A Selective Frontline Cabazitaxel Therapeutic Pathway for Castration-Resistant Prostate Cancer With Integrated Biomarkers
Phase: PHASE2
Conditions: Hormone-Resistant Prostate Cancer, Stage IV Prostate Adenocarcinoma
Sponsor: University of California, Davis

Confidential 
 
 
A Selective Cabazitaxel Therapeutic Pathway for Castration-Resistant 
Prostate Cancer with Integrated Biomarkers 
 
Protocol Number(s):  
UCDCC#261; SA-2014-11231 
Indication: 
Castration-Resistant Prostate Cancer (CRPC) 
Phase: 
II 
Funding Source: 
Sanofi 
Therapeutic Area: 
Urologic Oncology 
Compound: 
 
Jevtana®/cabazitaxel 
 
Coordinating Center: 
 
 
University of California, Davis Comprehensive Cancer Center 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator:             Christopher P. Evans, MD 
 
University of California, Davis (UCD) 
Department of Urology 
UC Davis Comprehensive Cancer Center 
 
 
 
 
Co-Investigators: 
Primo Lara, MD 
 
University of California, Davis (UCD) 
UC Davis Comprehensive Cancer Center 
 
 
 
 
Chong-xian Pan MD, PhD 
 
University of California, Davis (UCD) 
 
UC Davis Comprehensive Cancer Center 
 
 
 
 
 
 
 
 

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Statistician: 
Blythe Durbin-Johnson, Ph.D. 
 
Principal Statistician 
 
Public Health Sciences 
 
Division of Biostatistics 
 
 
 
  
 
 
 
 
 
 
Participating Centers:  
UC Davis Comprehensive Cancer Center  
 
 
 
 
          
Protocol History: 
Original 
 
June 25, 2015 
 
Revision  
September 22, 2015 
  
Revsion 
 
March 15, 2016 
 
Revision  
July 7, 2016 
 
Revision  
June 1, 2017 
 
Revision  
September 15, 2017 
 
Revision  
May 23, 2018 
 
            
IND Exempt #: 
 
129871 
 
IND Sponsor:  
 
University of California Davis Comprehensive Cancer Center 
 
 

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PROTOCOL SIGNATURE PAGE 
 
 
Protocol Number: UCDCC#261  
 
 
Protocol Title: A Selective Cabazitaxel Therapeutic Pathway for Castration-Resistant Prostate 
Cancer with Integrated Biomarkers 
 
I have read this protocol and agree that it contains all necessary details for carrying out this 
study. I will conduct the study as outlined herein and will complete the study within the time 
designated, in accordance with all stipulations of the protocol and in accordance with Good 
Clinical Practices, local regulatory requirements, and the Declaration of Helsinki.  
 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that 
they are fully informed regarding the study agent(s) and the conduct of the study.  
 
 
 
__________________________________ 
Investigator Name (print)                          
 
 
__________________________________ 
Investigator Signature  
 
 
_____________________ 
Date  

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STUDY SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PSA nadir ≥ 0.2, or an ADT response 
duration < 16 months, or a Gleason 8 or 
greater 
  DEATH OR CUT-OFF DATE 
TREATMENT   
(continue treatment until disease progression, unacceptable 
toxicity or completion of 6 cycles)  
Cabazitaxel 20 mg/m2 IV every 3 weeks   
+   
Prednisone 5 mg PO twice daily 
END OF TREATMENT 
FOLLOW UP PERIOD  
(every 12 weeks) 
SCREENING  
Up to 4 weeks 

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LIST OF ABBREVIATIONS 
 
ABCB1 
ATP-binding cassette sub-family B member 1 
ADT  
Androgen Deprivation Therapy 
AE  
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Amino Transferase 
ANC 
Absolute Neutrophil Count 
AR 
Androgen Receptor 
AST 
Aspartate Amino Transferase 
AUC  
Area Under Curve 
BP 
Blood Pressure 
BSA  
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CBZ 
Cabazitaxel 
CHF 
Congestive Heart Failure 
CI 
Confidence Interval 
CNS 
Central Nervous System 
Cmax 
Maximum plasma concentration 
CR 
Complete Response  
CRF 
Case Report Form 
CRPC 
Castrate Resistant Prostate Cancer 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP3A 
Cytochrome P3A 
DLT 
Dose Limiting Toxicity 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDTA 
Ethylene Diamine Tetraacetic Acid 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte Colony Stimulating Factor 
h / hr 
Hour 
Hb 
Hemoglobin 
HCG 
Human Chorionic Gonadotrophin 
HDPE 
High Density Polyethylene 
HIV 
Human Immunodeficiency Virus 
HPBMC 
Human Peripheral Blood Mononuclear Cells 
HPFB/TPD 
Health Products and Food Branch/Therapeutic Products Directorate 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Identification (number) 
IRB/EC 
Institutional Review Board/ Ethics Committee 
ITT 
Intention To Treat  
i.v. 
Intravenous 
Kel 
Elimination rate constant 
Kg 
Kilogram 

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L 
Litre 
LD 
Longest Diameter 
LDH 
Lactate Dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
Minute 
ml 
Milliliter 
MBC 
Metastatic Breast Cancer 
MRI 
Magnetic Resonance Imaging 
MRP1 
Multidrug resistance-associated protein 1 
MTD 
Maximum Tolerated Dose  
MTX 
Mithoxantrone 
MUGA 
Multi Gated Acquisition Scan 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NSAIDS 
Non-Steroidal Anti-Inflammatory Drugs 
NOEL 
No Observed Effect Level 
ORR 
Overall Response Rate 
OS 
Overall Survival 
PCNA 
Proliferating Cell Nuclear Antigen 
pCR 
Pathological Complete Response 
PCGW2 
Prostate Cancer Clinical Trials Working Group 
PD 
Progressive Disease 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PO 
Per os/ By mouth / Orally 
PR 
Partial Response  
PSA 
Prostate Specific Antigen 
PT 
Prothrombin Time 
PS 
Performance Status 
PTT 
Partial Thromboplastin Time 
q 
Every 
RBC 
Red Blood Cells 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SD 
Stable Disease 
SGOT 
Serum Glutamate Oxaloacetate Transaminase 
SGPT 
Serum Glutamate Pyruvate Transaminase 
SOC 
Standard of Care 
Tmax 
Time at which Cmax is reached 
t1/2 
Elimination half-life 
ULN 
Upper Limit of Normal 
µg 
Microgram 
VEGF 
Vascular Endothelial Growth Factor 
Vz 
Volume of Distribution 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 
 

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TABLE OF CONTENTS 
STUDY SCHEMA...........................................................................................................................4 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ...............................................................................................................9 
1.1 
Background and Study Rationale.............................................................................9 
1.2 
Cabazitaxel (Jevtana®) ..........................................................................................10 
1.3 
Correlative Studies .................................................................................................11 
2. 
STUDY OBJECTIVES AND ENDPOINTS .....................................................................12 
3. 
SUBJECT SELECTION ....................................................................................................13 
3.1 
Inclusion Criteria ...................................................................................................13 
3.2 
Exclusion Criteria ..................................................................................................14 
3.3 
Inclusion of Minorities ...........................................................................................15 
4. 
INVESTIGATIONAL PLAN ............................................................................................15 
4.1 
Treatment Schedule ...............................................................................................15 
4.2 
Premedication for Cabazitaxel Treatment .............................................................15 
4.3 
Antidiarrheal Medications .....................................................................................15 
4.4 
Toxicities and Dose Adjustments for Cabazitaxel .................................................16 
4.5 
Dose Modifications for Prednisone .......................................................................21 
4.6 
Concomitant Medications ......................................................................................21 
5. 
DRUG INFORMATION ...................................................................................................24 
5.1 
Cabazitaxel (Jevtana®) ..........................................................................................24 
5.2 
Prednisone ..............................................................................................................27 
6. 
ASSESSMENT OF EFFECTS ..........................................................................................29 
6.1 
Safety assessment...................................................................................................29 
6.2 
Efficacy assessments ..............................................................................................29 
7. 
STUDY CALENDAR .......................................................................................................30 
8. 
CORRELATIVE STUDIES………………………………………………………..……33 
9. 
SAFETY AND REPORTING REQUIREMENTS ...........................................................34 
9.1 
Adverse Event Definition ......................................................................................34 
9.2 
Adverse Event Documentation ..............................................................................35 
9.3 
Severity of Adverse Events ....................................................................................35 
9.4 
Serious Adverse Event Definition .........................................................................35 
9.5 
Procedures for Reporting Serious Adverse Events (SAEs) ...................................36 
10. 
STATISTICAL CONSIDERATIONS...............................................................................38 
10.1 
Study Design and Overview of Primary and Secondary Endpoints ......................38 
10.2 
Sample Size Estimation /Accrual Rate ..................................................................38 

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10.3 
Evaluation of Efficacy ...........................................................................................39 
10.4 
Evaluation of Safety ...............................................................................................39 
11. 
ADMINISTRATIVE REQUIREMENTS .........................................................................39 
11.1 
Good Clinical Practice ...........................................................................................39 
11.2 
Ethical Considerations ...........................................................................................40 
11.3 
Required Documentation .......................................................................................40 
11.4 
Study Registration ..................................................................................................40 
11.5 
Patient Information and Informed Consent............................................................40 
11.6 
Protocol Deviations ................................................................................................41 
11.7 
Patient Confidentiality ...........................................................................................41 
11.8 
Protocol Compliance ..............................................................................................41 
11.9 
On-site Audits ........................................................................................................41 
11.10 Drug Accountability and Disposal .........................................................................42 
11.11 Premature Closure of the Study .............................................................................42 
11.12 Record Retention ...................................................................................................42 
11.13 Quality Assurance and Control ..............................................................................42 
12. 
USE OF INFORMATION .................................................................................................43 
13. 
REFERENCES ..................................................................................................................44 
14. 
APPENDICES ...................................................................................................................45 
14.1 
Performance Status Criteria ...................................................................................45 
14.2 
List of strong CYP3A inhibitors ............................................................................46 
14.3 
List of strong CYP 3A inducers .............................................................................47 
14.4 
Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 ..........................48 
14.5 
Correlate Sample Submission Form ......................................................................55 
14.6 
Multicenter Guidelines...........................................................................................56 
14.7 
Data Submission Schedule .....................................................................................57 
 
 
 

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1. 
INTRODUCTION 
 
1.1 
Background and Study Rationale 
 
Castration resistant prostate cancer (CRPC) remains an incurable and heterogeneous disease. 
Patients have variable responses to initial androgen deprivation therapy1 and subsequent agents 
inhibiting the androgen axis once it is castration resistant. Some of the second line androgen axis 
inhibitors’ lack of efficacy can be predicted by the response to primary androgen deprivation 
therapy. As such, a potential exists to identify these patients and treat them effectively with 
chemotherapy.  Cabazitaxel was approved in 2011 for the treatment of patients with CRPC who 
were previously treated with a docetaxel-containing regimen. 2  Cabazitaxel will be the study 
agent in the clinical trial.  
 
Patients with an initial limited response to primary androgen deprivation therapy or whose 
tumors are of high Gleason score (8-10) tend to have minimal subsequent response to abiraterone 
and enzalutamide as frontline metastatic CRPC treatments. 3-6 Data suggest that 25-33% of 
patients will not respond to abiraterone or enzalutamide. Stratification of response to initial 
androgen deprivation therapy by prostate specific antigen (PSA) level suggests that a PSA nadir 
of <0.2, 0.2-4.0, and >4.0 results in median overall survival of 75, 44, and 13 months, 
respectively. 1 In addition, those with a duration of response <16 months or an initial Gleason 
score tumor >= 8 have a significantly worse (overall survival) OS.7 Patients with an initial 
limited response to ADT also have limited responses to abiraterone and enzalutamide. Data 
suggest that patients receiving docetaxel after abiraterone or enzalutamide have approximately a 
40% reduced response. Additionally, in CRPC patients who have received a prior taxane 
(docetaxel), primary resistance to subsequent abiraterone or enzalutamide is seen in up to 35% of 
patients (based on observations from the COU-301 and AFFIRM trials). We propose to select 
patients with a PSA nadir ≥0.2, or an ADT response duration <16 months, or a Gleason 8 or 
greater for therapy with cabazitaxel. We will collect serial serum to interrogate for development 
of a gene signature consistent with response and eventual resistance to cabazitaxel. The PSA will 
be measured at UC Davis and the definitions used for inclusion are specific to UC Davis testing 
methodology. 
 
These data raises the question of how best to manage mCRPC patients with poor prognostic 
features. Based on the likelihood of attaining more rapid anti-tumor responses, one approach to 
poor prognosis disease would be to utilize cytotoxic chemotherapy. In a phase III trial, the novel 
anti-microtubule agent cabazitaxel has been shown to significantly increase overall survival in 
metastatic CRPC previously treated with docetaxel.2 Importantly, the superiority of cabazitaxel 
over the comparator treatment (mitoxantrone) persisted in patients with measurable visceral or 
soft-tissue metastatic disease and those with multiple poor prognosis factors. In view of these 
facts, we will test the hypothesis that treatment of this patient population with cabazitaxel will 
result in a Therapeutic response defined as a PSA response rate > 50% reduction from baseline. 
This will exceed historical controls for this patient population.  
 
 
 

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1.2 
Cabazitaxel (Jevtana®) 
 
1.2.1 Preclinical Data 
 
Cabazitaxel (also known as XRP6258, RPR116258A) is a semisynthetic taxane promoting tublin 
assembly and stabilizing microtubules.  It is derived from 10-deacetyl Baccatin III, which is 
extracted from European yew needles. It was selected for development based on a better 
antiproliferative activity on resistant cell lines than docetaxel. Using cell lines with acquired 
resistance to doxorubicin, vincristine, vinblastine, paclitaxel and docetaxel, the resistance factors 
ranged from 1.8 to 10 and 4.8 to 59, for cabazitaxel and for docetaxel, respectively.  Cabazitaxel 
exhibited a broad spectrum of in vivo antitumor activity, not only in docetaxel -sensitive tumor 
models, but also in tumors models in which docetaxel was either poorly active or not active. The 
best antitumor efficacy was obtained with the schedules allowing the administration of the 
highest amount of drug. In addition, this compound was found to penetrate the blood brain 
barrier and marked antitumor activity was obtained in nude mice bearing intracranial 
glioblastomas. 
 
In general, nonclinical data suggest that the toxicity effects observed with cabazitaxel are 
consistent with those reported for other taxane class anticancer drugs. 
 
More information on the preclinical data is available in the clinical Investigator’s Brochure.  
 
1.2.2 Summary of Clinical Data  
 
In single agent, 3 Phase I studies were conducted to determine the schedule and the 
recommended dose, one study investigating the disposition of radiolabeled cabazitaxel, one 
Phase 2 study in patients with metastatic breast cancer (MBC), and one Phase 3 study in patients 
with mCRPC. One Phase I/II study has been conducted with cabazitaxel plus prednisone in 
combination with capecitabine. 
 
The 3 Phase 1 studies in solid tumors (TED6188, TED6189, TED6190) have been completed. 
There were 2 partial responses in patients with prostate cancer in Phase 1 studies evaluating the 
every 3 week schedule; 2 PR out of 8 patients with metastatic HRPC in TED6190 at 25 mg/m2 
suggesting potential biological and clinical activity in patients with prostate cancer. 
 
The safety profile was comparable in TED6188 and TED6190, with the intermittent schedule 
(1hour infusion every 3 weeks).  The dose limiting toxicity (DLT) of cabazitaxel was 
neutropenia and its infectious complications at the highest dose tested, 30 mg/m² in TED6188 
and 25 mg/m² in TED6190. 
 
As a result, the dose levels of 20 mg/m² and 25 mg/m² every 3 weeks were defined as the 
recommended doses for further clinical development with the intermittent schedule. 
 
In TED6189 with the weekly schedule, the maximum tolerated dose (MTD) was reached at 12 
mg/m², at which the DLT was diarrhea.  As a result, the dose level of 10 mg/m² was defined as 
the recommended dose for further clinical development with this weekly schedule. 
 

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One Phase 2 study in patients with taxane- and/or anthracycline-resistant metastatic breast cancer 
has been completed (ARD6191). In this study patients were treated with a starting dose of 
20 mg/m2 cabazitaxel every 3 weeks with the option to dose-escalate cabazitaxel based on 
favorable tolerability at Cycle 1. In 20 of 71 patients, the cabazitaxel dose was escalated from 20 
to 25 mg/m2 after the first cycle. The most frequently occurring toxicities overall were Grade 3 
and 4 neutropenia (73.2%), fatigue (50.7%), nausea (43.7%), diarrhea (39.4%), myalgia (25.4%), 
anorexia (25.4%), weight loss (25.4%), and vomiting (23.9%). The overall response rate was 
14.1% with 2 complete responses (CR) and 8 partial responses (PR). 
 
One Phase 3 study was conducted in mCRPC patients previously treated with docetaxel 
containing regimen. This study compared cabazitaxel (CBZ) plus prednisone to mitoxantrone 
(MTX) plus prednisone (EFC6193). A total of 755 patients were randomized (378 patients in 
CBZ arm and 377 patients in MTX arm). A statistically significant increase in OS was observed 
in patients treated with CBZ plus prednisone compared to patients treated with MTX plus 
prednisone, with a HR of 0.70 (95%CI: 0.59 – 0.83), a log-rank p-value of 0.0001. The median 
OS was 15.1 months (95%CI: 14.1 – 16.3) in CBZ arm versus 12.7 months (95%CI: 11.6 – 13.7) 
in MTX arm. 
 
Refer to the Investigator’s Brochure for additional information about cabazitaxel. 
 
1.3 
Correlative Studies 
 
We will collect serum and tumor tissue samples for molecular markers or signature predictive of 
cabazitaxel benefit (to include status of androgen receptor (AR) pathway, AR splice variants, 
androgen biosynthetic pathway genes, ATP-binding cassette sub-family B member 1 (ABCBI), 
multidrug resistance-associated protein 1 (MRP1), and other mediators of taxane resistance). The 
correlative studies will seek to identify both signatures of resistance to AR axis inhibitors and 
signatures of sensitivity to cabazitaxel. 
 
To validate and establish controls for these correlative studies prior to testing of clinical samples, 
we will establish an MTA to obtain laboratory grade cabazitaxel for pre-clinical use. A variety of 
castration-resistant prostate cancer cell lines and xenografts will be treated with Jevtana and 
samples assayed for correlative biomarkers. This will validate assay standards via pre-clinical 
samples rather than limited quantities of liquid biopsy material (cfDNA, CTCs) or solid biopsy 
material. The MTA will request for cabazitaxel formulations for both in vitro and in vivo 
experiments. No funding is requested for these experiments.  
 
 
 
 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
 
Primary Objectives: 
The primary objective of this study is: 
To test whether men with a poor initial response to ADT have a better therapeutic response to 
cabazitaxel as compared to historical controls of frontline metastatic CRPC therapy with 
abiraterone or enzalutamide.  Therapeutic response is defined as a PSA response rate > 50% 
reduction from baseline. 
 
Secondary Objectives: 
The secondary objectives of this study are: 
• To determine the RECIST v1.1 response rate, progression free survival (PFS) by 
PCWG2 criteria, and overall survival (OS).  
 
• To evaluate safety and toxicity profile of cabazitaxel in patients with CRPC. 
Biological Objectives:  
• 
To collect serum and tumor tissue samples for molecular markers or signature 
predictive of cabazitaxel benefit (to include status of AR pathway, androgen 
biosynthetic pathway genes, ABCBI, MRP1, and other mediators of taxane 
resistance).  
 
Primary Endpoint:  
PSA response rate (defined as > 50% reduction from baseline)   
 
Secondary Endpoints:  
 
Safety:  
• 
Adverse events, serious adverse events, and discontinuations (CTCAE 4.03) 
 
Efficacy:  
 
• 
RECIST response (Radiographic disease progression) 
 
• 
Progression-free survival (PFS) defined as the time interval between the date of 
enrollment and the date of the first documentation by PCWG2 criteria. 
 
• 
Overall survival defined as the time interval from the date of enrollment to the date 
of death due to any cause 

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Biomarkers:  
 
•  To interrogate serum and tumor tissue specimens for molecular markers or signature 
predictive of cabazitaxel benefit (to include status of AR pathway, androgen 
biosynthetic pathway genes, ABCB1, MRP1, and other mediators of taxane 
resistance, among others). 
 
3. 
SUBJECT SELECTION 
 
Patients will be recruited in the medical, urologic, and radiation oncology clinics of the 
University of California Davis Medical Center and participating centers.  The study population 
will include those patients with newly confirmed castration-resistant prostate cancer or those 
who have progressed following up to one treatment with abiraterone or enzalutamide. The 
number of patients enrolled on this phase II study is 45.  
 
3.1 
Inclusion Criteria  
 
Patients will be men with new onset CRPC and each patient must meet all of the following 
inclusion criteria to be enrolled in the study: 
 
1. Histologically confirmed prostate adenocarcinoma. 
 
2. Metastatic disease. 
 
3. Able and willing to provide informed consent and to comply with the study procedures. 
 
4. Castration resistant disease defined as evidence of radiological and/or PSA progression 
despite castrate levels of testosterone (serum testosterone < 50 ng/dL (1.7 nmol/L)). For 
PSA progression, there must be at least 2 sequential rises at a minimum of 1-week 
intervals. The first PSA value must be ≥0.2 (Prostate Cancer Working Group 2 (PCWG2) 
criteria). 
 
5. Patient may have been treated with up to one androgen receptor pathway inhibitor prior to 
enrollment into this trial. 
 
6. Age ≥18. 
 
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 
 
8. At least 21 days have passed since completing radiotherapy (exception for radiotherapy: at 
least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field or limited-
field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of 
registration. 
 
9. At least 21 days have passed since receiving any investigational agent at the time of 
registration. 

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10. At least 21 days have passed since major surgery. 
 
11. Neuropathy ≤ grade 1 at the time of registration. 
 
12. Has recovered from all therapy-related toxicity to ≤ grade 2 (except alopecia, anemia and 
any signs or symptoms of androgen deprivation therapy) at the time of registration. 
 
13. Poor prognosis disease as defined by any of the following:  
• PSA nadir ≥ 0.2, or  
• Gleason score 8-10, or  
• Time from ADT initiation to CRPC of <16 months. 
 
14. Adequate hematologic, hepatic, and renal function: 
• Hemoglobin ≥ 90 g/L  
• Neutrophils ≥ 1.5 x 109 /L 
• Platelets ≥ 100 x 109/L 
• AST < 1.5 x ULN 
• ALT < 1.5 x ULN  
• Bilirubin ≤ 1.0 x ULN (exceptions for Gilbert’s syndrome)  
• Creatinine ≤ 1.5 x ULN 
 
3.2 
Exclusion Criteria 
 
Patients meeting any of the following exclusion criteria are not to be enrolled in the study. 
 
1. Prior therapy with cabazitaxel or to other drugs formulated with polysorbate 80. 
 
2. Prior taxanes for CRPC. 
 
3. (Deleted as of Rev May 23, 2018.)  
 
4. Other condition, illness, psychiatric condition, or laboratory abnormality that may 
increase the risk associated with administration of cabazitaxel,  study participation, or 
may interfere with the interpretation of study results and in the judgment of the 
investigator would make the patient inappropriate for entry into this study. 
 
5. Histologic evidence of small cell/neuroendocrine prostate cancer. 
 
6. Patients with reproductive potential who do not agree to use accepted and effective 
method of contraception during the study treatment period and up to 6 months after the 
last administered dose. The definition of “effective method of contraception” will be 
based on the investigator’s judgment.  
 
 

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3.3 
Inclusion of Minorities 
 
Men of all races and ethnic groups are eligible for this trial. 
 
 
4. 
INVESTIGATIONAL PLAN 
 
4.1 
Treatment Schedule  
 
Cabazitaxel 20 mg/m2  intravenous infusion over 1 hour (Day 1) every 3 weeks, plus prednisone 
10mg orally given daily.  A cycle is defined as a 3-week (21 days) period.  
 
Study drug will be administered only to eligible patients under the supervision of the investigator 
or identified subinvestigator(s).  
 
 
 
 
 
 
4.2 
Premedication for Cabazitaxel Treatment 
 
Premedication is recommended at least 30 minutes prior to each dose of cabazitaxel with the 
following intravenous medications to reduce the risk and/or severity of hypersensitivity: 
 
• 
antihistamine (dexchlorpheniramine 5 mg, or diphenhydramine 25 mg or equivalent 
antihistamine), 
 
• 
corticosteroid (dexamethasone 8 mg or equivalent steroid), 
 
• 
H2 antagonist (ranitidine 50 mg or equivalent H2 antagonist). 
 
Antiemetic prophylaxis is recommended and can be given orally or intravenously as needed. 
Appropriate prophylactic antiemetic therapy will be according to local hospital procedures. 
 
 
4.3 
Antidiarrheal Medications 
 
Severe diarrhea may occur and death related to diarrhea and electrolyte imbalance has been 
reported with cabazitaxel.  Intensive treatment with antidiarrheal medications along with 
hydration is recommended.  
 
 
 
 
 
Agent 
Dose 
Route 
Schedule 
Cabazitaxel 
20 mg/m2 
I.V. 
q3w 
Prednisone 
5 mg  
P.O. 
Twice Daily 

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4.4 
Toxicities and Dose Adjustments for Cabazitaxel  
 
Every effort will be made to administer the full dose regimen to maximize dose-intensity. 
 
Doses will be reduced for hematologic and other adverse events. Dose adjustments are to be 
made according to the system showing the greatest degree of toxicity. Adverse events will be 
graded using the NCI Common Terminology Criteria for Adverse Events Version 4.03 
(CTCAE). 
 
The guidelines which follow outline dose adjustments for several of these toxic effects. If a 
patient experiences several adverse events and there are conflicting recommendations, please use 
the recommended dose adjustment that reduces the dose to the lowest level. Doses that have been 
reduced for toxicity must not be re-escalated. 
 
Table 1. Cabazitaxel Reduction Level 
 
Starting dose 
20 mg/m2 
-1 
15 mg/m2 
Upon dose reduction, administer G-CSF (or equivalent) per institutional or standard 
guidelines in subsequent cycles. Patients requiring a second dose reduction are to be 
taken off study. 
 
 
A treatment delay ≥4 days should be justified and documented in the source notes and case 
report forms. Treatment may be delayed no more than 2 weeks to allow recovery from acute 
toxicity. In case of treatment delay greater than 2 weeks, patient should discontinue study 
treatment, unless there is strong evidence of clinical benefit to justify continuation of dosing with 
study treatment. 
 
4.4.1 Hematologic and Non-Hematologic Adverse Events 
 
 

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Table 2: Dose Modifications for cabazitaxel for Hematologic Toxicity 
Toxicity 
Grade 
Dose Modification 
Neutropenia 
Grade 2 
If not recovered on D21, delay1 next infusion until 
recovery to grade ≤1 (neutrophil ≥1.5x109/L). 
1st episode: no dose reduction required. 
2nd episode: reduce by 1 dose level. 
Grade 3 & 4 
No dose reduction if isolated and duration ≤7 days.   
If duration more than 7 days or not recovered on D21, 
delay1 next infusion until ANC ≥1.5x109/L and: 
1st episode: Administer prophylactic G-CSF treatment 
in subsequent cycles or reduce by 1 dose level. 
2nd episode: Withdraw from study treatment; or 1st 
episode despite prophylactic G-CSF: Reduce dose 
by 1 dose level. 
2nd episode despite prophylactic G-CSF: Withdraw 
from study treatment. 
Febrile 
neutropenia or 
neutropenic 
infection 
Grade 3 & 4 
Delay1 next infusion until recovery and ANC ≥1.5 x 
109/L and: 
1st episode: reduce the dose and administer 
prophylactic G-CSF treatment in subsequent cycles 
if available. 
2nd episode: Withdraw from study treatment. 
Thrombocytopenia 
Grade 2 
Delay1 next infusion until recovery to grade ≤ 1 
(platelets ≥75 x 109/L). 
No dose reduction required. 
Grade 3 & 4 
Delay1 infusion until platelets ≥75 x 109/L. If grade 3 
without delay, no dose reduction required. 
If grade 4 with or without delay, or grade 3 with delay 
1st episode: Reduce dose by 1 dose level. 
2nd episode: Withdraw from study treatment in case of 
recurrence. 
Dose reduction levels provided in Table 1. 
1 Maximum of 2 weeks delay, otherwise the patient will be withdrawn from study treatment. 
 
Blood counts will be performed in case of fever or infection. Blood count should be monitored 
weekly for the first cycle to determine if granulocyte colony-stimulating factor or dosage 
modification is needed. Study treatment should not be given to patients with neutrophil counts 
<1.5 x109 /L. 
Deaths due to sepsis following severe neutropenia have been reported in patients treated with 
cabazitaxel. Neutropenic complications should be managed promptly with antibiotic support and 

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use of G-CSF should be considered according to American Society of Clinical Oncology 
(ASCO) guidelines1.  
No dose modification will be made for anemia; patients will be supported appropriately by the 
treating physician. 
 
Table 3: Dose Modifications for cabazitaxel for Non-Hematologic Toxicity 
Toxicity 
Grade 
Dose Modification 
Diarrhea 
Grade 2 
Delay1 next infusion until recovery (grade ≤1) 
No dose reduction required. 
Grade 3 & 4 
Delay1 next infusion until recovery (grade ≤1): 
1st episode: Reduce dose by 1 dose level. 
2nd episode: Withdraw from study treatment. 
 
Stomatitis 
Grade 2 
Delay1 next infusion until recovery (grade ≤1) 
No dose reduction required. 
Grade 3 & 4 
Delay1 next infusion until recovery (grade ≤1): 
1st episode: Reduce dose by 1 dose level. 
2nd episode: Withdraw from study treatment. 
 
Cutaneous 
Reactions 
Grade 2 
Delay1 next infusion until recovery (grade ≤1). 
No dose reduction required. 
Grade 3 
Delay1 next infusion until recovery (grade ≤1): 
1st episode: Reduce dose by 1 dose level. 
2nd episode: Withdraw from study treatment. 
Grade 4 
Withdraw from study treatment. 
Creatinine 
increase 
Grade 2, 3, & 4 
No delay; in case of creatinine >1 x ULN:calculate 
creatinine clearance using the  Cockcroft-Gault 
equation on D21: 
if ≥60 ml/min, no dose modification 
if clearance ≥40 ml/min and < 60ml/min, reduce 
dose by one dose level 
if clearance <40 ml/min, Withdraw from study 
treatment. 
 
Neurological 
toxicity2 
Grade 2 
No delay. 
Reduce by 1 dose level 
                                                 
1  
Smith, TJ, Khatcheressian GL, Lyman GH, et al: 2006 Update of Recommendations for the 
Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. J Clin Oncol 24: 
3187-3205. 2006 

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Grade 3 & 4 
Withdraw from study treatment. 
Bilirubin 
Elevation 
Grade 2 
Delay1 until recovery to bilirubin ≤1.0 x UNL and 
reduce dose by 1 dose level 
Grade 3 & 4 
Withdraw from study treatment. 
Transaminases 
Elevation 
Grade 2 
Delay1 until recovery to AST/ALT ≤1.5 x UNL and 
reduce dose by 1 dose level 
Grade 3 & 4 
Withdraw from study treatment. 
Hypersensitivity Grade 3 
No dose reduction. See Table 5 for management of 
hypersensitivity due to study drug. 
Withdraw from study treatment in case of 2nd grade 3 
episode. 
Grade 4 
Withdraw from study treatment. 
Dose reduction levels provided in Table 1. 
1 Maximum of 2 weeks delay, otherwise the patient will be withdrawn from study treatment. 
2 Including hearing disorders. 
 
4.4.2 Diarrhea 
 
No prophylaxis should be given; most of all, loperamide should not be prescribed 
prophylactically. Patients should stop any laxative treatment and avoid food and beverage, which 
might accelerate intestinal transit. 
Diarrhea can be life threatening and may lead to dehydration, electrolyte imbalance, or sepsis. 
Diarrhea should be treated promptly with loperamide. Patients with diarrhea should be carefully 
monitored, especially patients with previous external radiation therapy, and should be given fluid 
and electrolyte replacement if they become dehydrated. Loperamide should be given to patients 
when they leave hospital. 
Diarrhea ≥ Grade 3 in the absence of neutropenia ≥Grade 3: 
In addition to the general precautions and prompt treatment with loperamide, patients should be 
given antibiotic support if they develop ileus, fever or neutropenic complications. Subsequent 
chemotherapy treatments should be delayed in patients until return of pretreatment bowel 
function for at least 24 hours without need for anti-diarrheal medication. Subsequent doses of 
study drug should be decreased by 1 dose level according to Table 3. 
Diarrhea ≥Grade 3 associated with neutropenia ≥Grade 3: 
In addition to prompt treatment with loperamide and fluid and electrolyte replacement, 
aggressive treatment with antibiotic support is recommended. Complete blood count (CBC) 
should be assessed every 3 days [-1/+0] until ANC resolves to ≥1500/μL. Subsequent 
chemotherapy treatments should be delayed in such patients for up to 2 weeks until return of 
pretreatment bowel function for at least 24 hours without need for anti-diarrheal medication and 
until ANC resolves to ≥1.5 x 109/L. Following recovery, the dose of study drug should be 
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4.4.3 Other Toxicities 
 
For grade ≥3 toxicities except fatigue, local reaction, fluid retention, anemia and other toxicities 
that merely are uncomfortable but do not cause serious morbidity to patients, cabazitaxel should 
be held for a maximum of 2 weeks from the planned date of reinfusion until resolution to 
grade ≤1, then reinstituted, if medically appropriate. A dose reduction of subsequent doses will 
be left to the investigator’s judgment. These patients will be withdrawn from study treatment if 
>1 dose reduction is needed. Any measures such as frozen gloves or socks or scalp cooling cap 
to prevent nail toxicity or alopecia are left to the investigator judgment. 
 
Table 4: Intervention for hypersensitivity 
Symptom and Severity 
Intervention Recommendation 
Mild symptoms: 
localized cutaneous reaction 
such as mild pruritus, flushing, 
rash. 
 
• Consider decreasing the rate of infusion until 
recovery of symptoms, stay at bedside 
• Then, complete study drug infusion at the initial 
planned rate 
Moderate symptoms: 
any symptom such as 
generalized pruritus, flushing, 
rash, dyspnea, back pain during 
infusion, hypotension with 
systolic blood pressure (BP) 
>80 mm Hg not listed above 
(mild symptoms) or below 
(severe symptoms). 
• Stop study drug infusion, 
• Give diphenhydramine 50 mg i.v. and/or i.v. 
dexamethasone 10 mg, 
• Resume study drug infusion within 3 hours 
following recovery of hypersensitivity reaction. 
Administer study drug over 2 hours for all 
subsequent treatments. 
Severe symptoms, such as:  
bronchospasm, generalized 
urticaria, systolic BP ≤80 mm 
Hg, angioedema. 
 
• Stop study drug infusion; 
• Give IV diphenhydramine 50 mg and/or i.v. 
dexamethasone 10 mg and/or epinephrine as 
needed. 
• Severe hypersensitivity reactions require 
immediate discontinuation of the cabazitaxel 
infusion and administration of appropriate therapy. 
 
Anaphylaxis (Grade 4 reaction) 
Withdraw from study treatment. 
 
 
 
 
 
 
 

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Management of subsequent cycles 
The recommended pretreatment for subsequent infusions is 50 mg diphenhydramine i.v. or other 
i.v. H1 antihistaminic agent and 10 mg dexamethasone i.v. 30 minutes prior to study drug 
infusion. For patients who experience moderate or severe hypersensitivity reactions, the study 
drug should be administered over 2 hours for subsequent treatment courses in addition to 
premedication as noted above. These patients must be informed of the potential risk of recurrent 
allergic reactions and must be carefully monitored. 
If the initial reaction is grade 4 for allergy (anaphylaxis), the patient will receive no further 
treatment and will go off protocol therapy. 
If a second severe reaction (grade 3) recurs despite additional premedications as outlined above, 
the patient will go off protocol therapy. 
In case of late occurring hypersensitivity symptoms, e.g., appearance within 1 week after 
treatment of a localized or generalized pruritus, symptomatic treatment may be given (e.g., oral 
antihistamine), additional oral or i.v. premedication with antihistamine may also be given for the 
next cycle of treatment depending on the intensity of the reaction observed. No dose reductions 
will be made in any case. 
 
4.5 
Dose Modifications for Prednisone 
 
Prednisone can be discontinued for the onset or exacerbation of diabetes mellitus, hypertension, 
gastrointestinal ulceration or bleeding, severe neurological side effects, or other serious adverse 
events which the Investigator considers to be a contraindication to continuing steroids. 
Prednisone may be reinstituted with the resolution of the adverse events at the discretion of the 
Investigator.  The reason for altering the dose or discontinuing prednisone should be documented 
in the medical record.  
4.6 
Concomitant Medications 
 
Concomitant drugs that are strong CYP3A inducers or strong CYP3A inhibitors should be 
avoided. Concomitant administration of strong CYP3A inhibitors is expected to increase 
concentrations of cabazitaxel.  The concomitant administration of strong CYP3A inducers is 
expected to decrease cabazitaxel concentrations. If patients require co-administration of a strong 
CYP3A inhibitor, consider a 25% JEVTANA dose reduction.  
 
4.6.1 Permitted concomitant medications 
 
Prednisone will be prescribed to all patients receiving Cabazitaxel as per the local standard of 
care. The recommended dose is 5 mg given twice daily by mouth (or 10 mg once daily). Sites 
can adjust the dose per standard of care.    
All supportive care medications are permitted. It is encouraged that changes in bisphosphonate or 
denosumab usage to not occur during the study treatment on this protocol unless the deletion or 
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patient is not on a bisphosphonate or denosumab at study entry, bisphosphonates or denosumab 
should not be initiated during the study treatment so as not to confound adverse events or skeletal 
related events during the study treatment. If there is any change or initiation of bisphosphonate or 
denosumab usage during study treatment, the reason should be documented. 
In the event a patient requires therapeutic administration of G-CSF, the patient should receive 
this prophylactically in subsequent cycles. 
 
4.6.2 Prohibited concomitant medications 
 
Treatment with any other anticancer therapy except steroids is not allowed and is considered a 
protocol violation unless the patient has documented disease progression or has terminated 
further study treatment.  
Patients will be removed from study treatment for any cancer-related radiation therapy while on 
study treatment. Lesions which are symptomatic or cause unstable bone should be irradiated 
before the start of study treatment. Initiation of any radiotherapy after study treatment has begun 
will constitute disease progression. 
 
4.7 
Duration of Therapy 
In the absence of treatment delays due to adverse events, treatment may continue for 6 cycles or 
until:  
• Intercurrent illness that prevents further administration of treatment 
• Unacceptable adverse event(s) 
• Patient decides to withdraw from study 
• Requirement for treatment with a prohibited medication 
• Any seizure 
• Disease progression defined as:  
− 
Symptomatic progression: worsening of cancer-related symptoms mandating a 
change in anti-cancer therapy (radiation or chemotherapy) or ≥ 2 level decrease 
in ECOG PS 
 
 
AND/OR 
− 
Radiological progression: RECIST Criteria v1.1 for measurable disease or 
appearance of ≥ 2 new bone lesions on whole body bone scan confirmed on a 
subsequent scan 
 
 
AND/OR 
− 
PSA progression: After a minimum of 12 weeks of treatment, PSA increase ≥ 
25% (minimum ≥ 2 ng/mL) above baseline in patients without a PSA decline 
OR PSA increase that is ≥ 25% (minimum ≥ 2ng/ml) above nadir in patients 
with a PSA decline, confirmed by a second value ≥ 3 weeks later.  

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4.8 
Removal of Subjects from Study 
 
Patients can be taken off the study treatment and/or study at any time at their own request, or 
they may be withdrawn at the discretion of the investigator for safety, behavioral or 
administrative reasons. The reason(s) for discontinuation will be documented and may include: 
• Patient voluntarily withdraws from treatment (follow-up permitted);  
 
• Patient withdraws consent (termination of treatment and follow-up); 
 
• Patient is unable to comply with protocol requirements; 
 
• Patient demonstrates disease progression (unless continued treatment with study drug is 
deemed appropriate at the discretion of the investigator); 
 
• Patient experiences toxicity that makes continuation in the protocol unsafe; 
 
• Treating physician judges continuation on the study would not be in the patient’s best 
interest; 
 
• Lost to follow-up.  
 
Within six weeks of withdrawal, all study procedures outlined for the Progression/Off Treatment 
visit should be completed.  The primary reason for a patient’s withdrawal from the study is to be 
recorded in the source documents. 
 
If a patient does not return for a scheduled visit every effort should be made to contact the 
patient. In any circumstance, every effort should be made to document patient outcome and 
reason for withdrawal if possible. The investigator should request the patient return all unused 
product, request the subject return for a final visit if applicable, and follow with the subject 
regarding any unresolved adverse events. 
 
If the subject withdraws from the trial and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
 
If any patient should die during the study or within 28 days of stopping study treatment, the 
Investigator will inform the IRB and Sanofi.  The cause of death should be recorded in detail, 
within 24 hours, on a serious adverse event (SAE) form and reported to institutional, federal and 
any other appropriate committees. 
 
 

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4.9 
Duration of Follow Up 
 
Participants will be followed for 2 years after they are taken off protocol treatment or until death, 
whichever occurs first. Participants taken off protocol treatment for unacceptable adverse events 
will be followed until resolution or stabilization of the adverse event(s). 
 
5. 
DRUG INFORMATION 
 
5.1 
Cabazitaxel (Jevtana®) 
 
 
5.1.1 Formulation  
 
Cabazitaxel is supplied as a sterile, non-pyrogenic, non- aqueous yellowish to brownish yellow 
solution contained in a 15 mL clear glass vial, stoppered with a chlorobutyl rubber closure coated 
with a transparent ETFE coating. The rubberclosure is crimped to the vial with an aluminum cap 
covered with a light green plastic flip-off cap. Single-dose vial, containing a total of 60 mg of 
cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. The fill 
volume has been established to include an overfill, [i.e., 1.5 mL (nominal volume) + 0.33 mL]. 
This overfill was determined to ensure that a 10 mg/mL concentration is obtained in the premix 
and that 60 mg dose can be extracted. 
 
The diluent used for the preparation of the premix is a sterile, non-pyrogenic solution containing 
a 13% w/w ethanol solution in water for injection. This solution is contained in a 15 mL clear 
glass vial, stoppered with a chlorobutyl rubber closure coated with a transparent ETFE coating. 
The rubber closure is crimped to the vial with either an aluminum cap covered with a light grey 
plastic flip-off cap or a gold-color aluminum cap covered with a clear plastic flip-off cap. 
 
Each vial of diluent is overfilled to ensure that a 10 mg/mL concentration is obtained in the 
Premix and that 60 mg dose can be extracted. [ie, 4.5 mL (nominal volume) + 1.17 mL]. The 
solution is a clear colorless liquid. 
 
5.1.2 Supplier 
 
Cabazitaxel will be supplied by Sanofi at no cost to study patients.  
 
5.1.3 Storage Conditions 
 
Store between +15°C and +30°C. Do not refrigerate. The solvent was also shown to be stable 
under these conditions. All vials must be kept in their box until use. 
 
 
 
 

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5.1.4 Preparation and administration of cabazitaxel 
 
The preparation of the cabazitaxel infusion solution for administration requires the preparation of 
a premix solution at 60 mg/6 mL (nominal concentration).  This must be done with a 13% m/m 
ethanol solution in water for injection (the “diluent”) supplied with the cabazitaxel concentrate 
for solution for infusion (“preparation of the premix solution”).  Then the premix solution must 
be diluted in an infusion vehicle (“preparation of the infusion solution”) prior to administration. 
 
 
5.1.4.1 
Preparation of the premix solution under aseptic conditions (First Dilution) 
 
Set aside the required number of solvent vials (one solvent vial for each vial of cabazitaxel).  For 
each cabazitaxel vial: 
 
• Using a syringe fitted with a needle, withdraw the ENTIRE CONTENTS of the diluent 
vial and inject it into the corresponding vial of cabazitaxel. Direct the needle onto the 
inside wall of the cabazitaxel vial and inject slowly to limit foaming. 
 
• The addition of the ENTIRE CONTENTS of 1 diluent vial ensures a minimal extractable 
volume of the premix solution of 6 mL, containing 10 mg/mL of cabazitaxel. 
 
• Remove the syringe and needle and gently mix the reconstituted solution by repeated 
inversions for at least 45 seconds. Do not shake. 
 
• Allow the premix solution to stand for 5 minutes at room temperature to allow foam to 
dissipate. The solution is homogeneous and contains no visible particulate matter. It is 
normal for foam to persist after this time period. 
 
The premix solution contains 10 mg/mL of cabazitaxel. Then the premix solution must be diluted 
in an infusion vehicle so as to obtain the required dose for administration. The second dilution 
should be done immediately (within 30 minutes) to obtain the final infusion as detailed in 
5.1.4.2. 
 
5.1.4.2 
Preparation of the infusion solution under aseptic conditions (Second (Final) 
Dilution) 
 
WARNING: Since foam is normally present, the required dose must be accurately adjusted using 
a graduated syringe. 
 
• Aseptically, with a syringe and needle, withdraw the volume of the premix solution 
containing 10 mg/mL of cabazitaxel that corresponds to the required dose (mg) for 
administration of cabazitaxel 
 
• Inject the required premix volume into a r 250 mL infusion container 
(containing either 5% dextrose solution or 0.9% sodium chloride solution). If the 
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exceed the maximum concentration of 0.26 mg/mL. 
 
• Remove the syringe and thoroughly mix the final infusion solution by gently inverting 
the bag. The final infusion may crystallize over time—do not use and discard preparation 
if crystallization occurs.  
 
The concentration of the infusion should be between 0.10 mg/mL and 0.26 mg/mL (based on 
Maximum Tolerated Dose of 30 mg/m² and a Body Surface Area [BSA] of 2.1 m²). 
 
Mix the contents of the infusion container manually by gently inverting the bag or bottle. 
 
 
5.1.4.3 
Storage period of premix and infusion solution  
 
The premix solution of cabazitaxel should be used immediately after preparation and within 
1 hour at ambient temperature. 
 
The infusion solution is stable for 8 hours at ambient conditions (including the 1 hour infusion 
time) or a total of 24 hours under  refrigerated conditions, from preparation to end of infusion. 
 
 
5.1.4.4 
Risks and Precautions 
 
Neutropenic deaths have been reported with cabazitaxel. Frequent blood counts should be 
obtained to determine if initiation of G-CSF and/or dose modifications should be considered. 
Weekly blood counts are essential during Cycle 1 and before each treatment cycle. Cabazitaxel 
should not be administered to patients with a neutrophil count ≤1500 cells/mm3.  Use caution in 
patients with hemoglobin < 10 g/dL. Primary prophylaxis with G-CSF should be considered in 
patients with high-risk clinical features (age > 65 years, poor performance status, previous 
episodes of febrile neutropenia, extensive prior radiation ports, poor nutritional status, or other 
serious comorbidities) that predispose them to increased complications from prolonged 
neutropenia. Therapeutic use of G-CSF and secondary prophylaxis should be considered in all 
patients considered to be at increased risk for neutropenia complications. 
 
Hypersensitivity reactions may occur within a few minutes following the initiation of the 
infusion of cabazitaxel, thus facilities and equipment for the treatment of hypotension and 
bronchospasm should be available.  Severe hypersensitivity can occur, especially during the first 
two infusions, and may include rash, erythema, hypotension, and bronchospasm. For a severe 
hypersensitivity reaction, cabazitaxel should be discontinued immediately and appropriate 
therapy administered. Cabazitaxel is contraindicated in patients with a past history of severe 
hypersensitivity to cabazitaxel or drugs formulated with polysorbate 80 (e.g., docetaxel). 
 
Death related to diarrhea and subsequent electrolyte imbalance has been reported. Dosage should 
be modified with grade 3 or 4 diarrhea. Nausea and vomiting are also common. Patients should 
be rehydrated and treated with antiemetics and antidiarrheals as needed.  
 
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closely. 
 
Patients with impaired hepatic function are excluded as it is likely to increase cabazitaxel 
concentrations.  
 
Patients  ≥ 65 years old should be monitored closely as they are more likely to experience fatal 
outcomes, especially secondary to neutropenia.  
 
Other toxicities include (all grades):  
 
- 
Blood and lymphatics: neutropenia (94%); febrile neutropenia (7%); anemia (98%); 
leukopenia (96%), and thrombocytopenia (48%) 
 
- 
Cardiac: arrhythmias (including atrial fibrillation/flutter, tachycardia, complete 
arteriovenous [AV] block, bradycardia, and supraventricular tachycardia [SVT]) (5%) 
 
- 
Gastrointestinal: diarrhea (47%); nausea (34%); vomiting (22%); constipation (20%); 
abdominal pain (17%); dyspepsia/reflux (10%) 
 
- 
General disorders: fatigue (37%); asthenia (20%); pyrexia (12%); peripheral edema (9%); 
mucositis (6%); pain (5%) 
 
- 
Infections: urinary tract infection (8%) 
 
- 
Nutrition: anorexia (16%); dehydration (5%); decreased weight (9%) 
 
- 
Musculoskeletal: back pain (16%); arthralgia (11%); muscle spasms (7%) 
 
- 
Nervous system: peripheral neuropathy (sensory and motor) (13%); dysgeusia (11%); 
dizziness (8%); headache (8%) 
 
- 
Urinary tract: hematuria (17%); dysuria (7%) 
 
- 
Respiratory: dyspnea (12%); cough (11%) 
 
- 
Dermatologic: alopecia (10%) 
 
- 
Vascular: Hypotension (5%) 
 
 
5.2 
Prednisone 
 
Prednisone is a corticosteroid used for the treatment of many cancers and is usually given along 
with other anticancer drugs. In this protocol it will be administered orally at a dose of 10 mg per 
day. 
 
 

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5.2.1 Formulation  
 
For prednisone, refer to the package insert or summary of product characteristics of details on 
description, administration, and precautions for use.  
 
5.2.2 Supplier 
 
Prednisone is commercially available in 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg tablets.  
 
5.2.3 Storage condition  
 
Store away from heat, light, and moisture at room temperature. 
 
5.2.4 Risks and Precautions 
 
 
Prednisone should be administered with fluids and food to decrease the risk of gastrointestinal 
complications. Prednisone can exacerbate diabetes mellitus, hypertension, and chronic and acute 
infections. Prednisone can mask symptoms of infections. 
 
Other toxicities include:  
 
- 
Cardiovascular: fluid retention (common), hypertension, congestive heart failure 
 
- 
Gastrointestinal (GI): pain and/or ulcerations anywhere in the GI tract (common), weight 
increase (common), increased thirst, pancreatitis (rare) 
 
- 
Infections: increased risk of acute and chronic infections (common) 
 
- 
Metabolic: diabetes mellitus, fluid and electrolyte disturbances 
 
- 
Musculoskeletal: weakness (common), decrease in muscle mass (common), osteoporosis 
 
- 
Neurological: mood swings (common), depression, insomnia (common), dizziness, 
headache, confusion (rare), excitement (rare), psychosis (rare), seizures (rare) 
 
- 
Ophthalmological: visual changes 
 
- 
Urological: increased frequency of urination 
 
Withdrawal of prednisone after prolonged therapy may result in symptoms such as fever, 
myalgias, and arthralgia, which could be symptoms of adrenal insufficiency. 
 
 

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6. 
ASSESSMENT OF EFFECTS 
 
6.1 
Safety assessment  
 
The adverse effects of the drug will be assessed from adverse events, vital signs and by clinically 
significant changes in the laboratory evaluations and ECGs. Adverse events (AE) will use the 
descriptions and grading scales found in the revised NCI Common Terminology Criteria for 
Adverse Events (CTCAE). This study will utilize the CTCAE Version 4.03 for adverse event 
reporting.  
 
 
6.2 
Efficacy assessments  
 
All efficacy assessments will be assessed from the time of registration.  
 
6.2.1 Radiological Response 
 
Subjects that have measurable disease at screening will be evaluated for response on the basis of 
RECIST criteria v1.1. Tumor measurements using physical examination, spiral CT scan and/or 
MRI or other appropriate techniques deemed suitable by the investigator will be performed at 
screening within 28 days of subject registration and repeated at the end of Cycle 2 (6 weeks), end 
of Cycle 4 (12 weeks), then every 12 weeks. In case of partial or complete response, tumor 
measurements will be repeated after at least 6 weeks for confirmation.  
 
6.2.2 PSA response 
 
 
The PSA response criteria will be defined as per modified PSA Working Group Criteria2. 
 
Response: Definition of response: ≥50% decline in PSA from baseline maintained for at least 3 
weeks and measured by the same laboratory, and without evidence of other disease progression 
documented at time of confirmatory values.  PSA response duration will commence on the date 
of the first 50% decline in PSA. 
 
Non Response: Failure to achieve PSA response or progression criteria. 
 
Progression: 
Patients without a PSA decline: PSA increase ≥ 25% (minimum ≥ 2 ng/mL) above baseline after 
minimum of 12 weeks on treatment, confirmed by a second value ≥ 3 weeks later. 
• 
Patients with a PSA decline: PSA increase ≥ 25% (minimum ≥ 2ng/mL) above nadir 
in patients, confirmed by a second value ≥ 3 weeks later. 
 
 
                                                 
2  
Bubley, GJ, et al., Eligibility and response guidelines for phase II clinical trials in androgen-
independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin 
Oncol, 1999. 17(11): p. 3461-7. 

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Clinical Benefit 
Patients are considered to have had a clinical benefit if they experience a PSA or measurable 
radiological response of any duration or stable disease for ≥ 12 weeks (no symptomatic 
progression, PSA progression, or objective disease progression). 
 
Disease Progression 
Disease Progression is defined as the development of symptomatic or radiological progression at 
any time or PSA progression after 12 weeks [i.e. PSA progression alone prior to 12 weeks does 
not constitute progressive disease]. Progression will be classified as any of the following: 
a. Symptomatic progression: worsening of cancer-related symptoms mandating a change 
in anti-cancer therapy (radiation or chemotherapy) or ≥ 2 level decrease in ECOG PS. 
b. Radiological progression: RECIST criteria v1.1 for measurable disease or appearance 
of ≥ 2 new bone lesions on whole body bone scan confirmed on a subsequent scan. 
c. PSA progression: After a minimum of 12 weeks of treatment, PSA increase ≥ 25% 
(minimum ≥ 2 ng/mL) above baseline after minimum of 12 weeks on treatment in 
patients without a PSA decline OR PSA increase that is ≥ 25% (minimum ≥ 2ng/ml) 
above nadir in patients with a PSA decline, confirmed by a second value ≥ 3 weeks 
later. 
 
 
7. 
STUDY CALENDAR 
 
Pre-study evaluations are to be conducted within 14 days prior to registration.  Scans must be 
done <28 days prior to registration.  In the event that the patient’s condition is deteriorating, 
laboratory evaluations should be repeated within 48 hours of the next cycle of therapy. 
All assessments must be performed prior to administration of any study medication. All 
study assessments and medications should be administered within the 28 day screening 
period as indicated in section 4.0.  

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Evaluation 
Pre-
Treatment 
 
Pre-
Treatment 
Day 1 
of each 
Cycle8 
End of Cycle 
2, 4, then 
every 12 
weeks 
End of 
Treatment10 
Safety Visit 
(28 days after 
taken off protocol 
treatment) 
Follow Up 
(Every 3 months 
from time of Off 
Treatment)12 
Window 
-28 to -1 
day 
-14 to -1 
day 
± 3 days 
± 4 days 
± 4 days 
± 4 days 
± 7 days 
Medical History 
X 
 
 
 
 
 
 
*Physical Exam including: height6, weight, 
BSA7, performance status11, clinical tumor 
measurements (if applicable) 
 
X 
X 
 
 
X 
X9 
Vital signs5 
 
X 
X 
 
 
X 
X9 
Hematology: CBC, differential 
 
X 
X14 
 
 
X 
 
Biochemistry: creatinine (serum), sodium, 
potassium, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, GGT, albumin 
 
X 
X 
 
 
X 
 
Testosterone (total) 
X1 
 
 
X 
X 
 
 
PSA 
 
X 
X 
 
X 
 
 
Urine test 
 
X 
 
 
 
 
 
ECG 
 
X 
 
 
X 
 
 
Chest/abdomen/pelvis CT scan (MRI if 
appropriate) 
X1 
 
 
X2 
X 
 
X2 
Whole body Bone scan 
X1 
 
 
X2 
X 
 
X2 
Correlative Samples: Plasma, Serum, Whole 
Blood  
 
X 
 
X3 
X 
 
 
Archival Tumor Tissue 
 
X 
 
 
 
 
 
Oral corticosteroids prior to cabazitaxel 
infusion  
 
 
X 
 
 
 
 
Cabazitaxel infusion 
 
 
X 
 
 
 
 
Prednisone  
 
 
 
 
 
 
Adverse events and Concomitant Medications 
X4 
 
Continuously 
 

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Evaluation 
Pre-
Treatment 
 
Pre-
Treatment 
Day 1 
of each 
Cycle8 
End of Cycle 
2, 4, then 
every 12 
weeks 
End of 
Treatment10 
Safety Visit 
(28 days after 
taken off protocol 
treatment) 
Follow Up 
(Every 3 months 
from time of Off 
Treatment)12 
*Complete physical examination at screening only; subsequent physical examinations are limited to signs and symptoms of disease or toxicity.  
1. Within 28 days of registration. 
2. Radiology to be repeated at the end of Cycle 2 (6 weeks), Cycle 4 (12 weeks), then every 12 weeks. Patients that go off treatment without radiological 
progression will have scans repeated every 3 months until documented disease progression. 
3. At Baseline, end of Cycle 4, and End of Treatment 
4. Baseline symptoms will be documented prior to starting study treatment. Adverse Events collection will begin from the time of first dosing. Adverse events 
will be coded as per CTCAE v4.03. 
5. Vitals: temperature, systolic and diastolic blood pressure, respiratory rate, and pulse. 
6. Height is required at Baseline only. 
7. BSA should be calculated prior to each dose of chemotherapy. 
8. One cycle consists of 3 weeks. 
9. Survival status only. 
10. End of treatment is at the time the decision is made to take the patient off study treatment.  
11. ECOG only. 
12. All patients will be followed to death or for a maximum of 2 years. 
13. Weekly CBC and differential is required during Cycle 1  
 
 
 
 
 

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8. 
CORRELATIVE/SPECIAL STUDIES 
 
Correlative samples will be collected at Baseline, at the end of Cycle 4 and at the end of 
treatment. The correlative samples are mandatory. 
 
The correlative samples consist of: Tumor tissue from the time of diagnosis or the most recent 
biopsy (prior to the initiation of study treatment), serum, and plasma/buffy specimens for 
molecular markers or signature predictive of cabazitaxel benefit (to include status of AR 
pathway, androgen biosynthetic pathway genes, ABCB1, MRP1, and other mediators of taxane 
resistance, among others. 
 
Tumor Sample Guidelines:  Tumor specimens from the diagnostic biopsy or the most recent 
biopsy (prior to the initiation of study treatment) should be submitted for banking along with a 
completed specimen submission form and a copy of the corresponding pathology report.  
 
Please submit 1 H&E stained slide (with the location of the tumor circled by pathology) along with 
10-15 unstained slides.  Slides should be cut at ~5 microns and mounted on positively charged (+) 
slides.  Ship specimens to UC Davis according to the instructions provided in the appendix. 
  
Blood Sample Collection Guidelines 
With the patient's consent, serial serum and plasma/buffy specimens will be collected within 28 
days prior to study treatment, at the conclusion of cycle 4 (+/- 10 days) and at the conclusion of 
treatment (+/-10 days). Blood samples will be collected using standard venipuncture techniques. 
A total of 20 mL of whole blood will be drawn at each time point. 
 
Serum Collection: Whole blood will be collected in 10 mL red top vacutainer tubes (BD 
Vacutainer #367820) and allowed to clot for 45-60 minutes. Serum will be separated from cells 
within 60-90 minutes of venipuncture. Serum is separated from clotted blood by centrifugation at 
1800 x g for ten minutes. Using a pipette, serum will then equally aliquoted into .5 mL aliquots 
(up to eight cryovials).  All cryovials should then be frozen as rapidly as possible and stored in a 
-70°C or colder freezer until shipping to UC Davis according to the instructions provided in the 
appendix. 
 
Plasma/Buffy Collection:  Whole blood will be collected in 10 mL purple top EDTA tubes (BD 
Vacutainer #366643).  Tube should be centrifuged as soon as possible at approximately 800 x g 
for 10 minutes.  Plasma should be transferred to a 15 mL conical tube and centrifuged a second 
time at 1000 – 1500 x g for 10 minutes.  After the second centrifugations, aliquot plasma equally 
into 0.5 mL aliquots (up to eight cryovials).  The buffy coat, a whitish layer of cells between the 
plasma and the red blood cell layers, should be collected from the original purple top tube and 
split into two labeled cryovials. All cryovials should then be frozen as rapidly as possible and 
stored in a -70°C or colder freezer until shipping to UC Davis.   
  
Samples will be collected at the following time points (+/- window): 
• Within 28 days prior to study treatment. 
• At the conclusion of cycle 4 (+/-10 days). 
• At the conclusion of treatment (+/- 10 days). 

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Specimen Banking 
 
Patient samples collected for this study will be retained at UC Davis. Specimens will be stored 
indefinitely or until they are used up. If future use is denied or withdrawn by the patient, best 
efforts will be made to stop any additional studies and to destroy the specimens. 
 
The Sponsor-Investigator,  Christopher Evans, MD, will be responsible for reviewing and 
approving requests for clinical specimen from potential research collaborators outside of  UC 
Davis. Collaborators will be required to complete an agreement (a Material Transfer Agreement 
or recharge agreement) that states specimens will only be released for use in disclosed research. 
Any data obtained from the use of clinical specimen will be the property of  UC Davis for 
publication and any licensing agreement will be strictly adhered to.  
 
The specimens, DNA, and their derivatives may have significant therapeutic or commercial 
value. The Informed Consent form contains this information and informs the subject that there is 
the potential for financial gain by UC Davis, the investigator or a collaborating researcher or 
entity.  
 
The following information obtained from the subject's medical record may be provided to 
research collaborators when specimens are made available:  
• Diagnosis  
• Collection time in relation to study treatment 
• Clinical outcome – if available 
• Demographic data 
 
 
9. 
SAFETY AND REPORTING REQUIREMENTS 
 
9.1 
Adverse Event Definition 
 
Adverse event (AE) means any untoward medical occurrence in a patient or subject administered 
a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal 
relationship with this treatment.  An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product whether or not it is related to the medicinal product.  
This includes any newly occurring event, or a previous condition that has increased in severity or 
frequency since the administration of study drug. 
 
For this protocol an abnormal laboratory value will not be assessed as an AE unless that value 
leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is 
considered by the investigator to be a clinically significant change from baseline.  
 
Any other AE not listed as an expected event in the Investigator’s Brochure or in this protocol 
will be considered unexpected. 
 

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9.2 
Adverse Event Documentation 
 
Any patient enrolled in the trial who signed the consent form and received at least one dose of 
cabazitaxel will be eligible for adverse event reporting. Adverse events will use the descriptions 
and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events 
(CTCAE). This study will utilize the CTCAE Version 4.03 for adverse event reporting.  
 
All AEs must be recorded on case report forms (CRFs). Documentation must be supported by an 
entry in the subject’s file. Each event should be described in detail along with start and stop 
dates, severity, relationship to investigational product as judged by the Investigator, action taken 
and outcome. 
 
9.3 
Severity of Adverse Events 
 
The severity of an AE is graded as follows: 
 
Mild (grade 1): the event causes discomfort without disruption of normal daily activities. 
 
Moderate (grade 2): the event causes discomfort that affects normal daily activities. 
 
Severe (grade 3): the event makes the patient unable to perform normal daily activities or 
significantly affects his/her clinical status. 
 
Life-threatening (grade 4): the patient was at risk of death at the time of the event. 
 
Fatal (grade 5): the event caused death. 
 
 
9.4 
Serious Adverse Event Definition 
 
Serious adverse event (SAE) means any untoward medical occurrence that at any dose: 
 
• Results in death. 
• Is life-threatening (Note: the term “life-threatening” refers to an event/reaction in which 
the patient was at risk of death at the time of the event/reaction.  It does not refer to an 
event/reaction which hypothetically might have caused death if it were more severe). 
• Requires inpatient hospitalization or prolongation of an existing hospitalization  
• Results in persistent or significant disability or incapacity.  (Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions). 
• Is a congenital anomaly/birth defect. 
• Is a medically important event or reaction.  Medical and scientific judgment should be 
exercised in deciding whether other situations should be considered serious, such as 
important medical events that might not be immediately life-threatening or result in death 
or hospitalization, but might jeopardize the patient or might require intervention to 
prevent one of the other outcomes listed in the definition above. 
 

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Clarification should be made between the terms serious and severe because they ARE NOT the 
same.  The term severe is often used to describe the intensity (severity) of a specific event (as in 
mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively 
minor medical significance (such as a severe headache).  This is NOT the same as serious, which 
is based on patient/event outcome or action criteria described above and is usually associated 
with events that pose a threat to a patient’s life or functioning.  A severe AE does not necessarily 
need to be considered serious.  For example, persistent nausea of several hours duration may be 
considered severe nausea but may not be considered an SAE.  On the other hand, a stroke 
resulting in only a minor degree of disability may be considered mild but would be defined as an 
SAE based on the above noted criteria.  Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
 
9.5 
Procedures for Reporting Serious Adverse Events (SAEs)  
 
9.5.1 Safety Reporting Requirements for IND Exempt Studies 
 
For Investigator Sponsored IND Exempt Studies there are some reporting requirements for the 
FDA in accordance with the guidance set forth in 21 CFR 314.80. 
 
Post-marketing 15-Day ‘Alert Report’ 
 
The Sponsor-Investigator is required to notify the FDA of each adverse drug experience that is 
both serious and unexpected and is assessed by the investigator to be possibly related to study 
treatment as soon as possible but in no case later than 15 calendar days of initial receipt of the 
information.  An unexpected adverse event is one that is not already described in the Investigator 
Brochure.  Such reports (2 copies) are to be submitted to the FDA at the following address: 
Central Document Room, 5901-B Ammendale Rd., Beltsville, MD 20705-1266. 
All 15-Day Alert Reports submitted to the FDA by the Sponsor-Investigator must also be faxed 
to Sanofi.  
 
9.5.2 Responsibility for Reporting Serious Adverse Events to Sanofi 
 
Report SAEs (initial and follow up), including pregnancy and overdose to Sanofi 
Pharmacovigilance using the MedWatch 3500A form.  The SAE from must be faxed to Sanofi 
within 1 working day of awareness of the SAE. The foregoing is applicable to all SAEs, 
irrespective of causality.  
 
Sanofi Group Entity Pharmacovigilance Contact: 
 
IST/ISS Investigators will notify Sanofi via fax or email, attention Sanofi Pharmacovigilance 
(PV): 
 
Fax: 908-203-7783   
 
E-mail:  USPVmailbox@sanofi-aventis.com 
 

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9.5.3 Reporting to the Institutional Review Board 
 
Both serious and non-serious adverse events will be reported in accordance with UCD IRB 
Administration and UCD Cancer Center Office of Clinical Research (OCR) policies.  The UC 
Davis IRB can be reached at (916) 703-9151.  
 
Participating site(s) will report adverse events per institution’s IRB guidelines.  
 
9.5.4 Follow up of Adverse Events and Serious Adverse Events 
 
For the SAEs that have been deemed by the investigator as unrelated to protocol treatment, the 
SAE reporting period begins after the first dosing and ends on the date of scheduled Safety Visit 
(4 weeks follow-up visit) or 28 days after discontinuation of the study drug, whichever is later.  
For the SAEs that have been deemed by the investigator as at least possibly related to protocol 
treatment, the SAE must be reported even if this occurs after the date of scheduled Safety Visit 
(4 weeks follow-up visit) or 28 days after discontinuation of the study drug.   
 
The investigator shall provide follow-up information as and when available in a new follow-up 
SAE form. All SAEs must be followed until resolved, become chronic, or stable unless the 
subject is lost to follow up. Resolution status of such an event should be documented on the 
CRF.  
 
The CRF should capture all AEs occurring from cycle 1 day 1 till the date of scheduled Safety 
Visit (4 weeks follow-up visit) or 28 days after discontinuation of the study drug, whichever is 
later.  
 
In addition, any known untoward event of any severity that occurs subsequent to the AE 
reporting period that the Investigator assesses as at least possibly related to the study therapy 
(i.e., the relationship cannot be ruled out) should also be reported as an AE. 
 
Suggested Reporting Form: 
 
• SAE Report Form  
• US FDA MedWatch 3500A:  
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm 
• Any other form deemed appropriate by the sponsor-investigator 
 
 
Medwatch 3500A Reporting Guidelines: 
In addition to completing appropriate demographic and suspect medication information, the 
report should include the following information within the Event Description of the MedWatch 
Form 3500A: 
• Treatment regimen (dosing, frequency, combination therapy) 
• Protocol description (include number if assigned) 
• Description of event, severity, treatment, and outcome, if known 
• Supportive diagnostic and laboratory results 

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• Investigator’s assessment of the relationship of the SAE to each investigational product 
and suspect medication 
 
Follow-up information 
Additional information may be added to a previously submitted report by any of the following 
methods: 
• Adding to the original MedWatch Form 3500A and submitting it as follow-up 
• Adding supplementary summary information and submitting it as follow-up with the 
original MedWatch Form 3500A 
• Summarizing new information and faxing it with a cover letter including subject 
identifiers (ie, DOB, initials, subject number), protocol description and number, suspect 
drug, brief adverse event description, and notation that additional or follow-up 
information is being submitted 
 
9.5.5 Reporting to the Institutional Review Board 
 
Both serious and non-serious adverse events will be reported in accordance with UCD IRB 
Administration and UCD Cancer Center Office of Clinical Research (OCR) policies.  The UC 
Davis IRB can be reached at (916) 703-9151.  
 
Participating site(s) will report adverse events per institution’s IRB guidelines.  
 
 
10. 
STATISTICAL CONSIDERATIONS 
 
10.1 
Study Design and Overview of Primary and Secondary Endpoints 
 
This is a phase II, single-arm, open-label study.  
 
The proposed primary endpoint for this single arm trial is PSA response (defined as >= 50% 
reduction from baseline). 
 
Secondary endpoints include safety, radiologic response as assessed by RECIST, progression 
free survival, overall survival, and biomarkers for prostate cancer.   
 
10.2 
Sample Size Estimation /Accrual Rate 
 
Forty-five patients will be enrolled, of whom we estimate 37 will be evaluable for efficacy. We 
anticipate accruing 4 patients per month. 
 
In a retrospective analysis of response to various hormonal therapies (including abiraterone or 
enzalutamide) in patients who had a suboptimal response to prior ADT, defined as duration of 
ADT benefit <= 16 months (Loriot, ASCO GU 2012), PSA response ( >= 50% reduction from 
baseline) was seen in only 18% of patients. In contrast, patients with ADT benefit lasting > 16 
months had a PSA response of 58% with these same hormonal therapies.  
 

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The proposed primary endpoint for this single arm trial is PSA response rate (defined as >= 50% 
reduction from baseline). Assuming that historical response rate is approximately 20%, we 
anticipate that cabazitaxel will increase this rate to at least 45% or higher. The response rate will 
be compared to a historical response rate of 20% using the exact binomial test for a single 
proportion.  With 37 subjects, the exact binomial test will have approximately 90% power to 
detect a difference from the historical response rate if the probability of response with 
cabazitaxel is 0.45.   
 
 
10.3 
Evaluation of Efficacy 
 
 
The efficacy analysis population will consist of patients who receive any amount of study drug.  
PSA response rate will be compared to a historical response rate of 20% using the exact binomial 
test for a single proportion.  For all binary outcomes (PSA response rate and RECIST response 
rate), confidence intervals for the response rate will be calculated using Wilson’s method (1927). 
 
Patients with insufficient follow up to be evaluated for PSA and RECIST response will be 
excluded from primary analysis of these endpoints; however, a sensitivity analysis will be 
conducted in which these patients are assumed to have progressive disease.   
 
Medians of time-to-event outcomes will be estimated using the method of Kaplan and Meier, 
with confidence intervals estimated using Greenwood’s method.  For analysis of time-to-event 
outcomes, patients missing all PSA and RECIST assessments will be censored at the date of 
registration plus one day.  
 
Continuous or ordered biomarkers will be compared between PSA responders and non-
responders using the Wilcoxon rank sum test, and categorical biomarkers will be compared 
between PSA responders and non-responders using Fisher’s Exact Test. 
 
 
10.4 
Evaluation of Safety 
  
The safety analysis population will consist of patients who received any amount of study drug.  
Clinical and laboratory adverse events will be summarized by coded term and severity.  
Laboratory values will be plotted over time. 
 
 
11. 
ADMINISTRATIVE REQUIREMENTS 
 
11.1 
Good Clinical Practice 
 
The study will be conducted in accordance with the International Conference on Harmonisation 
(ICH) for Good Clinical Practice (GCP) and the appropriate regulatory requirement(s).  The 
investigator will be thoroughly familiar with the appropriate use of the drug as described in the 
protocol and Investigator’s Brochure.  Essential clinical documents will be maintained to 

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demonstrate the validity of the study and the integrity of the data collected.  Master files should 
be established at the beginning of the study, maintained for the duration of the study and retained 
according to the appropriate regulations. 
 
 
11.2 
Ethical Considerations 
 
The study will be conducted in accordance with ethical principles founded in the Declaration of 
Helsinki.  The IRB will review all appropriate study documentation in order to safeguard the 
rights, safety and well-being of the patients.  The study will only be conducted at sites where 
IRB approval has been obtained.  The protocol, Investigator’s Brochure, informed consent, 
advertisements (if applicable), written information given to the patients, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB by the 
investigator.  Sanofi requests that informed consent documents be reviewed by Sanofi or 
designee prior to IRB submission. 
 
11.3 
Required Documentation  
 
Before the study can be initiated at any site, the following documentation must be provided to 
the OCR. 
 
• 
A copy of the official IRB approval letter for the protocol and informed consent 
• 
IRB membership list 
• 
CVs and medical licensure for the principal investigator and any associate investigators 
who will be involved in the study 
• 
Form FDA 1572 appropriately filled out and signed with appropriate documentation  
• 
A copy of the IRB-approved consent form 
• 
CAP and CLIA Laboratory certification numbers and institution lab normal values 
• 
Executed clinical research contract 
 
 
11.4 
Study Registration 
 
Once signed, informed consent has been obtained and all pretreatment evaluations have been 
performed, patients will be entered on study according to UCD Office of Clinical Research 
(OCR) policy. To register a patient, the data manager or designee must complete the Eligibility 
Checklist and the Patient Registration Form.  A patient accession number will then be assigned.  
Administration of study drug may not be initiated until the patient is registered.  See 14.6 for 
Multicenter Guidelines.  
 
11.5 
Patient Information and Informed Consent 
 
After the study has been fully explained, written informed consent will be obtained from either 
the patient or his guardian or legal representative prior to study participation.  The method of 
obtaining and documenting the informed consent and the contents of the consent will comply 
with ICH-GCP and all applicable regulatory requirement(s).  In accordance with UCD OCR 

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policy an original signed and dated participant Informed Consent document will reside in a 
secured location within the UCD OCR.  Copies of the signed and dated Informed Consent 
document will be provided to the study participant and UCD Health System Information 
Management for inclusion in the participant’s UCD Health System Medical Record or per 
participating site’s policies. 
 
11.6 
Protocol Deviations 
 
All protocol deviations will be reported in accordance with UCD IRB Administration and UCD 
Cancer Center OCR policies or the participating site’s IRB policies. 
 
11.7 
Patient Confidentiality 
 
In order to maintain patient privacy, all study reports and communications will identify the 
patient by initials and the assigned patient number.  Data capture records and drug accountability 
records will be stored in secure cabinets in the UCD OCR or at the participating institutions.  
Medical records of patients will be maintained in strict confidence according to legal 
requirements.  The investigator will grant monitor(s) and auditor(s) from Sanofi or its designees 
and regulatory authority(ies) access to the patient’s original medical records for verification of 
data gathered on the data capture records and to audit the data collection process.  The patient’s 
confidentiality will be maintained and will not be made publicly available to the extent permitted 
by the applicable laws and regulations. 
11.8 
Protocol Compliance 
 
The investigator will conduct the study in compliance with the protocol given approval/favorable 
opinion by the IRB and the appropriate regulatory authority(ies).  Changes to the protocol will 
require approval from Sanofi and written IRB approval/favorable opinion prior to 
implementation, except when the modification is needed to eliminate an immediate hazard(s) to 
patients.  The IRB may provide, if applicable regulatory authority(ies) permit, expedited review 
and approval/favorable opinion for minor change(s) in ongoing studies that have the approval 
/favorable opinion of the IRB.  The investigator will submit all protocol modifications to Sanofi 
and the regulatory authority(ies) in accordance with the governing regulations.  
Any departures from the protocol must be fully documented in the source documents.   
 
11.9 
On-site Audits 
 
Regulatory authorities, the IRB and/or Sanofi’s clinical quality assurance group may request 
access to all source documents, data capture records, and other study documentation for on-site 
audit or inspection.  Direct access to these documents must be guaranteed by the investigator, 
who must provide support at all times for these activities. 
 

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11.10 Drug Accountability and Disposal 
 
Accountability for the drug at all study sites is the responsibility of the principal investigator.  
The investigator will ensure that the drug is used only in accordance with this protocol.  Drug 
accountability records indicating the drug’s delivery date to the site (if applicable), inventory at 
the site (if applicable), use by each patient, and return to Sanofi’s or disposal of the drug 
according to institutional standard procedures (if applicable and if approved by Sanofi) will be 
maintained by the clinical site.  Accountability records will include dates, quantities, lot 
numbers, expiration dates (if applicable), and patient numbers.   
11.11 Premature Closure of the Study 
 
This study may be prematurely terminated, if in the opinion of the investigator or Sanofi, there is 
sufficient reasonable cause.  Written notification documenting the reason for study termination 
will be provided to the investigator or Sanofi by the terminating party.   
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to patients 
• Failure to enter patients at an acceptable rate 
• Insufficient adherence to protocol requirements 
• Insufficient complete and/or evaluable data 
• Plans to modify, suspend or discontinue the development of the drug 
 
11.12 Record Retention 
 
The investigator will maintain all study records according to ICH-GCP and applicable regulatory 
requirement(s).   
 
11.13  Quality Assurance and Control 
Quality assurance audits of select patients and source documents may be conducted by the UC 
Davis Comprehensive Cancer Center Quality Assurance Committee as outlined in the UC Davis 
Cancer Center Data and Safety Monitoring plan. 
Quality control will be maintained by the Quality Assurance team according to OCR policy. 
 
11.14  Data and Safety Monitoring 
In addition to the requirements for adverse event reporting as outlined in Section 6, this protocol 
is also subject to the UC Davis Cancer Center’s (UCDCC) Data and Safety Monitoring Plan. The 

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UCDCC is committed to pursuing high-quality patient-oriented clinical research and has 
established mechanisms to ensure both scientific rigor and patient safety in the conduct of 
clinical research studies. The UCDCC relies on a multi-tiered committee system that reviews and 
monitors all cancer clinical trials and ensures the safety of its participants, in compliance with 
institutional and federal requirements on adverse event (AE) reporting, verification of data 
accuracy, and adherence to protocol eligibility requirements, treatment guidelines, and related 
matters. The Scientific Review Committee (SRC) assumes overall oversight of cancer studies, 
with assistance and input from two independent, but interacting, committees: the Quality 
Assurance Committee and the Data Safety Monitoring Committee. A multi-level review system 
strengthens the ability of the UCDCC to fulfill its mission in conducting high quality clinical 
cancer research. 
As per University of California Davis Cancer Center (UCDCC) Office of Clinical Research 
(OCR) SOP AM 506: Protocol Specific Meetings, the principal investigator (PI) and clinical 
research coordinator (CRC) meet at least monthly for ongoing study information, to discuss 
patient data and adverse events and to determine if dose escalation is warranted, when applicable 
According to the UCDCC Data and Safety Monitoring Plan (DSMP), any new serious adverse 
events related to the drugs being used on this trial are reviewed monthly by the UCDCC Data 
and Safety Monitoring Committee (DSMC) and any applicable changes to the study are 
recommended to the PI, if necessary. 
The UCDCC Scientific Review Committee (SRC) determines if a UCDCC Data and Safety 
Monitoring Board (DSMB) is required.  If required, the DSMC will appoint a DSMB. The 
DSMB is responsible for reviewing study accrual logs, adverse event information and dose 
escalation meeting minutes (where applicable) to ensure subject safety and compliance with 
protocol defined guidelines. 
 
12. 
USE OF INFORMATION 
 
All information regarding Cabazitaxel supplied by Sanofi to the investigator is privileged and 
confidential information.  The investigator may use this information to accomplish the study, but 
may not use it for other purposes without consent from Sanofi.  In accordance with the 
agreement between Sanofi and the investigator sponsor, complete study data must be provided to 
Sanofi.  This data and other information obtained from the clinical study may be used by Sanofi 
for the development of cabazitaxel and may be disclosed by Sanofi to regulatory authority(ies), 
other investigators, corporate partners, or consultants as deemed necessary by Sanofi. 
 
Upon completion of the clinical study and evaluation of results by Sanofi, the hospital or 
institution and/or investigator may publish or disclose the clinical trial results pursuant to the 
terms contained in the applicable Clinical Trial Agreement.

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13. 
REFERENCES 
 
1. Hussain M1, Tangen CM, Higano C, et al. Absolute prostate-specific antigen value after 
androgen deprivation is a strong independent predictor of survival in new metastatic prostate 
cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006 Aug 
20;24(24):3984-90. 
 
2.  de Bono JS, Oudard S, Ozguroglu M, et al: Prednisone plus cabazitaxel or mitoxantrone for 
metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a 
randomised open-label trial. Lancet 376:1147-54, 2010 
 
3. de Bono JS, Logothetis CJ, Molina A, et al: Abiraterone and increased survival in 
metastatic prostate cancer. N Engl J Med 364:1995-2005, 2011 
 
4. Ryan CJ, Smith MR, de Bono JS, et al: Abiraterone in metastatic prostate cancer without 
previous chemotherapy. N Engl J Med 368:138-48, 2013 
 
5. Scher HI, Fizazi K, Saad F, et al: Increased survival with enzalutamide in prostate cancer 
after chemotherapy. N Engl J Med 367:1187-97, 2012. 
 
6. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer 
before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33.  
 
7. Loriot Y, ASCO GU 2012 (abstract 213) 
 
 
 
 
 
 
 
 

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14. 
APPENDICES 
 
14.1 
Performance Status Criteria 
 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, able 
to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no evidence 
of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease. 
1 
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 
 
 
 

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14.2 
List of strong CYP3A inhibitors  
 
List of strong CYP 3A inhibitors 
 
INHIBITORS 
Maximum AUC fold 
increase 
 (AUC ratio) 
Substrate for the observed 
Maximum AUC fold increase 
Inhibitor 
Classification 
Telaprevir 
77,98 / 9,0 
tacrolimus / midazolam 
Strong 
Indinavir/RIT 
36,50 
alfentanil 
Strong 
Tipranavir/RIT 
26,91 
midazolam 
Strong 
Ritonavir 
26,41 
midazolam 
Strong 
Cobicistat (GS-9350) 19,03 
midazolam 
Strong 
Indinavir 
16,25 
vardenafil 
Strong 
Ketoconazole 
15,90 
midazolam 
Strong 
Troleandomycin 
14,80 
midazolam 
Strong 
Danoprevir/RIT 
13.42 
midazolam 
Strong 
Saquinavir/RIT 
12,48 
midazolam 
Strong 
Itraconazole 
10,80 
midazolam 
Strong 
Voriconazole 
9,40 
midazolam 
strong 
Mibefradil 
8,86 
midazolam 
strong 
Clarithromycin 
8,39 
midazolam 
Strong 
Lopinavir/RIT 
7,71 
aplaviroc 
Strong 
Elvitegravir/RIT 
6,80 
midazolam iv 
Strong 
Posaconazole 
6,23 
midazolam 
Strong 
Telithromycin 
6,0 
midazolam 
Strong 
Grapfruit Juice 
5,95 
midazolam 
Strong 
Conivaptan 
5,76 
midazolam 
Strong 
Nefazodone 
5,44 
midazolam 
Strong 
Nelfinavir 
5.29 
simvastatin 
Strong 
Saquinavir 
5.18 
midazolam 
Strong 
Boceprevir 
5.05 
midazolam 
Strong 

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14.3 
List of strong CYP 3A inducers 
 
 
Inducers 
% AUC 
decrease 
Substrate for the observed 
% AUC decrease 
Inducer 
Classification 
Rifampin 
99.7 
budesonide 
Strong 
Mitotane 
94.5 
midazolam 
Strong 
Avasimibe 
93.5 
midazolam 
Strong 
Phenytoin 
89.5 
nisoldipine 
Strong 
Carbamazepine 
86.5 
quetiapine 
Strong 
Enzalutamide 
85.9 
midazolam 
Strong 
St John’s wort* 
80 
midazolam 
Strong 
Rifabutin 
Not provided 
delavirdine 
Strong 
Phenobarbital 
76.6 
verapamil 
Strong 
*An herb (Hypericum perforatum) used for depression, anxiety and/or sleep disorders 
 
 
 
 
 
 

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14.4 
Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 
 
Response and progression will be evaluated in this study using the international criteria proposed 
by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) 
[Eur J Ca 45:228-247, 2009].  Changes in the largest diameter (unidimensional measurement) of 
the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the 
RECIST criteria. 
 
14.4.1  
Definitions 
 
Evaluable for toxicity.  All patients will be evaluable for toxicity from the time of their 
first treatment with cabazitaxel. 
 
Evaluable for objective response.  Only those patients who have measurable disease 
present at baseline, have received at least one cycle of therapy, and have had their disease 
re-evaluated will be considered evaluable for response.  These patients will have their 
response classified according to the definitions stated below.  (Note:  Patients who exhibit 
objective disease progression prior to the end of cycle 1 will also be considered 
evaluable.) 
 
Evaluable Non-Target Disease Response.  Patients who have lesions present at baseline 
that are evaluable but do not meet the definitions of measurable disease, have received at 
least one cycle of therapy, and have had their disease re-evaluated will be considered 
evaluable for non-target disease.  The response assessment is based on the presence, 
absence, or unequivocal progression of the lesions.  
 
14.4.2  
Disease Parameters 
 
Measurable disease.  Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as >20 mm by chest 
x-ray, as >10 mm with CT scan, or >10 mm with calipers by clinical exam.  All tumor 
measurements must be recorded in millimeters (or decimal fractions of centimeters). 
 
Note:  Tumor lesions that are situated in a previously irradiated area might or might not 
be considered measurable.  If the investigator thinks it appropriate to include them, the 
conditions under which such lesions should be considered must be defined in the 
protocol. 
 
Malignant lymph nodes.  To be considered pathologically enlarged and measurable, a 
lymph node must be >15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm).  At baseline and in follow-up, only 
the short axis will be measured and followed. 
 
Non-measurable disease.  All other lesions (or sites of disease), including small lesions 
(longest diameter <10 mm or pathological lymph nodes with ≥ 10 to <15 mm short axis), 
are considered non-measurable disease.  Bone lesions, leptomeningeal disease, ascites, 

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pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, 
and abdominal masses (not followed by CT or MRI), are considered as non-measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts 
should not be considered as malignant lesions (neither measurable nor non-measurable) 
since they are, by definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-
cystic lesions are present in the same patient, these are preferred for selection as target 
lesions. 
 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ and 5 
lesions in total, representative of all involved organs, should be identified as target 
lesions and recorded and measured at baseline.  Target lesions should be selected on the 
basis of their size (lesions with the longest diameter), be representative of all involved 
organs, but in addition should be those that lend themselves to reproducible repeated 
measurements.  It may be the case that, on occasion, the largest lesion does not lend itself 
to reproducible measurement in which circumstance the next largest lesion which can be 
measured reproducibly should be selected.  A sum of the diameters (longest for non-
nodal lesions, short axis for nodal lesions) for all target lesions will be calculated and 
reported as the baseline sum diameters.  If lymph nodes are to be included in the sum, 
then only the short axis is added into the sum.  The baseline sum diameters will be used 
as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
 
Non-target lesions.  All other lesions (or sites of disease) including any measurable 
lesions over and above the 5 target lesions should be identified as non-target lesions and 
should also be recorded at baseline.  Measurements of these lesions are not required, but 
the presence, absence, or in rare cases unequivocal progression of each should be noted 
throughout follow-up.  
 
14.4.3   
Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers.  All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks 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 unless the lesion(s) being 
followed cannot be imaged but are assessable by clinical exam. 
 
Clinical lesions.  Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm diameter as 

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assessed using calipers (e.g., skin nodules).  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.  This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5 mm or less.  If CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be 
twice the slice thickness.  MRI is also acceptable in certain situations (e.g. for body 
scans).   
 
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal 
resolution; however, there are many image acquisition variables involved in MRI, which 
greatly impact image quality, lesion conspicuity, and measurement.  Furthermore, the 
availability of MRI is variable globally.  As with CT, if an MRI is performed, the 
technical specifications of the scanning sequences used should be optimized for the 
evaluation of the type and site of disease.  Furthermore, as with CT, the modality used at 
follow-up should be the same as was used at baseline and the lesions should be 
measured/assessed on the same pulse sequence.  It is beyond the scope of the RECIST 
guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body 
parts, and diseases.  Ideally, the same type of scanner should be used and the image 
acquisition protocol should be followed as closely as possible to prior scans.  Body scans 
should be performed with breath-hold scanning techniques, if possible. 
 
PET-CT.  At present, the low dose or attenuation correction CT portion of a combined 
PET-CT is not always of optimal diagnostic CT quality for use with RECIST 
measurements.  However, if the site can document that the CT performed as part of a 
PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), 
then the CT portion of the PET-CT can be used for RECIST measurements and can be 
used interchangeably with conventional CT in accurately measuring cancer lesions over 
time.  Note, however, that the PET portion of the CT introduces additional data which 
may bias an investigator if it is not routinely or serially performed.   
 
Ultrasound. Ultrasound is not useful in assessment of lesion size and should not be used 
as a method of measurement.  Ultrasound examinations cannot be reproduced in their 
entirety for independent review at a later date and, because they are operator dependent, it 
cannot be guaranteed that the same technique and measurements will be taken from one 
assessment to the next.  If new lesions are identified by ultrasound in the course of the 
study, confirmation by CT or MRI is advised.  If there is concern about radiation 
exposure at CT, MRI may be used instead of CT in selected instances. 
 
Endoscopy, Laparoscopy.  The utilization of these techniques for objective tumor 
evaluation is not advised.  However, such techniques may be useful to confirm complete 
pathological response when biopsies are obtained or to determine relapse in trials where 
recurrence following complete response (CR) or surgical resection is an endpoint. 

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Tumor markers.  Tumor markers alone cannot be used to assess response.  If markers are 
initially above the upper normal limit, they must normalize for a patient to be considered 
in complete clinical response.  Specific guidelines for both CA-125 response (in recurrent 
ovarian cancer) and PSA response (in recurrent prostate cancer) have been published 
[JNCI 96:487-488, 2004; J Clin Oncol 17, 3461-3467, 1999; J Clin Oncol 26:1148-1159, 
2008].  In addition, the Gynecologic Cancer Intergroup has developed CA-125 
progression criteria which are to be integrated with objective tumor assessment for use in 
first-line trials in ovarian cancer [JNCI 92:1534-1535, 2000]. 
 
Cytology, Histology.  These techniques can be used to differentiate between partial 
responses (PR) and complete responses (CR) in rare cases (e.g., residual lesions in tumor 
types, such as germ cell tumors, where known residual benign tumors can remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment when the measurable tumor has met criteria for response or 
stable disease is mandatory to differentiate between response or stable disease (an 
effusion may be a side effect of the treatment) and progressive disease. 
 
FDG-PET  While FDG-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of FDG-PET scanning to 
complement CT scanning in assessment of progression (particularly possible 'new' 
disease).  New lesions on the basis of FDG-PET imaging can be identified 
according to the following algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a 
sign of PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the 
positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD.  If the positive FDG-PET at follow-up is not 
confirmed as a new site of disease on CT, additional follow-up CT  scans 
are needed to determine if there is truly progression occurring at that site 
(if so, the date of PD will be the date of the initial abnormal FDG-PET 
scan).  If the positive FDG-PET at follow-up corresponds to a pre-existing 
site of disease on CT that is not progressing on the basis of the anatomic 
images, this is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar 
to a biopsy in cases where a residual radiographic abnormality is thought 
to represent fibrosis or scarring.  The use of FDG-PET in this 
circumstance should be prospectively described in the protocol and 
supported by disease-specific medical literature for the indication.  
However, it must be acknowledged that both approaches may lead to false 
positive CR due to limitations of FDG-PET and biopsy 
resolution/sensitivity. 
  

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 Note:  A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an 
uptake greater than twice that of the surrounding tissue on the attenuation 
corrected image. 
14.4.4   
Response Criteria 
 
14.4.4.1 
 Evaluation of Target Lesions 
 
Complete Response (CR):  Disappearance of all target lesions.  Any 
pathological lymph nodes (whether target or non-target) must have 
reduction in short axis to <10 mm. 
 
Partial Response (PR):  At least a 30% decrease in the sum of the 
diameters of target lesions, taking as reference the baseline sum diameters 
 
Progressive Disease (PD):  At least a 20% increase in the sum of the 
diameters of target lesions, taking as reference the smallest sum on study 
(this includes the baseline sum if that is the smallest on study).  In addition 
to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm.  (Note:  the appearance of one or more new 
lesions is also considered progressions). 
 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD, taking as reference the smallest sum 
diameters while on study 
 
14.4.4.2 
Evaluation of Non-Target Lesions 
 
Complete Response (CR):  Disappearance of all non-target lesions and 
normalization of tumor marker level.  All lymph nodes must be non-
pathological in size (<10 mm short axis) 
 
Note:  If tumor markers are initially above the upper normal limit, they 
must normalize for a patient to be considered in complete clinical 
response. 
 
Non-CR/Non-PD:  Persistence of one or more non-targetlesion(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.  Unequivocal 
progression should not normally trump target lesion status.  It must be 
representative of overall disease status change, not a single lesion increase.     
 
Although a clear progression of “non-target” lesions only is exceptional, 
the opinion of the treating physician should prevail in such circumstances, 

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and the progression status should be confirmed at a later time by the 
review panel (or Principal Investigator). 
 
14.4.4.3 
 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).  The patient's best response assignment will depend on 
the achievement of both measurement and confirmation criteria. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
 
 
 
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is 
increasingly used as an endpoint for assessment of efficacy in some trials so to assign this 
category when no lesions can be measured is not advised 
 
 
Target 
Lesions 
Non-Target Lesions 
New 
Lesions 
Overall Response 
Best Overall Response when  
Confirmation is Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-PD/not 
evaluated 
No 
PR 
SD 
Non-CR/Non-PD/not 
evaluated 
No 
SD 
documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
*      See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
**    Only for non-randomized trials with response as primary endpoint. 
***  In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease progression. 
 
Note: 
Patients with a global deterioration of health status requiring discontinuation of treatment without objective 
evidence of disease progression at that time should be reported as “symptomatic deterioration.”  Every effort 
should be made to document the objective progression even after discontinuation of treatment. 

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14.4.5   
Duration of Response 
 
Duration of overall response:  The duration of overall response is measured from 
the time measurement criteria are met for CR or 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 CR is measured from the time measurement criteria are 
first met for CR until the first date that progressive disease is objectively 
documented.  
 
Duration of stable disease:  Stable disease is measured from the start of the 
treatment until the criteria for progression are met, taking as reference the 
smallest measurements recorded since the treatment started, including the baseline 
measurements.  
 
 
 
 

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14.5 Correlate Sample Submission Form 
 
UC Davis Sample Submission Form: UCDCC#261 – Cabazitaxel in CRPC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Information: 
Patient Study ID# 
 
 
Pt Initials (FML):  
 
 
 
 
 
 
Research Blood 
Timepoint: 
□ 
Screening 
□ End of Cycle 4 
□ Off Treatment 
 
 
(leave blank if shipping tumor submission only) 
Collection Date: 
 
 
Time of 
Collection: 
 
 
 
 
 
 
 
 
  
Shipper Contact Information: 
Packaged by: 
 
Phone 
#: 
 
Email 
Address: 
 
Specimen Shipping Instructions: 
Draw: 
1 x 10 ml Purple EDTA Tube (BD# 366643)  
 
 
 
1 x 10 mL Red top Serum Tube (BD# 367820) 
EDTA and Serum tubes: Process blood according to instructions in protocol Section 8.0.  Ship frozen aliquots on dry ice.   
Packaging shipment:   Frozen samples should be shipped on sufficient dry ice and in accordance with all applicable state and 
federal laws. Please include completed requisition forms for all samples submitted and contact the lab manager when 
shipping.  Packages can be shipped Monday-Wednesday ONLY.   
 
Slide Submission:  Prepare slides as described in Section 8.0 
Packaging shipment:  Archival tissue slides may be sent at ambient temperatures with a room-temperature gel pack to 
protect specimen from temperature fluctuations. In summer months when outdoor temperatures can exceed 90°F, please 
pack specimens with a refrigerated gel pack.  Please include a completed requisition form and a copy of the path report for 
each sample submitted and contact the lab manager when shipping. Packages can be shipped Monday-Wednesday ONLY.   
 
Packaged Specimens should be shipped using 
FedEx Priority Overnight to: 
 
When shipping, please send email notification 
including FedEx tracking number to: 
         
 
 
 
 
Molecular Pharmacology Shared Resource Use Only 
Lab Specimen #______________________  
 
Date Received: 
/
/
 
Condition of Specimen: 
 
 
 
 
□ 
Usable as received 
 
 
 
 
Received/Logged By:  ________________ 
□ 
Usable, not optimal: _____________  
 
□ 
Not usable, insufficient or incorrect 
 
 
 
□ 
Not usable, other:________________  
 
FedEx Tracking #:   ______________________ 
 
 
 
 
 
 
 
 
 
 

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14.6    Multicenter Guidelines 
 
A. Before registration, the site study coordinator should check to make sure that the 
corresponding Investigational Drug Service or equivalent has study drug in stock. 
 
B. Registrations for this Phase II protocol must be made through the OCR of the University 
of California, Davis Comprehensive Cancer Center between the hours of 9am and 3pm 
(Pacific Time), Monday through Friday (except holidays).  Documentation of current 
IRB approval of this protocol by non-UC Davis institutions must be on file prior to 
registration of patients at these institutions. 
 
C. Pre-study laboratory tests, scans, and x-rays (where applicable), must be completed prior 
to registration, within the time frame specified in the protocol.  The eligibility checklist 
must be completed.  Patients must sign an informed consent prior to registration.  
 
D. Patients may be registered up to 72 hours prior to treatment initiation. All pages of the 
signed consent, completed checklist and reports from all pre-study laboratory tests, scans 
and x-rays (where applicable) must be faxed and/or emailed to UC Davis OCR 
 in order to register the patient. The UC Davis Protocol Coordinator will review 
these documents and fax and/or email a registration confirmation (which includes a 
subject ID number). 
 
Reminder: Confirm eligibility for ancillary studies and willingness to participate at the 
same time as eligibility for the treatment study. 
 
E. If the patient is to be registered the same day as the proposed treatment start date, the UC 
Davis Study Coordinator must be notified by fax and/or 24 hour prior to proposed 
treatment start date that the site has a patient to register.   
 
F. A patient failing to meet all protocol requirements may not be registered.  If you have any 
questions regarding eligibility, contact the coordinating site PI or Study Coordinator.   
 
NOTE: Administration of study medication may not be initiated until the registration 
confirmation has been received. 
 
 
 
 
 

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14.7 
    Data Submission Schedule 
All data will be collected using UC Davis data collection forms. Any and all source 
documentation should be maintained. 
 
 
 SUBMIT WITHIN 24 HOURS OF REGISTRATION:  
Patient Registration Form  
 
 SUBMIT WITHIN 14 DAYS OF REGISTRATION:  
In‐House Pre‐Study Evaluation Form (IH‐102)  
 
 SUBMIT WITHIN 7 DAYS OF SCREENING FAILURE:  
Patient Screen Failure Form  
 
 SUBMIT WITH 14 DAYS OF CYCLE COMPLETION:  
Adverse Event/Drug Relationship Form  
 
 
 SUBMIT WITHIN 14 DAYS OF END OF EACH TREATMENT CYCLE:  
In‐House Treatment Cycle Form - Oral  
 
 SUBMIT WITHIN 14 DAYS OF EACH RESPONSE ASSESSMENT:  
Tumor Measurement Log  
 
 SUBMIT WITHIN 14 DAYS OF OFF TREATMENT:  
Off Treatment/In Follow-up/Off Study/Expiration Form (IH‐301)  
 
 SUBMIT WITHIN 14 DAYS OF KNOWLEDGE OF DEATH IF PATIENT IS STILL ON 
STUDY OR 30–DAYS IF OFF STUDY:  
Off Treatment/In Follow-up/Off Study/Expiration Form (IH‐301)  
 
 SUBMIT WITHIN 2 DAYS OF KNOWLEDGE OF PROTOCOL DEVIATION:  
Notice of Protocol Deviation  
 
 ALL SERIOUS ADVERSE EVENTS MUST BE REPORTED AS OUTLINED IN THE 
PROTOCOL.