d y d oct or. I n case of a n
e mer ge nc y treat me nt, y o ur st u d y d oct or s h o ul d be i nf or me d i m me diatel y.

Bri n g all of y o ur e xtra st u d y dr u g me dicati o n a n d e m pt y pill b ottles bac k t o t he st u d y
d oct or.

D o n ot eat or dri n k gra pefr uit, Se ville (s o ur/ bl o o d) ora n ges or pr o d ucts c o ntai ni n g t he
j uice of eac h d uri n g t he st u d y, as t hese fr uits a n d t heir j uice ca n i nterfere wit h t he bl o o d
le vels of t he dr u gs. Re g ular ora n ge j uice is o ka y.

O n t he da ys t hat y o u c o me t o cli nic visits, y o u will ta ke t he st u d y dr u g t here. After war d,
y o u will be pr o vi de d wit h e n o u g h st u d y me dicati o n u ntil y o ur ne xt pla n ne d cli nic visit.

Y o u will be as ke d t o rec or d t he date a n d ti me y o u t o o k t he st u d y me dicati o n a n d a n y si de
effects y o u ma y e x perie nce i n a diar y. T his diar y m ust be ret ur ne d t o y o ur st u d y d oct or at
y o ur ne xt visit.

D uri n g t he w h ole d urati o n of treat me nt o n t his st u d y, y o u are n ot all o we d t o partici pate i n
a n ot her cli nical st u d y t hat ma y i nterfere wit h t his st u d y. If y o u are i ntereste d i n
partici pati n g i n a n ot her st u d y, y o u m ust s pea k t o y o ur st u d y d oct or a b o ut it.
H o w l o n g will I be i n t he st u d y ?
Y o u will c o nti n ue st u d y treat me nt u ntil y o u e x perie nce disease pr o gressi o n, disc o nti n ue 
treat me nt d ue t o i nt olera ble t o xicit y, i n vesti gat or decisi o n, or wit h dra w c o nse nt, w hic he ver 
occ urs first. Y o u will be treate d wit h t he c o m bi nati o n of ri b ocicli b pl us d oceta xel + pre d nis o ne 
f or u p t o 9 c ycles. If t here is n o e vi de nce of disease pr o gressi o n after 9 c ycles of pr ot oc ol 
t hera p y, patie nts ma y c o nti n ue o n si n gle a ge nt mai nte na nce ri b ocicli b u ntil t he ti me of disease 
pr o gressi o n.
Y o ur d oct or ca n als o deci de t o wit h dra w y o u fr o m t he st u d y if he/s he feels t hat t his is best f or 
y o u.


P h as e 1 b C o ns e nt
P a g e 1 0 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
C a n I st o p bei n g i n t he st u d y ?
Yes. Y o u ca n deci de t o st o p at a n y ti me. Tell t he st u d y d oct or if y o u are t hi n ki n g a b o ut st o p pi n g 
or deci de t o st o p. S he will tell y o u h o w t o st o p y o ur partici pati o n safel y.
It is i m p orta nt t o tell t he st u d y d oct or if y o u are t hi n ki n g a b o ut st o p pi n g s o a n y ris ks ca n be 
e val uate d b y y o ur d oct or. A n ot her reas o n t o tell y o ur d oct or t hat y o u are t hi n ki n g a b o ut st o p pi n g 
is t o disc uss w hat f oll o w- u p care a n d testi n g c o ul d be m ost hel pf ul f or y o u.
T he st u d y d oct or ma y st o p y o u fr o m ta ki n g part i n t his st u d y at a n y ti me if s he belie ves it is i n 
y o ur best i nterest, if y o u d o n ot f oll o w t he st u d y r ules, or if t he st u d y is st o p pe d.
W h at si de effects or ris ks c a n I e x pect fr o m bei n g i n t he st u d y ?
Ris ks are p ossi ble si de effects of st u d y me dici ne, or u n der g oi n g tests, s uc h as i ma gi n g sca ns a n d 
bl o o d or t u m or sa m ple c ollecti o n.
T he p ote ntial si de effects descri be d bel o w f or ri b ocicli b are base d o n tests i n a ni mals a n d 
e x perie nce i n ca ncer s u bjects. It is p ossi ble t hat y o u ma y e x perie nce si de effects t hat are 
u ne x pecte d a n d u nf oresee n. E ver y o ne ta ki n g part i n t he st u d y will be watc he d caref ull y f or a n y 
si de effects. Pre ve nti n g si de effects, w he n p ossi ble, is a n i m p orta nt part of all ca ncer care.
T he p ote ntial si de effects descri be d bel o w f or ri b ocicli b a n d B Y L 7 1 9 are base d o n tests i n 
a ni mals a n d e x perie nce i n ca ncer patie nts. T he p ote ntial si de effects descri be d bel o w f or 
letr oz ole are base d o n e xte nsi ve e x perie nce i n ca ncer patie nts. It is p ossi ble t hat y o u ma y 
e x perie nce si de effects t hat are t otall y u ne x pecte d a n d u nf oresee n. E ver y o ne ta ki n g part i n t he 
st u d y will be watc he d caref ull y f or a n y si de effects, a n d tr yi n g t o pre ve nt t he m, w he n p ossi ble, is 
a n i m p orta nt part of all ca ncer care.
Ris ks rel ate d t o ri b ocicli b
Ri b ocicli b is a n i n vesti gati o nal dr u g a n d n ot all of t he si de effects are k n o w n. Seri o us si de 
effects, i ncl u di n g deat h, are a p ossi bilit y. T he l o n g-ter m effects of ri b ocicli b are als o u n k n o w n. 
Ris ks are p ossi ble si de effects of st u d y me dici ne gi ve n al o ne or i n c o m bi nati o n wit h ot her 
me dicati o n(s), a n d t h ose of ta ki n g bl o o d. Base d o n t he data fr o m o n g oi n g st u dies i n ca ncer 
patie nts, t he f oll o wi n g are t he p ossi ble ris ks wit h ta ki n g ri b ocicli b.
Ver y c o m m o n si de effects (m ay affect m ore t h a n 1 0 % of pe o ple )

L o w w hite bl o o d cell c o u nt w hic h i ncreases t he ris k of i nfecti o ns ( ne utr o pe nia or
le u k o pe nia)

I nfecti o ns (i ncl u di n g uri nar y tract i nfecti o ns, res pirat or y i nfecti o ns, gastr oe nteritis a n d
se vere, p ote ntiall y life-t hreate ni n g i nfecti o ns [se psis; t his is u nc o m m o n])

L o w re d bl o o d cell c o u nt w hic h ca n lea d t o tire d ness a n d wea k ness (a ne mia)


P h as e 1 b C o ns e nt
P a g e 1 1 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Na usea

Diarr hea

V o miti n g

C o nsti pati o n

M o ut h s ores, or pai n, i nfla m mati o n a n d/ or i nfecti o n of t he m o ut h

A b d o mi nal pai n

Tire d ness or ge neralize d wea k ness (fati g ue or ast he nia)

S welli n g of t he ar ms or le gs ( peri p heral oe de ma)

Fe ver ( p yre xia)

I ncrease i n t he bl o o d le vels of li ver para meters as i n dicate d b y li ver tests (s uc h as
tra nsa mi nases a n d/ or bilir u bi n)

Decrease d a p petite

Bac k pai n

Hea dac he

Dizzi ness

S h ort ness of breat h ( d ys p nea)

C o u g h

Hair t hi n ni n g or l oss (al o pecia)

S ki n ras h

Itc hi n g of t he s ki n ( pr urit us)
C o m m o n si de effects (m ay affect u p t o 1 0 % of pe o ple )

L o w platelet c o u nt w hic h ca n lea d t o eas y br uisi n g a n d blee di n g (t hr o m b oc yt o pe nia)

L o w w hite bl o o d cell c o u nt wit h fe ver (fe brile ne utr o pe nia)

L o w l y m p h oc yte c o u nt i n t he bl o o d t hat ca n pre dis p ose t o i nfecti o ns (l y m p h o pe nia)

Fai nti n g e pis o des/tra nsie nt l oss of c o nsci o us ness a n d p ost ural p ost ure (s y nc o pe)

E xcessi ve teari n g of t he e ye (i ncrease d lacri mati o n)

Dr y e ye

Taste alterati o n ( d ys ge usia)

Dr y m o ut h

S ore t hr oat ( or o p har y n geal pai n)

I n di gesti o n heart b ur n ( d ys pe psia)

Li ver t o xicit y ( he pat ot o xicit y: i nj ur y of t he li ver d ue t o li ver cell da ma ge, i ncl u di n g li ver
fail ure [t he latter is u nc o m m o n])

I ncrease i n creati ni ne (a waste pr o d uct i n t he bl o o d) a n d a decrease i n t he ki d ne y’s a bilit y
t o ha n dle t he b o d y’s waste ( bl o o d creati ni ne i ncrease d)

C ha n ges i n t he electrical acti vit y of t he heart calle d Q Tc pr ol o n gati o n. T his is a n
a b n or malit y of t he heart r h yt h m a n d ma y ca use dizzi ness, pal pitati o ns, fai nti n g, a n d i n
se vere cases l oss of c o nsci o us ness a n d e ve n deat h

Decrease d bl o o d calci u m le vels ( h y p ocalcae mia)

Decrease d bl o o d p otassi u m le vels ( h y p o kale mia)


P h as e 1 b C o ns e nt
P a g e 1 2 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

Decrease d bl o o d p h os p h or us le vels ( h y p o p h os p hate mia)

Re d ness of t he s ki n or re d de ni n g of t he s ki n (er yt he ma)

Dr y s ki n

L oss of s ki n c ol orati o n/ w hite ni n g, us uall y i n patc hes ( vitili g o)

Se nsati o n of l osi n g bala nce ( verti g o)
Rare b ut I m p orta nt ( m ay affect less t h a n 5 % of pe o ple ):

P ote ntial acc u m ulati o n of ri b ocicli b i n t he t h yr oi d gla n d. I n rats, ri b ocicli b was f o u n d t o
acc u m ulate i n t he t h yr oi d gla n d, b ut t here was n o e vi de nce of da ma ge t o t he t h yr oi d
gla n d. T here ha ve bee n n o re p orts of a b n or mal t h yr oi d f u ncti o n i n a n y patie nt s o far.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d M E K 1 6 2 die d fr o m blee di n g i n t he
brai n, w hic h was c o nsi dere d relate d t o ri b ocicli b a n d M E K 1 6 2 b y t he treati n g p h ysicia n.

O ne patie nt partici pati n g i n a trial was dia g n ose d wit h ac ute l y m p h o blastic le u ke mia
( A L L), w hic h t he treati n g p h ysicia n c o nsi dere d p ossi bl y relate d t o ri b ocicli b.

O ne patie nt partici pati n g i n a trial was dia g n ose d wit h ac ute res pirat or y fail ure, w hic h
was c o nsi dere d p ossi bl y relate d t o ri b ocicli b

F o ur partici pa nt deat hs occ urre d o n a breast ca ncer st u d y, w hic h were c o nsi dere d t o be
relate d t o ri b ocicli b. T w o deat hs were d ue t o ac ute res pirat or y fail ure, a n d t he ot her 
ca uses of deat h were p ne u m o nia a n d s u d de n deat h.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole was dia g n ose d wit h
m yel o d ys plastic s y n dr o me, w hic h was c o nsi dere d p ossi bl y relate d t o ri b ocicli b. 
M yel o d ys plastic s y n dr o me ha p pe ns w he n t he b o ne marr o w, t he material i nsi de y o ur 
b o nes w here y o ur bl o o d cells are ma de, n o l o n ger w or ks n or mall y, w hic h ca n lea d t o 
feeli n g tire d, s h ort of breat h or ha vi n g s mall re d s p ots u n der y o ur s ki n ca use d b y blee di n g 
or i nfecti o ns.  

O n patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole e x perie nce d decrease d
s o di u m le vels. Y o u ma y feel tire d, ha ve a hea dac he, feel na usea or v o mit, or ha ve
cra m ps.

O ne patie nt partici pati n g i n a trial wit h ri b ocicli b a n d letr oz ole was dia g n ose d wit h heart
fail ure. Y o u mi g ht feel s h ort of breat h, wea k ness, s welli n g i n y o ur le gs, a n kles or feet, or
a n irre g ular or ra pi d heart beat.
Ris ks a n d si de effects relate d t o d ocet a xel a n d pre d nis o ne i ncl u de t h ose liste d bel o w: 
Li kel y

Ras h

Hair l oss

Fl ui d rete nti o n/s welli n g

Fati g ue

U pset st o mac h

S ore ness a n d/ or wea k ness of m uscles a n d/ or j oi nts


P h as e 1 b C o ns e nt
P a g e 1 3 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D

I ncrease d bl o o d s u gar le vels, w hic h ma y ca use i ncrease d t hirst, uri nati o n, a n d fati g ue

L o were d w hite bl o o d cell c o u nt t hat ma y lea d t o i ncrease d ris k of i nfecti o n

L o were d platelet c o u nt t hat ma y lea d t o i ncrease d br uisi n g or blee di n g

L o were d re d bl o o d cell c o u nt t hat ma y ca use tire d ness or s h ort ness of breat h (if t he c o u nt
gets t o o l o w y o u ma y nee d a tra nsf usi o n)
Less Li kel y

Diarr hea

Na usea a n d v o miti n g

M o ut h a n d t hr oat s ores

L oss of a p petite

L oss of refle xes

Dar ke ni n g or li g hte ni n g of fi n ger nail be ds

Peeli n g s ki n o n ha n ds a n d feet

I ns o m nia

N u m b ness a n d/ or ti n gli n g of t he fi n gers a n d t oes
Rare, b ut seri o us

St o mac h ulcers a n d/ or blee di n g

Se vere aller gic reacti o n (life-t hreate ni n g breat hi n g pr o ble ms)

A b n or mal f u ncti o n of t he a dre nal gla n d w hic h ca n ca use wea k ness a n d fati g ue, l o w bl o o d
press ure, na usea, v o miti n g, diarr hea, irrita bilit y a n d/ or restless ness, l oss of b o ne de nsit y

L o w bl o o d press ure

A b n or mal c ha n ges i n pers o nalit y
I n a d diti o n, y o u s h o ul d ne ver st o p t he pre d nis o ne s u d de nl y. If y o u nee d t o st o p t he pre d nis o ne, 
y o ur d oct or will a d vise y o u o n h o w t o sl o wl y st o p t he dr u g (calle d a “ta per”). If y o u were t o st o p 
ta ki n g pre d nis o ne s u d de nl y, y o u c o ul d bec o me ver y wea k a n d tire d, de vel o p ver y l o w bl o o d 
press ure, ver y l o w bl o o d s u gar, a n d a b n or malities of t he mi nerals i n y o ur bl o o dstrea m. W hile 
us uall y n ot se vere, if n ot treate d, t hese a b n or malities are p ote ntiall y fatal. If y o u ha ve a seri o us 
ill ness, i nfecti o n, or tra u ma, it will be necessar y t o i ncrease y o ur d ose of pre d nis o ne. A n yti me 
y o u see a d oct or f or a n y reas o n, y o u s h o ul d tell hi m/ her t hat y o u are ta ki n g pre d nis o ne.
We d o n ot k n o w t he si de effects of ri b ocicli b, d oceta xel, a n d pre d nis o ne w he n gi ve n al o ne or i n 
c o m bi nati o n wit h ot her dr u gs. A c o m bi nati o n of dr u gs mi g ht res ult i n seri o us or e ve n life-
t hreate ni n g si de effects. S o me o ver-t he-c o u nter a n d prescri pti o n me dicati o ns ca n re d uce t he 
effecti ve ness or i ncrease t he si de effects of t he st u d y treat me nts. Li ke wise, t he st u d y treat me nts 
ca n i ncrease t he si de effects or lesse n t he effecti ve ness of s o me me dicati o ns. T his mi g ht res ult i n 
seri o us or e ve n life-t hreate ni n g si de effects. Y o u s h o ul d al wa ys disc uss t he use of a n y dr u gs 
( o ver-t he-c o u nter dr u gs, prescri pti o n, or ille gal dr u gs or healt h f o o d s u p ple me nts) wit h y o ur 
d oct or w hile y o u are partici pati n g i n t his st u d y. T he st u d y pr ot oc ol descri bes w hic h me dici nes 
are pr o hi bite d d uri n g t he st u d y, a n d w hic h o nes ca n be ta ke n wit h ca uti o n.


P h as e 1 b C o ns e nt
P a g e 1 4 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
T here c o ul d be a d diti o nal u ne x pecte d si de effects w he n ri b ocicli b is ta ke n i n c o m bi nati o n wit h 
d oceta xel a n d pre d nis o ne.
Ris ks rel ate d t o Ne u p o ge n ( G- C S F):
G- C S F ca uses b o ne pai n i n ma n y pe o ple. T his pai n ma y occ ur i m me diatel y or se veral da ys after
recei vi n g G- C S F. T he pai n ma y feel li ke a n ac hi n g se nsati o n i n t he b o nes of t he bac k, hi ps,
pel vis, or breast b o ne. Pai n relie vers, s uc h as aceta mi n o p he n ( T yle n ol ®) or i b u pr ofe n ( A d vil ®,
N u pri n ®) ma y be use d t o lesse n t his disc o mf ort.
Occasi o nall y, G- C S F ma y ca use fl u-li ke s y m pt o ms. If y o u alrea d y ha ve i nfla m mati o n of certai n 
bl o o d vessels, art hritis, ecze ma or ps oriasis, G- C S F ma y ca use t hese c o n diti o ns t o get w orse. 
Ot her occasi o nal si de effects i ncl u de hea dac hes, m uscle ac hes, tire d ness, na usea a n d v o miti n g, 
a n d tr o u ble slee pi n g. T hese s y m pt o ms us uall y g o a wa y wit hi n 2 or 3 da ys after st o p pi n g G- C S F.
T he f oll o wi n g si de effects are rare a n d are n ot ge nerall y seri o us pr o ble ms:

B ur ni n g, s welli n g, a n d re d ness at t he i njecti o n site

Aller gic reacti o ns ( hi ves/s ki n ras h, itc hi n g, w heezi n g, fe ver, ra pi d heart rate, s h ort ness of
breat h, dizzi ness)

L o weri n g of bl o o d press ure

C ha n ges i n bl o o d c he mistr y le vels

E nlar ge me nt of t he s plee n (see n i n s o me patie nts treate d wit h G- C S F f or a n e xte n de d
peri o d of ti me)
Rare b ut seri o us:

Se vere reacti o ns t o G- C S F i n patie nts wit h sic kle cell a ne mia a n d relate d sic kle cell
diseases.

Pai n a n d blee di n g fr o m t he s plee n, w hic h ma y re q uire s ur ger y. If y o u feel pai n i n y o ur
u p per left si de j ust bel o w t he ri b ca ge, c o ntact y o ur d oct or i m me diatel y.
Ot her ris ks rel ate d t o t his st u d y i ncl u de:
Bl o o d dr a wi n g ( ve ni p u nct ure) ris ks: Dra wi n g bl o o d ma y ca use te m p orar y disc o mf ort fr o m t he 
nee dle stic k, br uisi n g, a n d i nfecti o n. I n rare i nsta nces w here a n urse, a d oct or, or a la b orat or y 
tec h nicia n s ustai ns a n e x p os ure t o y o ur bl o o d, tiss ue or b o d y fl ui ds b y nee dle stic k, c ut or s plas h 
t o m uc osa or da ma ge d s ki n, it ma y be necessar y t o test y o ur bl o o d, tiss ue, or b o d y fl ui d sa m ple 
f or certai n viral i nfecti o ns i ncl u di n g He patitis B a n d C a n d HI V o n t he sa m ple alrea d y a vaila ble. 
T his is t o e na ble t hat pers o n t o recei ve a p pr o priate c o u nseli n g, m o nit ori n g, a n d treat me nt if 
necessar y. I n t his i nsta nce, t he St u d y D oct or will offer y o u t he i nf or mati o n rele va nt t o y o ur 
healt h a n d a d vise y o u o n t he ne xt ste ps. C o nfi de ntialit y of y o ur data will be res pecte d at all 
ti mes.


P h as e 1 b C o ns e nt
P a g e 1 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
C T sc a n ris ks: C T sca ns i n v ol ve t he ris ks of ra diati o n. I n a d diti o n, if c o ntrast material (i o di ne 
d ye) is use d, t here is a sli g ht ris k of de vel o pi n g a n aller gic reacti o n. T he aller gic reacti o n ca n be 
mil d (itc hi n g, ras h) t o se vere ( diffic ult y breat hi n g, s h oc k, or rarel y, deat h). T he c o ntrast material 
ma y als o ca use ki d ne y pr o ble ms, es peciall y if y o u are de h y drate d or ha ve p o or ki d ne y f u ncti o n. 
T he st u d y d oct ors will as k y o u a b o ut a n y aller gies or relate d c o n diti o ns y o u ma y ha ve bef ore t he 
pr oce d ure is d o ne. If y o u ha ve a n y of t hese aller gies or c o n diti o ns, y o u ma y n ot be all o we d t o 
ha ve a C T sca n i n t he st u d y.
Ha vi n g a C T sca n ma y mea n s o me a d de d disc o mf ort f or y o u. I n partic ular, y o u ma y be b ot here d 
b y feeli n gs of cla ustr o p h o bia w he n place d i nsi de t he C T sca n ner, or b y l yi n g i n a still p ositi o n 
f or a l o n g ti me. If c o ntrast material is use d, y o u ma y feel disc o mf ort w he n it is i njecte d i nt o y o ur 
b o d y. Y o u ma y feel war m a n d fl us he d a n d/ or get a metallic taste i n y o ur m o ut h. Rarel y, t he 
c o ntrast material ma y ca use na usea, v o miti n g or a hea dac he.
M RI ris ks : Beca use t he M RI mac hi ne acts li ke a lar ge ma g net, it c o ul d m o ve ir o n-c o ntai ni n g 
o bjects i n t he M RI r o o m d uri n g y o ur e xa mi nati o n, w hic h i n t he pr ocess c o ul d p ossi bl y har m 
y o u. Preca uti o ns ha ve bee n ta ke n t o pre ve nt s uc h a n e ve nt fr o m ha p pe ni n g; l o ose metal o bjects, 
li ke p oc ket k ni ves or ke y c hai ns, are n ot all o we d i n t he M RI r o o m. If y o u ha ve a piece of metal 
i n y o ur b o d y, s uc h as a fra g me nt i n y o ur e ye, a ne ur ys m cli ps, ear i m pla nts, s pi nal ner ve 
sti m ulat ors, or a pace ma ker, y o u will n ot be all o we d i nt o t he M RI r o o m a n d ca n n ot ha ve a n 
M RI.
Ha vi n g a n M RI ma y mea n s o me a d de d disc o mf ort f or y o u. I n partic ular, y o u ma y be b ot here d b y 
feeli n gs of cla ustr o p h o bia a n d b y t he l o u d ba n gi n g n oise d uri n g t he st u d y. Te m p orar y heari n g 
l oss has bee n re p orte d fr o m t his l o u d n oise. T his is w h y y o u will be as ke d t o wear ear pl u gs. At 
ti mes d uri n g t he test, y o u ma y be as ke d t o n ot s wall o w f or a w hile, w hic h ca n feel 
u nc o mf orta ble.
C o ntr ast a ge nt ( g a d oli ni u m) ris ks : A fe w si de effects of ga d oli ni u m i njecti o n s uc h as 
mil d hea dac he, na usea, a n d l ocal pai n ma y occ ur. Rarel y, (less t ha n 1 % of t he ti me) l o w 
bl o o d press ure a n d li g ht hea de d ness ma y occ ur. T his ca n be treate d i m me diatel y wit h 
fl ui ds gi ve n t hr o u g h o ne of y o ur vei ns. Ver y rarel y, (less t ha n o ne i n o ne t h o usa n d), 
patie nts are aller gic t o ga d oli ni u m. T hese aller gic effects m ost c o m m o nl y i ncl u de hi ves 
a n d itc h y e yes, b ut m ore se vere reacti o ns, i ncl u di n g s h ort ness of breat h, ha ve bee n see n.
Patie nts wit h se vere ki d ne y disease s o meti mes ha ve a ba d reacti o n t o t he ga d oli ni u m 
c o ntrast material. T his c o n diti o n is calle d ne p hr o ge nic s yste mic fi br osis ( N S F). It ca n 
ca use s ki n t o ti g hte n  or scar a n d ca n da ma ge i nter nal or ga ns. S o meti mes it ca n be life-
t hreate ni n g. T here are n o re p orts of N S F i n patie nts wit h n or mal ki d ne y f u ncti o n.
Bef ore y o u ha ve a n M RI sca n re q uiri n g a n i njecti o n of ga d oli ni u m c o ntrast, y o u will 
nee d t o ha ve a bl o o d test i n or der t o c hec k t he f u ncti o n of y o ur ki d ne ys. Base d o n y o ur 
me dical hist or y a n d t he res ults of t his test, a d oct or will deci de w het her it is safe f or y o u 
t o u n der g o t he M RI sca ns.


P h as e 1 b C o ns e nt
P a g e 1 6 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
B o ne sc a n ris k : A b o ne sca n i n v ol ves e x p os ure t o ra diati o n. ( See Ra diati o n Ris ks bel o w). S o me 
pe o ple ma y ha ve a cl ose d-i n feeli n g w hile u n der t he ca mera. As i n a n y i njecti o n, y o u ma y ha ve 
s welli n g or br uisi n g at t he i njecti o n site.
R a di ati o n ris ks: T his researc h st u d y i n v ol ves e x p os ure t o ra diati o n. N ot all t his ra diati o n 
e x p os ure is necessar y f or y o ur me dical care a n d is f or researc h p ur p oses o nl y. T his a m o u nt of 
ra diati o n ma y i n v ol ve a l o w ris k of ca ncer. H o we ver, we belie ve t hat t his ris k, gi ve n y o ur o verall 
me dical c o n diti o n is n ot cli nicall y rele va nt. If y o u ha ve a n y q uesti o ns re gar di n g t he use of 
ra diati o n or t he ris ks i n v ol ve d, please c o ns ult t he p h ysicia n c o n d ucti n g t he st u d y.
Electr oc ar di o gr a m ( E K G/ E C G) ris ks: T he E C G i n v ol ves placi n g electr o des o n t he s ki n. Y o u 
ma y e x perie nce a n aller gic reacti o n t o t he a d hesi ve use d t o attac h t he electr o des t o t he s ki n. 
T hese s y m pt o ms are ge nerall y mil d a n d clear u p o n t heir o w n. Please let y o ur d oct or k n o w if y o u 
are a ware of a n y aller gies.
Ec h oc ar di o gr a m ( E C H O): T he car diac ec h o gra m mi g ht ca use y o u t o be u nc o mf orta ble fr o m 
t he press ure of t he pr o be o n y o ur c hest or l yi n g still f or t he e xa mi nati o n.
M U G A sc a n ris ks : M U G A sca ns i n v ol ve t he ris ks of ra diati o n ( See Ra diati o n Ris ks a b o ve). 
Y o u ma y de vel o p br uisi n g w here t he nee dle is place d i n y o ur vei ns t o a d mi nister t he ra di oacti ve 
s u bsta nce. Y o u ma y be u nc o mf orta ble l yi n g flat.
S afe H a n dli n g of Me dic ati o ns: Ha n dli n g ri b ocicli b a n d ha vi n g c o ntact wit h a n y uri ne, feces, or 
v o mit fr o m patie nts recei vi n g ri b ocicli b ma y p ose s o me ris k t o y o u a n d y o ur care gi vers. T o 
a v oi d e x p os ure t o ri b ocicli b a n d a n y ass ociate d ris ks, y o u a n d y o ur fa mil y me m bers/care gi vers 
will be e d ucate d b y a me m ber of t he st u d y tea m o n h o w t o safel y ha n dle, pr o perl y dis p ose of, 
a n d clea n pr o d ucts t hat ma y be c o nta mi nate d wit h ri b ocicli b.
D ose Esc al ati o n Ris ks: Si nce patie nts will be assi g ne d t o differe nt d oses of st u d y dr u g, s o me 
patie nts ma y recei ve a d ose of t he dr u g t hat is t o o s mall t o be effecti ve w hile ot hers ma y recei ve 
a hi g her d ose t hat ma y ca use i ncrease d si de effects. Y o u ca n as k y o ur st u d y d oct or w hat d ose 
y o u will be gi ve n.
Re pr o d ucti ve Ris ks: Y o u s h o ul d n ot fat her a ba b y w hile o n t his st u d y beca use t he dr u gs i n t his 
st u d y ca n affect a n u n b or n ba b y. It is i m p orta nt t o u n dersta n d t hat y o u nee d t o use birt h c o ntr ol 
w hile o n t his st u d y. Y o u m ust al wa ys wear a c o n d o m d uri n g i nterc o urse (e ve n if y o u ha ve ha d a 
vasect o m y), a n d if fertile y o u m ust als o use s per mici de. Y o u m ust c o nti n ue t o wear a c o n d o m 
w hile ta ki n g t he dr u g a n d f or 3 0 da ys after st o p pi n g treat me nt. F or m ore i nf or mati o n re gar di n g 
c o ntrace pti o n please s pea k t o y o ur st u d y d oct or.
U n k n o w n Ris ks: T he e x peri me ntal treat me nts ma y ha ve si de effects t hat n o o ne k n o ws a b o ut. 
T he researc hers will let y o u k n o w if t he y lear n a n yt hi n g t hat mi g ht ma ke y o u c ha n ge y o ur mi n d 
a b o ut partici pati n g i n t he st u d y.
F or m ore i nf or mati o n a b o ut ris ks a n d si de effects, as k y o ur st u d y d oct or.


P h as e 1 b C o ns e nt
P a g e 1 7 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
Are t here be nefits t o t a ki n g p art i n t he st u d y ?
Ta ki n g part i n t his st u d y ma y or ma y n ot ma ke y o ur healt h better. W hile d oct ors h o pe t hat t he 
c o m bi nati o n of ri b ocicli b wit h d oceta xel pl us pre d nis o ne will be m ore usef ul a gai nst ca ncer 
c o m pare d t o t he us ual treat me nt, t here is n o pr o of of t his. Y o ur c o n diti o n ma y e ve n get w orse 
d uri n g t he st u d y. We d o k n o w t hat t he i nf or mati o n fr o m t his st u d y will hel p d oct ors lear n m ore 
a b o ut t heses st u d y dr u g c o m bi nati o ns as a treat me nt f or ca ncer. T his i nf or mati o n c o ul d hel p 
f ut ure ca ncer patie nts. H o we ver, t here is n o g uara ntee t hat t his will ha p pe n.
W h at ot her c h oices d o I h a ve if I d o n ot t a ke p art i n t his st u d y ?
Y o ur ot her c h oices ma y i ncl u de:

Getti n g treat me nt or care f or y o ur ca ncer wit h o ut bei n g i n a st u d y.

Ta ki n g part i n a n ot her st u d y.

Getti n g n o treat me nt.

Getti n g c o mf ort care als o calle d palliati ve care. T his t y pe of care hel ps re d uce pai n,
tire d ness, a p petite pr o ble ms a n d ot her pr o ble ms ca use d b y t he ca ncer. It d oes n ot treat t he
ca ncer directl y b ut i nstea d tries t o i m pr o ve h o w y o u feel. C o mf ort care tries t o kee p y o u
as acti ve a n d c o mf orta ble as p ossi ble.
Please tal k t o y o ur d oct or a b o ut y o ur c h oices bef ore deci di n g if y o u will ta ke part i n t his st u d y.
Will m y me dic al i nf or m ati o n be ke pt pri v ate ?
We will d o o ur best t o ma ke s ure t hat t he pers o nal i nf or mati o n i n y o ur me dical rec or d is ke pt 
pri vate. H o we ver, we ca n n ot g uara ntee t otal pri vac y. Y o ur pers o nal i nf or mati o n ma y be gi ve n 
o ut if re q uire d b y la w. If i nf or mati o n fr o m t his st u d y is p u blis he d or prese nte d at scie ntific 
meeti n gs, y o ur na me a n d ot her pers o nal i nf or mati o n will n ot be use d.
Or ga nizati o ns t hat ma y l o o k at a n d/ or c o p y y o ur me dical rec or ds f or researc h, q ualit y ass ura nce, 
a n d data a nal ysis i ncl u de:

N o vartis (t he dr u g s u p plier) a n d its a ut h orize d a ge nts

Pr ostate Ca ncer F o u n dati o n

T he U ni versit y of Calif or nia

T he Nati o nal Ca ncer I nstit ute ( N CI) a n d ot her g o ver n me nt a ge ncies, e. g., t he F o o d a n d
Dr u g A d mi nistrati o n ( F D A), i n v ol ve d i n kee pi n g researc h safe f or pe o ple. G o ver n me ntal
a ge ncies i n ot her c o u ntries w here t he st u d y dr u g ma y be c o nsi dere d f or a p pr o val.
Partici pati o n i n researc h ma y i n v ol ve a l oss of pri vac y, b ut i nf or mati o n a b o ut y o u will be 
ha n dle d as c o nfi de ntiall y as p ossi ble. A me dical rec or d will be create d beca use of y o ur 
partici pati o n i n t his st u d y. Y o ur c o nse nt f or m a n d s o me of y o ur researc h test res ults will be 


P h as e 1 b C o ns e nt
P a g e 1 8 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
i ncl u de d i n t his rec or d. T heref ore, y o ur ot her d oct ors ma y bec o me a ware of y o ur partici pati o n. 
H os pital re g ulati o ns re q uire t hat all healt h care pr o vi ders treat i nf or mati o n i n me dical rec or ds 
c o nfi de ntiall y.
W h at are t he c osts of t a ki n g p art i n t his st u d y ?
St u d y dr u g (ri b ocicli b) will be pr o vi de d b y N o vartis a n d will n ot c ost y o u a n y m o ne y. Y o u 
a n d/ or y o ur healt h pla n/i ns ura nce c o m pa n y will nee d t o pa y f or d oceta xel a n d pre d nis o ne.
T w o t y pes of pr oce d ures will be d o ne d uri n g t his st u d y. S o me are part of y o ur sta n dar d me dical 
care a n d ot hers are o nl y f or researc h. Y o u or y o ur i ns urer will be bille d f or t he sta n dar d me dical 
care. Y o u will be res p o nsi ble f or y o ur c o- pa ys, de d ucti bles, a n d a n y ot her c har ges t hat y o ur 
i ns urer will n ot pa y. T here is a p ossi bilit y t hat y o ur i ns urer ma y n ot c o ver all sta n dar d me dical 
care c osts if y o u are recei vi n g me dical ser vices o ut of net w or k. A n y pr oce d ures d o ne o nl y f or 
researc h will n ot be c har ge d t o y o u or y o ur i ns urer.
Will I be p ai d f or t a ki n g p art i n t his st u d y ?
Y o u will n ot be pai d f or ta ki n g part i n t his st u d y.
W h at h a p pe ns if I a m i nj ure d bec a use I t o o k p art i n t his st u d y ?
It is i m p orta nt t hat y o u tell y o ur st u d y d oct or, Ra h ul A g gar wal, M. D., if y o u feel t hat y o u ha ve 
bee n i nj ure d beca use of ta ki n g part i n t his st u d y. Y o u ca n tell t he d oct or i n pers o n or call  
 
.
Tre at me nt a n d C o m pe ns ati o n f or I nj ur y: If y o u are i nj ure d as a res ult of bei n g i n t his 
st u d y, t he U ni versit y of Calif or nia will pr o vi de necessar y me dical treat me nt. T he c osts of 
t he treat me nt ma y be bille d t o y o u or y o ur i ns urer j ust li ke a n y ot her me dical c osts, or 
c o vere d b y t he U ni versit y of Calif or nia, de pe n di n g o n a n u m ber of fact ors. T he 
U ni versit y a n d t he st u d y s p o ns or d o n ot n or mall y pr o vi de a n y ot her f or m of
c o m pe nsati o n f or i nj ur y. F or f urt her i nf or mati o n a b o ut t his, y o u ma y call t he office of t he 
C o m mittee o n H u ma n Researc h at 4 1 5- 4 7 6- 1 8 1 4.
W h at are m y ri g hts if I t a ke p art i n t his st u d y ?
Ta ki n g part i n t his st u d y is y o ur c h oice. Y o u ma y c h o ose eit her t o ta ke part or n ot t o ta ke part i n 
t he st u d y. If y o u deci de t o ta ke part i n t his st u d y, y o u ma y lea ve t he st u d y at a n y ti me. N o matter 
w hat decisi o n y o u ma ke, t here will be n o pe nalt y t o y o u a n d y o u will n ot l ose a n y of y o ur re g ular 
be nefits. Lea vi n g t he st u d y will n ot affect y o ur me dical care. Y o u ca n still get y o ur me dical care 
fr o m o ur i nstit uti o n.


P h as e 1 b C o ns e nt
P a g e 1 9 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
We will tell y o u a b o ut ne w i nf or mati o n or c ha n ges i n t he st u d y t hat ma y affect y o ur healt h or 
y o ur willi n g ness t o c o nti n ue i n t he st u d y.
I n t he case of i nj ur y res ulti n g fr o m t his st u d y, y o u d o n ot l ose a n y of y o ur le gal ri g hts t o see k 
pa y me nt b y si g ni n g t his f or m.
W h o c a n a ns wer m y q uesti o ns a b o ut t he st u d y ?
Y o u ca n tal k t o y o ur st u d y d oct or a b o ut a n y q uesti o ns, c o ncer ns, or c o m plai nts y o u ha ve a b o ut 
t his st u d y. C o ntact y o ur st u d y d oct or Ra h ul A g gar wal, M. D. 
.
If y o u wis h t o as k q uesti o ns a b o ut t he st u d y or y o ur ri g hts as a researc h partici pa nt t o s o me o ne 
ot her t ha n t he researc hers or if y o u wis h t o v oice a n y pr o ble ms or c o ncer ns y o u ma y ha ve a b o ut 
t he st u d y, please call t he Office of t he C o m mittee o n H u ma n Researc h at 4 1 5- 4 7 6- 1 8 1 4.
A descri pti o n of t his cli nical trial will be a vaila ble o n htt p:// w w w. Cli nical Trials. g o v, as re q uire d 
b y U S La w. T his We b site will n ot i ncl u de i nf or mati o n t hat ca n i de ntif y y o u. At m ost, t he We b 
site will i ncl u de a s u m mar y of t he res ults. Y o u ca n searc h t his We b site at a n y ti me.
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
O P TI O N A L
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
Ple ase n ote: T his secti o n of t he i nf or me d c o nse nt f or m is a b o ut a d diti o n al rese arc h st u dies 
t h at are bei n g d o ne.
Y o u c a n s a y " yes " or " n o " t o e ac h of t he f oll o wi n g st u dies. Ple ase m ar k y o ur c h oice f or 
e ac h st u d y.
Bi o m ar ker St u d y: ( o pti o nal f or P hase I b d ose escalati o n patie nts)

W hat: Bi o mar kers are i m p orta nt bi ol o gical i n dicat ors, w hic h ca n be meas ure d fr o m bl o o d
sa m ples.

W he n: Bi o mar ker sa m ples ma y be c ollecte d bef ore y o u start y o ur st u d y treat me nt

W h y: S o t hat t he researc hers ca n lear n m ore a b o ut y o ur ca ncer


P h as e 1 b C o ns e nt
P a g e 2 0 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
A b o ut Usi n g S a m ples f or Rese arc h
S u bjects ta ki n g part i n t his cli nical st u d y are bei n g i n vite d t o ta ke part i n t his o pti o nal researc h 
st u d y. T his st u d y will use a n y re mai ni n g bl o o d sa m ples f or a d diti o nal researc h relate d t o t he 
ri b ocicli b, d oceta xel, pre d nis o ne, a n d/ or ca ncer.
A n y data ge nerate d fr o m t he a d diti o nal researc h st u dies will bel o n g t o U C S F a n d will n ot 
bec o me part of y o ur me dical rec or d.
Y o u ca n c h o ose n ot t o ha ve y o ur sa m ples st ore d f or a d diti o nal use a n d still be a part of t he st u d y.
Ge netic i nf or mati o n (als o k n o w n as ge n ot y pe data) a n d t he me dical rec or d data (als o k n o w n as 
p he n ot y pe data) ma y be s hare d br oa dl y i n a c o de d f or m f or f ut ure ge netic researc h or a nal ysis. 
We ma y gi ve certai n me dical i nf or mati o n a b o ut y o u (f or e xa m ple, dia g n osis, bl o o d press ure, a ge 
if less t ha n 8 5) t o ot her scie ntists or c o m pa nies n ot at U C S F, i ncl u di n g t o a ( p u blic or c o ntr olle d 
access) g o ver n me nt healt h researc h data base, b ut we will n ot gi ve t he m y o ur na me, a d dress, 
p h o ne n u m ber, or a n y ot her i de ntifia ble i nf or mati o n. Researc h res ults fr o m t hese st u dies will n ot 
be ret ur ne d t o y o u ( descri be a n y rare i nsta nces t hat t his ma y occ ur).
D o nati n g data ma y i n v ol ve a l oss of pri vac y, b ut i nf or mati o n a b o ut y o u will be ha n dle d as 
c o nfi de ntiall y as p ossi ble. St u d y data will be p h ysicall y a n d electr o nicall y sec ure d. As wit h a n y 
use of electr o nic mea ns t o st ore data, t here is a ris k of breac h of data sec urit y. Ge netic 
i nf or mati o n t hat res ults fr o m t his st u d y d oes n ot ha ve me dical or treat me nt i m p orta nce at t his 
ti me. H o we ver, t here is a ris k t hat i nf or mati o n a b o ut ta ki n g part i n a ge netic st u d y ma y i nfl ue nce 
i ns ura nce c o m pa nies a n d/ or e m pl o yers re gar di n g y o ur healt h. Ta ki n g part i n a ge netic st u d y ma y 
als o ha ve a ne gati ve i m pact or u ni nte n de d c o nse q ue nces o n fa mil y or ot her relati o ns hi ps. It is 
p ossi ble t hat f ut ure researc h c o ul d o ne da y hel p pe o ple of t he sa me race, et h nicit y, or se x as y o u. 
H o we ver, it is als o p ossi ble t hr o u g h t hese ki n ds of st u dies t hat ge netic traits mi g ht c o me t o be 
ass ociate d wit h y o ur gr o u p. I n s o me cases, t his c o ul d rei nf orce har mf ul stere ot y pes.
T here will be n o direct be nefit t o y o u fr o m all o wi n g y o ur data t o be ke pt a n d use d f or f ut ure 
researc h. H o we ver, we h o pe we will lear n s o met hi n g t hat will c o ntri b ute t o t he a d va nce me nt of 
scie nce a n d u n dersta n di n g of healt h a n d disease. If t he data or a n y ne w pr o d ucts, tests or 
disc o veries t hat res ult fr o m t his researc h ha ve p ote ntial c o m mercial val ue, y o u will n ot s hare i n 
a n y fi na ncial be nefits. If y o u deci de later t hat y o u d o n ot wa nt y o ur i nf or mati o n t o be use d f or 
f ut ure researc h, y o u ca n n otif y t he i n vesti gat or i n writi n g at 
Ra h ul A g gar wal, M D
U ni versit y of Calif or nia Sa n Fra ncisc o
a n d a n y re mai ni n g data will be destr o ye d. H o we ver, we ca n n ot retract a n y data has bee n s hare d 
wit h ot her researc hers.


P h as e 1 b C o ns e nt
P a g e 2 1 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
T hi n gs t o T hi n k A b o ut
T he c h oice t o all o w U C S F t o use t he left o ver bl o o d sa m ples f or f ut ure researc h is u p t o y o u. N o 
matter w hat y o u deci de t o d o, it will n ot affect y o ur care.
If y o u deci de n o w t hat y o ur bl o o d sa m ples ca n be ke pt f or researc h, y o u ca n c ha n ge y o ur mi n d at 
a n y ti me. J ust c o ntact us a n d let us k n o w t hat y o u d o n ot wa nt us t o use y o ur sa m ples. T he n a n y 
sa m ple t hat re mai ns will n o l o n ger be use d f or researc h.
I n t he f ut ure, pe o ple w h o d o researc h ma y nee d t o k n o w m ore a b o ut y o ur healt h.
W hile U C S F ma y gi ve t he m re p orts a b o ut y o ur healt h, it will n ot gi ve t he m y o ur na me, a d dress, 
p h o ne n u m ber, or a n y ot her i nf or mati o n t hat will let t he researc hers k n o w w h o y o u are.
Y o ur sa m ples will be use d o nl y f or researc h a n d will n ot be s ol d.
T he researc h d o ne wit h y o ur bl o o d sa m ples ma y hel p t o de vel o p ne w pr o d ucts i n t he f ut ure.
Be nefits
T he researc h t hat ma y be d o ne wit h y o ur bl o o d sa m ple is n ot desi g ne d s pecificall y t o hel p y o u. It 
mi g ht hel p pe o ple w h o ha ve ca ncer a n d ot her diseases i n t he f ut ure. T he be nefits of researc h 
usi n g bl o o d sa m ple i ncl u de lear ni n g m ore a b o ut w hat ca uses ca ncer a n d ot her diseases, h o w t o 
pre ve nt t he m, a n d h o w t o treat t he m.
U C S F will be t he e xcl usi ve o w ner of a n y data a n d disc o veries res ulti n g fr o m t his researc h.
A n y c o m mercial pr o d uct de vel o pe d at U C S F as a res ult of t hese st u dies w o ul d be fr o m t he 
a nal ysis of all sa m ples c ollecte d i n t his st u d y, n ot fr o m a n i n di vi d ual s u bject’s sa m ple.
O ver all Ris k
T here is s o me ris k fr o m a breac h of c o nfi de ntialit y. We will d o o ur best t o ma ke s ure t hat y o ur 
pers o nal i nf or mati o n will be ke pt pri vate.
T he c ha nce t hat t his i nf or mati o n will be gi ve n t o s o me o ne else is ver y s mall.
If t his i nf or mati o n were release d t o y o u, y o ur fa mil y, or t hir d parties, it c o ul d p ote ntiall y be 
mis use d. S uc h mis use c o ul d lea d t o a d verse ps yc h ol o gical effects or u n desire d effects o n t he 
a bilit y of y o u or y o ur fa mil y me m bers t o o btai n a j o b or i ns ura nce.
T he t y pes of me dical i nf or mati o n t hat c o ul d be c ollecte d are y o ur pre vi o us me dical hist or y, 
la b orat or y val ues, t y pe of ca ncer, a n d t u m or sta gi n g.


P h as e 1 b C o ns e nt
P a g e 2 2 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
I n or der t o mi ni mize t hese p ote ntial ris ks, all researc h i nf or mati o n o btai ne d f or y o ur bl o o d 
sa m ple a n d me dical rec or ds will be ke pt c o nfi de ntial as descri be d a b o ve.
M a ki n g Y o ur C h oice
Please rea d t he se nte nces bel o w a n d t hi n k a b o ut y o ur c h oice. After rea di n g t he se nte nce, please 
p ut y o ur i nitials i n t he " Yes" or " N o" b o x. If y o u ha ve a n y q uesti o ns, please tal k t o y o ur d oct or 
or n urse, or call o ur researc h re vie w b oar d at 4 1 5- 4 7 6- 1 8 1 4.
1. I a gree t o all o w U C S F t o st ore a n d use m y left o ver bl o o d a n d/ or t u m or s a m ples f or
a d diti o n al rese arc h tests rel ate d t o ri b ocicli b, d ocet a xel, pre d nis o ne a n d/ or c a ncer.
Y E S
N O


P h as e 1 b C o ns e nt
P a g e 2 3 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
C O N S E N T
Y o u ha ve bee n gi ve n c o pies of t his c o nse nt f or m a n d t he E x peri me ntal S u bject's Bill of Ri g hts t o 
kee p.
Y o u will be as ke d t o si g n a se parate f or m a ut h orizi n g access, use, creati o n, or discl os ure of 
healt h i nf or mati o n a b o ut y o u.
P A R TI CI P A TI O N I N R E S E A R C H I S V O L U N T A R Y. Y o u ha ve t he ri g ht t o decli ne t o 
partici pate or t o wit h dra w at a n y p oi nt i n t his st u d y wit h o ut pe nalt y or l oss of be nefits t o w hic h 
y o u are ot her wise e ntitle d.
If y o u wis h t o partici pate i n t his st u d y, y o u s h o ul d si g n bel o w.
Date
Partici pa nt's Si g nat ure f or C o nse nt
Date
Partici pa nt's Pri nte d Na me
Date
Pers o n O btai ni n g C o nse nt
Date
Wit ness – O nl y re q uire d if t he partici pa nt is a n o n- E n glis h s pea ker


P h as e 1 b C o ns e nt
P a g e 2 4 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
LI S T O F P R O HI BI T E D M E DI C A TI O N S
C at e g or y
Dr u g N a m e
Str o n g C Y P 3 A 4/ 5 
i n hi bit or s
At a z a n a vir/rit o n a vir, b o c e pr e vir, cl arit hr o m y ci n, c o bi ci st at, c o ni v a pt a n, 
d a n o pr e vir/rit o n a vir, d ar u n a vir/rit o n a vir, el vit e gr a vir/rit o n a vir, gr a p efr uit j ui c e, 
i d el ali si b, i n di n a vir, i n di n a vir/rit o n a vir, itr a c o n a z ol e, k et o c o n a z ol e, l o pi n a vir/rit o n a vir, 
mi b efr a dil, n ef a z o d o n e, n elfi n a vir, o m bit a s vir/ p arit a pr e vir/ d a s a b u vir/rit o n a vir 
( VI E KI R A P A K), p o s a c o n a z ol e, rit o n a vir, s a q ui n a vir/rit o n a vir, t el a pr e vir, 
t elit hr o m y ci n, ti pr a n a vir/rit o n a vir, tr ol e a n d o m y ci n v ori c o n a z ol e
Str o n g C Y P 3 A 4/ 5
i n d u c er s
c ar b a m a z e pi n e, e n z al ut a mi d e, l u m a c aft or, mit ot a n e, p h e n o b ar bit al, p h e n yt oi n, 
rif a b uti n, rif a m pi n (rif a m pi ci n), St. J o h n' s w ort ( h y p eri c u m p erf or at u m)
M e di c ati o n s wit h a
k n o w n ri s k f or Q T
pr ol o n g ati o n
A mi o d ar o n e, a n a gr eli d e, ar s e ni c tri o xi d e, a st e mi z ol e, a zit hr o m y ci n, c hl or o q ui n e, 
c hl or pr o m a zi n e, cil o st a z ol, ci pr ofl o x a ci n, ci s a pri d e, cit al o pr a m, cl arit hr o m y ci n, 
di s o p yr a mi d e, d of etili d e, d o m p eri d o n e, d o n e p e zil, dr o n e d ar o n e, dr o p eri d ol, 
er yt hr o m y ci n, e s cit al o pr a m, fl e c ai ni d e, fl u c o n a z ol e, g atifl o x a ci n e, gr e p afl o x a ci n, 
h al of a ntri n e, h al o p eri d ol, i b utili d e, l e v ofl o x a ci n, l e v o m e pr o m a zi n e, l e v o s ul piri d e, 
m et h a d o n e, m o xifl o x a ci n, o n d a n s etr o n, o x ali pl ati n, p a p a v eri n e H Cl (i ntr a- c or o n ar y), 
p e nt a mi di n e, pi m o zi d e, pr o c ai n a mi d e, pr o p of ol, q ui ni di n e, r o xit hr o m y ci n, 
s e v ofl ur a n e, s ot al ol, s ul piri d e, s ult o pri d e, t erli pr e s si n, t er o dili n e, t hi ori d a zi n e, 
v a n d et a ni b
C Y P 3 A 4/ 5 
s u b str at e s wit h N TI
Alf e nt a nil, a st e mi z ol e, ci s a pri d e, c y cl o s p ori n e, di er g ot a mi n e ( di h y dr o er g ot a mi n e), 
er g ot a mi n e, f e nt a n yl, pi m o zi d e, q ui ni di n e, sir oli m u s, t a cr oli m u s
Ot h er 
i n v e sti g ati o n al a n d 
a nti n e o pl a sti c 
t h er a pi e s n ot p art of 
t h e st u d y
Ot h er i n v e sti g ati o n al t h er a pi e s m u st n ot b e u s e d w hil e t h e p ati e nt i s o n t h e st u d y. 
A nti c a n c er t h er a p y ( c h e m ot h er a p y, all S E R M S (i n cl u di n g r al o xif e n e) bi ol o gi c or 
r a di ati o n t h er a p y, a n d s ur g er y) ot h er t h a n t h e st u d y tr e at m e nt s m u st n ot b e gi v e n t o 
p ati e nt s w hil e t h e p ati e nt i s o n t h e st u d y m e di c ati o n. If s u c h a g e nt s ar e r e q uir e d f or a 
p ati e nt, t h e n t h e p ati e nt m u st b e di s c o nti n u e d fr o m t h e st u d y.
H er b al 
pr e p ar ati o n s/ 
m e di c ati o n s
H er b al pr e p ar ati o n s/ m e di c ati o n s ar e pr o hi bit e d t hr o u g h o ut t h e st u d y. T h e s e h er b al 
m e di c ati o n s i n cl u d e, b ut ar e n ot li mit e d t o bl a c k c o h o s h, St. J o h n’ s W ort, K a v a, 
e p h e dr a ( m a h u a n g), gi n g k o bil o b a, d e h y dr o e pi a n dr o st er o n e ( D H E A), y o hi m b e, s a w 
p al m ett o, a n d gi n s e n g. P ati e nt s s h o ul d st o p u si n g t h e s e h er b al m e di c ati o n s 7 d a y s 
pri or t o fir st d o s e of st u d y dr u g.


P h as e 1 b C o ns e nt
P a g e 2 5 of 2 5 C C # 1 4 5 5 1 5
I C F v 0 7- 0 1- 2 0 1 9
R a h ul A g g ar w al, M D
LI S T O F M E DI C A TI O N S T O B E U S E D WI T H C A U TI O N
C at e g or y
Dr u g N a m e
M o d er at e 
C Y P 3 A 4/ 5 
i n hi bit or s
A pr e pit a nt, a m pr e n a vir, a s af o eti d a r e si n ( F er ul a a s af o eti d a) ci m eti di n e, cri z oti ni b, 
dilti a z e m, f al d a pr e vir, i m ati ni b, i s a v u c o n a z ol e, n et u pit a nt, nil oti ni b, t ofi s o p a m, 
S c hi s a n dr a s p h e n a nt h er a ( n a n w u w ei zi), v er a p a mil
M o d er at e
C Y P 3 A 4/ 5
i n d u c er s
B o s e nt a n, d a br af e ni b, ef a vir e n z, etr a viri n e, g e ni st ei n,l o pi n a vir 5 , m o d afi nil, n af cilli n, 
t el otri st at
S e n siti v e
C Y P 3 A 4/ 5
s u b str at e s
Al p h a- di h y dr o er g o cr y pti n e, a pr e pit a nt, at or v a st ati n, a v a n afil, b o s uti ni b, br oti z ol a m, 
b u d e s o ni d e, b u s pir o n e, c o bi m eti ni b, d arif e n a ci n, d a s ati ni n b, e b a sti n e, el etri pt a n, 
e pl er e n o n e, e v er oli m u s, f el o di pi n e, fl uti c a s o n e, gr a z o pr e vir, i br ut ni b, i s a v u c o n a z ol e, 
i v a br a di n e, i v a c aft or, , l e v o m et h a d yl ( L A A M), l o mit a pi d e, l o v a st ati n, l u m ef a ntri n e, 
l ur a si d o n e, m ar a vir o c, mi d a z ol a m, mi d o st a uri n, n al o x e g ol, n er ati ni b, ni s ol di pi n e, 
p er o s pir o n e, q u eti a pi n e, ri d af or oli m u s, sil d e n afil, si m e pr e vir, si m v a st ati n, ti c a gr el or, 
tili di n e, t ol v a pt a n, tri a z ol a m, uli pri st al, v ar d e n afil, v e n et o cl a x, vi cri vir o c, v o cl o s p ori n
B S E P i n hi bit or s
Al e cti ni b, at or v a st ati n, br o m o cri pti n e, c a n d e s art a n, cl o b et a s ol, cl of a zi mi ni e, d a bi g atr a n, 
di p yri d a m ol e, gl y b uri d e, gr a z o pr e vir, l e di p a s vir, mif e pri st o n e, pi o glit a z o n e, 
r e s er pi n e,rif a m y ci n, si m e pr e vir, t el mi s art a n,ti m c o d ar, tr o glit a z o n e, v ali n o m y ci n, 
v el p at a s vir
M A T E 1 a n d 
O C T 2 s u b str at e s
A c y cl o vir, c e p h al e xi n, ci m eti di n e, f e x of e n a di n e, g a n ci cl o vir, gl y c o p yrr o ni u m, m etf or mi n, 
pi n d ol ol, pli si c ai ni d e, r a niti di n e, t o p ot e c a n, v ar e ni cli n e
O C T 1/ 2 
s u b str at e s
A m a nt a di n e, 6- b et a- h y dr o x y c orti s ol, c ar b o pl ati n, ci s pl ati n, c e p h al e xi n, c e p hr a di n e, 
i pr atr o pi u m, l a mi v u di n e, li n a gli pti n, m etf or mi n, o x y pl ati n, o x y b ut y ni n, p h e nf or mi n, 
pi c o pl ati n, pil si c ai ni d e, pi n d ol ol, r a niti di n e, s or af e ni b, tr o pi s etr o n, tr o s pi u m, 
u m e cli di ni u m, a n d zi d o v u di n e
B C R P s u b str at e s D a u n or u bi ci n, d ol ut e gr a vir, d o x or u bi ci n, h e m at o p or p h yri n, i m ati ni b, m et h otr e x at e, 
mit o x a ntr o n e, pit a v a st ati n, r o s u v a st ati n, iri n ot e c a n, et hi n yl e str a di ol, si m v a st ati n, 
s ulf a s al a zi n e, s of o s b u vir, t e n of o vir, t o p ot e c a n, v e n et o cl a x
M e di c ati o n s t h at 
c arr y a p o s si bl e 
ri s k f or Q T 
pr ol o n g ati o n
Alf u z o si n, a p o m or p hi n e, ari pi pr a z ol e, art e ni m ol + pi p er a q ui n e , a s e n a pi n e, at o m o x eti n e, 
b e d a q uili n e, b e n d a m u sti n e, b ort e z o mi b, b o s uti ni b, b u pr e n or p hi n e, c a b o z a nti ni b, 
c a p e cit a bi n e, c eriti ni b, cl o mi pr a mi n e, cri z oti ni b, cl o z a pi n e, c y a m e m a zi n e 
( c y a m e pr o m a zi n e), d a br af e ni b, d a s ati ni b, d e g arili x, d el a m a ni d, d e si pr a mi n e, 
d e x m e d et o mi di n e, d ol a s etr o n, ef a vir e n z, eli gl u st at, e pir u bi ci n, eri b uli n m e s yl at e, 
e z o g a bi n e(r eti g a bi n e), f a m oti di n e, f el b a m at e, fi n g oli m o d, fl u p e nti x ol, g e mifl o x a ci n, 
gr a ni s etr o n, h y dr o c o d o n e- E R, il o p eri d o n e, i mi pr a mi n e ( m eli pr a mi n e), i sr a di pi n e, 
k et a n s eri n, l a p ati ni b, l e n v ati ni b, l e u pr oli d e, lit hi u m, m el p er o n e, mi d o st a uri n, 
mif e pri st o n e, mir a b e gr o n, mirt a z a pi n e, m o e xi pril/ H C T Z, n e cit u m u m a b, ni c ar di pi n e, 
nil oti ni b, n orfl o x a ci n, n ortri pt yli n e, n u si n er s e n, ofl o x a ci n, o si m erti ni b, o x yt o ci n, 
p ali p eri d o n e, p al o n o s etr o n, p a n a bi n o st at, p a sir e oti d e, p a z o p a ni b, p erfl utr e n li pi d 
mi cr o s p h er e s, p er p h e n a zi n e, pil si c ai ni d e, pi m a v a n s eri n, pi p a m p er o n e, pr o m et h a zi n e, 
pr ot hi p e n d yl, ril pi viri n e, ri s p eri d o n e, r o mi d e p si n, s erti n d ol e, s or af e ni b, s u niti ni b, 
t a m o xif e n, ti pir a cil/trifl uri di n e, ti z a ni di n e, t olt er o di n e, t or e mif e n e,tri mi pr a mi n e, 
tr o pi s etr o n, v ar d e n afil, v e m ur af e ni b, v e nl af a xi n e, v ori n o st at, zi pr a si d o n e