Clinical trial NCT04598321
Conditions: BRCA1 Mutation BRCA2 Mutation Ovarian Cancer Fallopian Tube Cancer High Grade Serous Carcinoma
Sponsor: Brown University
Start date: 2021-03-29; Completion date: 2022-12-06
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Ovarian cancer is the most fatal gynecologic cancer; in the US alone an estimated 22,000 women will be diagnosed in 2019, with over 13,000 dying of the disease. Approximately half of epithelial ovarian cancers (EOC) exhibit defective DNA repair through alterations in the homologous recombination (HR) pathway, with 14% accounted for by germline mutations in BRCA genes (mBRCA); this goes up to about one in five (20%) women when one includes tumor-associated (somatic) mBRCA.The approach to women with mBRCA-associated ovarian cancer has heralded precision treatment in our field with the availability of PARP inhibitors. Now indicated as treatment for women with documented mBRCA (genomic or somatic), it also has shown significant benefits for women with recurrent EOC who respond to platinum-based therapy when administered as maintenance treatment.

Detailed description:

Arms: arm 1: Talazoparib monotherapy as 1 mg capsule orally on a daily basis for three cycles, defined as a 21-day period, prior to surgery. Volunteers will continue treatment to complete three cycles, unless disease progression or unacceptable toxicity occurs.Volunteers who complete neoadjuvant treatment with talazoparib should undergo surgical cytoreduction within three weeks of their last dose of talazoparib. All volunteers should then undergo standard of care adjuvant therapy using carboplatin and paclitaxel. For volunteers, who agree to continue talazoparib as maintenance therapy, treatment should begin three weeks (+/- 2 weeks) from the end of adjuvant chemotherapy or after cytoreductive surgery alone.
Interventions: intervention 1: Talazoparib Oral Capsule
Intervention descriptions: intervention 1: An orally available PARP inhibitor for the treatment of advanced breast cancer with germline BRCA mutations.

Protocol documents:
Prot_SAP_ICF_000.pdf: 
 BrUOG 390: Version Date: 3/22/2020, 4/6/2020, 7/22/2020, 8/11/2020, 10/30/20, post FDA: 11/13/20, 
11/23/20; 1/7/21, A#1 6/9/21 
1 
 
 
 
 
 
 
TITLE: BrUOG 390: Neoadjuvant treatment with Talazoparib for women with 
newly diagnosed, advanced ovarian cancer associated with a mutation in BRCA1 or 
BRCA2 (mBRCA): A Phase 2 Feasibility Trial 
 
 
Principal Investigator: Don S. Dizon, MD, Lifespan Cancer Institute, Rhode Island 
Hospital 
 
Co-Principal Investigator: Cara Mathews, MD, Program in Women’s’ Oncology, 
Women & Infants Hospital of Rhode Island 
 
Study Monitor & Central Coordinating Group: Brown University Oncology 
Research Group 
 
 
 
 
 
Original Version and Date: 3/22/2020   
  
 
IND Exempt: 153723 
 
 
 
 
 
Amendment #1: 6/9/21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
SCHEMA. .............................................................................................................................. 4 


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2 
OBJECTIVES ....................................................................................................................... 5 
2.1 
Primary Objective ............................................................................................................ 5 
2.2 
Secondary Objectives ...................................................................................................... 5 
2.3 
Exploratory objective ...................................................................................................... 5 
3 
BACKGROUND AND RATIONALE ................................................................................ 6 
3.1 
Ovarian cancer ................................................................................................................. 6 
3.2 
Ovarian cancer associated with mutations in BRCA1 or BRCA2 (mBRCA) ................. 6 
3.3 
Talazoparib ...................................................................................................................... 7 
3.3.3. 
Summary of studies in human volunteers .............................................................. 11 
3.3.4. 
Absorption, Distribution, Metabolism, and Excretion ........................................... 12 
3.3.5. 
Drug-drug interactions ........................................................................................... 13 
3.3.6. 
Population pharmacokinetics ................................................................................. 13 
3.3.7. 
Safety profile ......................................................................................................... 14 
3.4 
Rationale ........................................................................................................................ 14 
4 
VOLUNTEER SELECTION, ELIGIBILITY, AND INELIGIBILTY CRITERIA .... 15 
4.1 
Eligibility Criteria .......................................................................................................... 15 
4.2 
Ineligibility Criteria ....................................................................................................... 16 
4.3 
Inclusion of Gender, Racial, and Sexual Minorities ...................................................... 18 
5 
REGISTRATION PROCEDURES ................................................................................... 18 
6 
TREATMENT PLAN ......................................................................................................... 19 
6.1 
Summary of the treatment plan ..................................................................................... 19 
6.2 
Talazoparib .................................................................................................................... 19 
6.3 
Pre-treatment criteria for Talazoparib ........................................................................... 24 
6.4 
Criteria for discontinuation of protocol treatment ......................................................... 24 
6.5 
General concomitant medication and supportive care guidelines ................................. 25 
7 
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS .......................... 25 
7.1 
Serious Adverse Events Reported from Clinical Trials ................................................. 25 
7.2 
Monitoring of Adverse Events and Period of Observation ........................................... 28 
7.3 
BrUOG Adverse Event Reporting Requirements .......................................................... 28 
7.4 
Serious Adverse Event Reporting Procedures ............................................................... 29 
7.5 
BrUOG Responsibility regarding reporting .................................................................. 31 
7.6 
IND Annual Reports (if IND study only) ...................................................................... 32 
7.7 
Adverse event updates/IND safety reports .................................................................... 32 
8 
ORDERING TALAZOPARIB .......................................................................................... 33 
8.1 
Initial orders .................................................................................................................. 33 
8.2 
Resupply ........................................................................................................................ 33 


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8.3 
Drug excursions ............................................................................................................. 33 
8.4 
Questions on drug expiration, delayed shipment, etc. ................................................... 33 
8.5 
Accountability ............................................................................................................... 33 
8.6 
Destruction and return ................................................................................................... 34 
9 
STUDY CALENDAR ......................................................................................................... 34 
9.1 
Pre-Treatment assessments ............................................................................................ 34 
9.2 
On-treatment assessments ............................................................................................. 35 
10 
ASSESSMENTS IN FOLLOW-UP ................................................................................... 36 
11 
Measurement of EFFECT .................................................................................................. 37 
11.1 
Antitumor Effect – Solid Tumors .............................................................................. 37 
12 
STATISTICAL CONSIDERATIONS .............................................................................. 42 
12.1 
Primary objectives ..................................................................................................... 42 
12.2 
Secondary objectives ................................................................................................. 43 
12.3 
Exploratory objectives ............................................................................................... 43 
13 
REGULATORY CONSIDERATIONS ............................................................................ 43 
13.1 
Good Clinical Practice ............................................................................................... 44 
13.2 
Patient Confidentiality ............................................................................................... 44 
13.3 
Protocol Compliance ................................................................................................. 44 
13.4 
On-site Audits ............................................................................................................ 44 
13.5 
Drug Accountability .................................................................................................. 44 
13.6 
Premature Closure of the Study ................................................................................. 45 
13.7 
Record Retention ....................................................................................................... 45 
14 
DATA SAFETY AND MONITORING BOARDS........................................................... 45 
15 
PUBLICATION PLAN ...................................................................................................... 46 
16 
REFERENCES ................................................................................................................... 46 
Appendix A. Pill Calendar ..................................................................................................... 50 
Appendix B. Informed Consent ............................................................................................. 51 
Appendix C BrUOG checklist for patient registration ........................................................ 62 
Appendix D. FDA MedWatch Reporting Checklist for site to submit with report .......... 68 
  
 
 
 
 
 
 
 
 


 BrUOG 390: Version Date: 3/22/2020, 4/6/2020, 7/22/2020, 8/11/2020, 10/30/20, post FDA: 11/13/20, 
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1 
SCHEMA.  
 
 


 BrUOG 390: Version Date: 3/22/2020, 4/6/2020, 7/22/2020, 8/11/2020, 10/30/20, post FDA: 11/13/20, 
11/23/20; 1/7/21, A#1 6/9/21 
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2 
OBJECTIVES 
 
2.1 
Primary Objective 
 
To determine feasibility as defined by:  
 
• Enrollment of 30 volunteers within two years of trial activation 
• No more than three volunteers experiencing disease progression on 
talazoparib 
• No more than two volunteers experiencing >grade 3 toxicity 
 
2.2 
Secondary Objectives 
 
To determine preliminary effectiveness of talazoparib in this population by: 
 
• Assessing the clinical objective response rate after nine weeks of 
talazoparib  
• Define the rate of optimal cytoreduction and resection to no residual 
disease (R0) following talazoparib treatment. 
 
 
2.3 
Exploratory objective   
 
The Chemotherapy Response Score (CRS) has been proposed as a reproducible 
measure of neoadjuvant carboplatin and paclitaxel, specifically in high grade 
serous carcinoma. We will collect the CRS scores in this trial to determine if it is 
useful in this setting.  
 
All volunteers will be expected to undergo adjuvant chemotherapy using 
carboplatin and paclitaxel; however, for patients who have no evidence of disease 
at the time of interval cytoreduction (CRS3) the options to forego chemotherapy 
and continue on talazoparib can be considered following discussion with the Co-
Principal Investigators. Following this, all volunteers who did not progress during 
talazoparib during the neoadjuvant period will be offered the option to reinitiate 
talazoparib to complete a two-year adjuvant course. For those who opt for 
talazoparib following adjuvant chemotherapy, we will measure the proportion 
who are progression-free at 3 years (3y PFS), measured from day 1 of 
maintenance treatment.  
 
 


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3 
BACKGROUND AND RATIONALE 
 
3.1 
Ovarian cancer 
 
Ovarian cancer is the most fatal gynecologic cancer; in the US alone an estimated 22,000 
women will be diagnosed in 2019, with over 13,000 dying of the disease.2 Approximately 
half of epithelial ovarian cancers (EOC) exhibit defective DNA repair through alterations 
in the homologous recombination (HR) pathway, with 14% accounted for by germline 
mutations in BRCA genes (mBRCA); this goes up to about one in five (20%) women 
when one includes tumor-associated (somatic) mBRCA.3  
 
For women presenting with advanced ovarian cancer (Stage II to IV disease), 
neoadjuvant chemotherapy (NACT) has become a more widely accepted approach in 
treating advanced disease (stage III and IV). The adoption of NACT is based on multiple 
phase III trials showing similar benefits in terms of OS when NACT is compared with the 
usual standard of primary surgery followed by adjuvant chemotherapy.   
 
Despite this more routine acceptance of NACT for the patient presenting with advanced 
ovarian cancer, the optimal treatment of these patients after planned interval 
cytoreduction remains unresolved. In other words, it may be that the lack of any survival 
advantage with NACT is related to the administration of the same chemotherapy 
prescription after the interval cytoreduction (i.e., in the adjuvant setting); the results of 
two randomized trials support the idea that the administration of a similar regimen in the 
neoadjuvant and adjuvant settings may result in a lack of survival advantage.4,5 
 
Current pathology practice includes reporting pathologic assessment of disease response 
on surgical cancer specimens after NACT, called the Chemotherapy Response Score 
(CRS). This is a reproducible three-tier score, and demonstrates prognostic significance 
for progression-free survival (CRS 1 and 2 v 3: median, 15 v 19 months; p=0.016).1  
 
3.2 
Ovarian cancer associated with mutations in BRCA1 or BRCA2 (mBRCA) 
 
The approach to women with mBRCA-associated ovarian cancer has heralded precision 
treatment in our field with the availability of PARP inhibitors. Now indicated as 
treatment for women with documented mBRCA (genomic or somatic), it also has shown 
significant benefits for women with recurrent EOC who respond to platinum-based 
therapy when administered as maintenance treatment. These data have led to the FDA 
approval of three PARP inhibitors for use in EOC, though indications slightly differ 
(Table 1). The results of the SOLO-1 trial led to the FDA approval of olaparib as a 
maintenance therapy after upfront chemotherapy for women with mBRCA-associated 
ovarian cancer.6 In that trial, almost 400 women with newly diagnosed stage III-IV high 
grade serous or endometrioid cancers who had a clinical complete or partial response to 
platinum-based therapy were randomly assigned in 2:1 fashion to olaparib (300mg BID) 
or placebo. Compared to placebo, maintenance olaparib significantly prolonged 3-year 
progression-free survival (60 vs 27%, respectively, HR 0.30, p<.001).  


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Continued efforts aim to maximize the impact of PARP inhibitors for women with 
ovarian cancer, with or without an mBRCA, and multiple trials are ongoing in the upfront 
and recurrent disease setting.  
 
Recently, Litton, et al. reported the results of a feasibility trial in which she aimed to 
enroll volunteers with a known mBRCA and operable breast cancer (clinical stage I to 
III, tumor size ≥1 cm) to neoadjuvant talazoparib.7 The treatment course was to be for 8 
weeks after which standard neoadjuvant anthracycline/taxane chemotherapy was to be 
administered. Her aim was to prove she could enroll 20 volunteers in 2 years. She was 
able to enroll 13 volunteers in 8 months, and impressively, all volunteers experienced a 
response with a mean tumor volume reduction of 88% (range, 30 to 98%). For women 
with triple-negative breast cancer, residual cancer burden was recorded as 0 or 1 at 
surgery. The study continues with an aim to enroll a cohort of 20 women with treatment 
using talazoparib for up to 6 months before definitive surgery. This study marks the first 
trial of true precision therapy in women with mBRCA-associated breast cancer.  
 
Agent 
Trial 
Volunteer and Study criteria 
Efficacy 
Toxicity 
ROC 
HGS 
gBRCA 
Maint 
Niraparib 
NOVA8 
(n=546) 
√ 
√ 
√ 
+++PFS in gBRCA+ 
and gBRCA- 
Nausea, 
Thrombocytopenia, 
Fatigue, Anemia 
Olaparib 
SOLO-
29  
(n=295) 
√ 
√ 
√ 
√ 
+++PFS 
Nausea, Fatigue, 
Anemia, Emesis 
Phase 
210 
(n=193) 
√ 
√ 
√ 
 
30%ORR 
40%SD8w 
Fatigue, Nausea, 
Anemia, Abdominal 
pain 
Rucaparib 
ARIEL-
311  
√ 
≥3 
lines 
√ 
√ 
+++PFS in gBRCA+, 
LOH+, ITT 
Nausea, Fatigue, 
Anemia, Constipation  
Phase 
212  
(n=106) 
√  
≥2 
lines 
√ 
√  
Somatic 
allowed 
54% ORR 
9m mDOR 
Nausea, Fatigue, 
Anemia, Abdominal 
pain  
Table 1. FDA Indications of 3 available PARP Inhibitors for ovarian cancer 
 
3.3 
Talazoparib 
 
Talazoparib (PF-06944076, formerly BMN 673, MDV3800) is a potent, orally 
bioavailable, small molecule poly(adenosine diphosphate [ADP]-ribose) polymerase 
(PARP) inhibitor (PARPi) that is in development for the treatment of a variety of human 
cancers. PARPis exert antitumor activity via both inhibition of PARP catalytic activity 
(including inhibition of poly-ADP-ribosylation [PARylation]) and PARP trapping. 
 
In vitro pharmacology studies with talazoparib demonstrated potent and selective 
inhibition of PARP1 (50% inhibitive concentration [IC50] = 0.7 nM) and PARP2 (IC50 = 
0.3 nM) catalytic activity in a biochemical assay. Robust cytotoxicity following 
talazoparib treatment was observed in a panel of breast, prostate, pancreatic, and 
colorectal cancer cell lines with defects in DNA damage repair pathways. Evaluation of 


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PARP trapping in breast and prostate cancer cell lines treated with talazoparib resulted in 
increased trapping in the presence of single-strand break inducing agent methyl methane 
sulfonate (MMS). The effects were clearly evident in the BRCA1-mutant MDA-MB-436 
breast cancer, which is sensitive to talazoparib-induced cytotoxicity, compared to the less 
sensitive BRCA1-mutant breast cancer HCC1954 line. PARP trapping has also been 
shown for the BRCA2-mutant DU145 prostate cancer cell line. Additionally, a 
multiparametric DDR assay in the DU145 cell line also showed that talazoparib treatment 
induced S-phase cell-cycle arrest, increased S-phase specific and total dsDNA breaks 
(measured by H2AX), increased early apoptosis (measured by cleaved caspase 3 [CC3]), 
and decreased cell population growth, compared to vehicle treated cells. The reduced 
population growth and cytotoxicity observed in the DDR assays are consistent with the 
proposed mechanisms of action for talazoparib: catalytic activity inhibition and PARP 
trapping. 
 
In vivo, antitumor efficacy of single agent talazoparib was better than carboplatin in a 
breast cancer PDX model when dosed orally QD at 0.3 mg/kg. Breast cancer PDX 
models (one each with mutated BRCA1 and mutated BRCA2, and 3 models with wild 
type BRCA1/2) evaluated with talazoparib dosed BID at 0.07 mg/kg or 0.15 mg/kg 
showed that talazoparib elicited the strongest, statistically significant (compared to 
vehicle), dose dependent TGI response (100% TFS) in the BRCA1-mutated PDX model, 
but also elicited statistically significant TGI responses in the BRCA2-mutated model and 
BRCA1/2 wild type models. While activity was most robust in the BRCA1 mutated 
model, talazoparib was also active in the BRCA2 mutant and in the presence of wild type 
BRCA1/2, possibly due to other unknown DDR-related mutations.13 
 
3.3.1. Summary of nonclinical studies 
 
Talazoparib is a potent inhibitor of PARP1 and PARP2 catalytic activities and has 
demonstrated potency and selectivity toward PARP1 and PARP2 in vitro, as well as 
robust cytotoxicity in a panel of cell lines with defects in the DDR pathways. Evaluation 
of the potency and selectivity of talazoparib in a PARP inhibition enzyme assay was 
conducted with a panel of 13 PARP enzymes and demonstrated IC50 values for PARP1 
and PARP2 of 0.7 nM and 0.3 nM, respectively.  
 
Talazoparib also had activity toward PARP3 (IC50, 22 nM), TNKS1 (PARP5a; IC50, 
13.5 nM), and TNKS2 (PARP5b; IC50, 4.7 nM). Assessment of talazoparib for cytotoxic 
activity in a panel of breast, prostate, and pancreatic cancer cell lines harboring defects in 
DDR pathways, demonstrated mean IC50 values of ≤5 nM. 
 
PARP trapping was measured in breast cancer cell lines treated with talazoparib over a 
concentration range that approximately covered an order of magnitude difference from  
the free Cav exposure achieved in volunteers and the IC90 for PARylation inhibition.  
Results showed increased trapping in the presence of MMS, an alkylating agent that 
induces ssDNA break, in the BRCA1-mutant MDA-MB-436 cell line, which was highly 
sensitive to talazoparib cytotoxicity and reduced trapping in the less sensitive BRCA1-
mutant HCC1954 cell line. Multiparametric DDR assays in the BRCA2 mutated DU145 


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prostate cancer cell line were conducted using a range of clinically relevant talazoparib 
concentrations in the presence and absence of the DNA alkylating agent TMZ, which is 
used as a tool to further evaluate the functional effects of talazoparib. Talazoparib 
induced S phase cell cycle arrest, increased in S-phase specific dsDNA breaks (measured 
by H2A histone family, member X, gamma subunit, γH2AX), increased early apoptosis 
(measured by CC3), and resulted in decrease in cell proliferation compared to vehicle 
treated cells. 
 
In vivo, antitumor efficacy of single agent talazoparib administered at 0.3 mg/kg QD was 
higher than carboplatin treatment in a breast cancer PDX model. Additional breast cancer 
PDX models (one with a BRCA1 mutation, one with a BRCA2 mutation, and 3 models 
with wild type BRCA1/2) were evaluated with talazoparib dosed at 0.07 mg/kg or 0.15 
mg/kg BID for 34 or 35 days. Talazoparib treatment was most effective in the BRCA1 
mutant model, resulting in percent ratio between the mean tumor volume of the treated 
group and the mean tumor volume of the control group (T/C%) of 0.39% for the 0.15 
mg/kg dose level where 100% of the mice had complete tumor regressions at study 
termination (TFS). The BRCA2 mutant model showed statistically significant T/C% of 
3.48% and 60% TFS, as did one of the 3 wild type BRCA1/2 models (T/C% = 0.32%, 
TFS = 80%) at 0.15 mg/kg, while the other 2 models exhibited modest effects. For the 
PDX models, the mean unbound Cav values at 0.07 and 0.15 mg/kg were approximately 
dose proportional and were 0.852 nM and 1.86 nM, respectively. 
 
In secondary pharmacology assessments, no activity greater than 50% of a maximal 
response was observed for talazoparib indicating there is minimal potential for secondary 
(off-target) pharmacology at clinically relevant exposures. In addition, there were no 
talazoparib-related effects on respiratory or CNS parameters following a single oral 
administration to rat in safety pharmacology studies, and there were no effects in a hERG 
assay at concentrations up to 100 μM (38035 ng/mL) or 6966-fold above the observed 
unbound human clinical exposure at 1 mg QD human dose based on mean unbound 
steady state Cmax of 5.46 ng/mL.  
 
Further details of the nonclinical evaluation of talazoparib are available in the IB. 13 
 
3.3.2. Pharmacology of Talazoparib 
 
Talazoparib activity was assessed with a panel of 13 PARP enzymes using a biochemical 
assay that measures incorporation of biotin-NAD+ in ADP-ribose polymers onto histone 
proteins (Study PF-06944076_02Nov17_092045). Talazoparib shows activity below 10 
nM for PARP1 (0.7 nM), PARP2 (0.3 nM) and Tankyrase-2 (TNKS2, 4.7 nM), inhibition 
below 25 nM for PARP3 and TNKS1 and weak to no inhibition for the remainder of the 
enzymes tested. 
 
Talazoparib was assessed for cytotoxic activity in cancer cell lines harboring defects in 
DNA repair pathways (Study BMN673-10-093). Talazoparib was cytotoxic to BRCA-
deficient Capan-1 and MX-1 cells in culture, with IC50 values of 5.0 nM and 0.3 nM, 
respectively. Talazoparib was also highly cytotoxic to PTEN-deficient MDA-MB-468, 


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LNCaP, and PC-3 cells with IC50 values of 3.7 nM, 4.3 nM, and 4.4 nM, respectively, 
and MLH1 mutated hematocrit (HCT)-116 (IC50 = 10.6 nM). In contrast, the IC50 values 
of talazoparib in normal human primary cell line MRC-5 and other tumor cell lines 
(LoVo, MDA-MB-231, and A549) without reported DNA repair-related mutations were 
much higher (>250 nM to >1000 nM).  
 
Talazoparib antitumor activity was benchmarked against carboplatin (Study MDVT-
20160830B [MDV3800P058]) in a breast cancer PDX model. The 3 test groups (n = 
7/group) received vehicle, talazoparib administered orally QD at 0.3 mg/kg, or 
carboplatin administered IP at 30 mg/kg once weekly. Talazoparib treatment resulted in 
statistically significant TGI (108%; p = 0.031) versus carboplatin treatment (TGI 67%; p 
= 0.178). 
 
For in vivo studies, the oral route of exposure was selected for these studies since it is the 
intended route of clinical administration. To evaluate potential effects on the CNS, 
talazoparib was administered as a single oral dose to male rats at 0, 0.3, 1, and 3 mg/kg. 
The rats were volunteered to a modified Irwin battery to detect potential effects on central 
and peripheral nervous systems at baseline and up to 24 hours post-dose. There were no 
talazoparib-related effects on the parameters evaluated in modified Irwin battery of 
neurological assessments including home cage, hand-held, open-field or elicited response 
observations at doses up to 3 mg/kg. In addition, no microscopic pathology changes were 
seen in the brain in any of the repeat-dose toxicity studies. Toxicokinetic parameters were 
not measured in this study, but based on the 5-day rat study, maximum mean unbound 
plasma concentration at 3 mg/kg/day was 62.6 ng/kg, which is 11.4x the observed 
unbound human Cmax concentration at the 1 mg QD clinical dose (5.46 ng/mL). 
 
Talazoparib was administered as a single oral dose to male rats at 0, 0.3, 1 or 3 mg/kg to 
assess potential effects on the respiratory system over a 5.5-hour period using whole body 
plethysmography at baseline and then starting at 0.5 and 24 hours postdose. Tidal volume 
was decreased as much as 12% (relative to control) in all dose groups administered 
talazoparib. These generally nondose dependent decreases in tidal volume were offset by 
the non-statistically significant increases in respiration rate so that there was no overall 
change in minute volume. Toxicokinetic parameters were not measured in this study, but 
based on the 5-day rat study, maximum mean unbound plasma concentration at 3 mg/kg 
(the highest dose tested) was 62.6 ng/mL and is 11.4x the observed unbound human Cmax 
concentration at the 1 mg QD clinical dose (5.46 ng/mL). Furthermore, there were no 
talazoparib-mediated adverse clinical signs associated with the respiratory system in the 
repeat-dose toxicity studies of up to 13-weeks duration in rats and dogs. 
 
To evaluate the potential effect on the cardiovascular system, talazoparib was evaluated 
for its effect on binding to the hERG potassium channel stably expressed in human 
embryonic kidney (HEK-293) cells. Talazoparib inhibited the hERG current 6.7%, 14.2% 
and 33.4% at concentrations of 10, 30, and 100 μM. Due to solubility limitations the 
highest dose that could be tested was 100 μM and an IC50 could not be calculated since 
50% inhibition was not achieved at the concentrations tested. Thus, the IC50 for hERG 
inhibition is considered >100 μM (38000 ng/mL) and is approximately >6996x the 


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observed unbound human clinical exposure at 1 mg QD human dose based on mean 
unbound steady state Cmax of 5.46 ng/mL.  
 
To further evaluate the potential for talazoparib to affect the cardiovascular system in 
vivo, ECG assessments were added on to the repeat GLP dog studies. No effects on 
ECGs were noted at doses of up to the highest dose tested (0.1 mg/kg) with mean 
unbound plasma exposures corresponding to 3.5x above human clinical exposure at 1 mg 
QD dose based on mean unbound steady state Cmax of 5.46 ng/mL. 
 
Further details of the pharmacology of talazoparib are available in the Investigator’s 
Brochure. 13  
 
3.3.3. Summary of studies in human volunteers 
 
The single dose PK of talazoparib have been evaluated in a total of 7 clinical studies, of 
which 6 were conducted in volunteers with cancer (Studies PRP-001, PRP-002, 
MDV3800-01, MDV3800-03, MDV3800-04, and MDV3800-14) and 1 in healthy 
volunteers (Study 673-103). 
 
After administration of a single 1 mg dose of talazoparib capsules to volunteers with 
cancer, the median time to reach maximum plasma concentration (Tmax) was ranging 
from 1.0 to 2.0 hours across studies. The median Tmax was 0.5 hour following 
administration of talazoparib solution in Study MDV3800-03. The geometric mean 
Cmax ranged from 4.35 to 8.79 ng/mL and the geometric mean area under concentration-
time curve from time 0 to infinity (AUCinf) ranged from 116 to 220 ng•h/mL. Talazoparib 
was eliminated slowly with a mean t½ ranging from 62.4 to 98.1 hours. It should be 
noted that the t½ value obtained from Study PRP-001 might be an underestimate as the 
PK sampling time was only up to 168 hours versus 504 hours in Study MDV3800-03.  
 
The talazoparib geometric mean apparent volume of distribution (Vz/F) values estimated 
ranged from 447 to 847 L, which is significantly greater than total body water (42 L), 
indicating that talazoparib extensively distributes to peripheral tissues. The geometric 
mean apparent oral clearance (CL/F) values estimated for talazoparib ranged from 4.55 to 
7.71 L/hour. The geometric mean renal clearance (CLr) ranged from 2.76 to 3.44 L/hour, 
indicating that urinary excretion was a major route of elimination for talazoparib. 
The talazoparib geometric mean CL/F value after administration of a single 0.5 mg 
talazoparib dose to healthy volunteers in Study 673-103 was 7.99 L/hour and 8.19 L/hour 
in the fasted and fed conditions, respectively. This value was generally in a comparable 
range with that observed in volunteers following a single dose of talazoparib at various 
dose levels (4.55 to 7.71 L/hour). In addition, the t½ of talazoparib in healthy volunteers 
ranged from 81.3 to 208 hours (Study 673-103), which is within the mean range observed 
across studies conducted in volunteers receiving a single dose of talazoparib at various 
dose levels (52.9 to 229 hours, Study PRP-001). These results collectively indicate that 
the PK of talazoparib was comparable between volunteers with cancer and healthy 
volunteers. 
 


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The PK of talazoparib following multiple oral daily doses was evaluated in a total of 
6 studies in volunteers with cancer (Studies PRP-001, PRP-002, 673-201, 673-301, 
MDV3800-01, and MDV3800-14). Following repeated 1 mg QD dosing to steady state, 
talazoparib was rapidly absorbed with a median Tmax ranging from approximately 1.0 to 
2.0 hours across studies. Talazoparib was eliminated slowly, with a geometric mean CL/F 
ranging from 4.80 to 5.53 L/hour. The mean plasma t½ was 57.8 hours (Study PRP-001), 
which may be an underestimate as the last PK sampling time was at 168 hours postdose. 
The geometric mean CLr was 3.34 L/hour, 3.32 L/hour and 2.74 L/hour in Studies PRP-
001, PRP-002, and MDV3800-01 (Group A), respectively. 
 
The talazoparib geometric mean Cmax values ranged from 11.4 to 19.1 ng/mL and the 
geometric mean area under the concentration-time curve for a dosing interval (AUCγ) 
values ranged from 126 to 208 ng•h/mL. The talazoparib geometric mean 
steady-state pre-dose plasma concentration (Ctrough) values ranged from 2.99 to 4.95 
ng/mL. 13 
 
3.3.4. Absorption, Distribution, Metabolism, and Excretion 
 
Based on the urinary excretion data from a Phase 1 mass-balance and metabolism study 
of talazoparib (MDV3800-03 [C3441003]), the absolute bioavailability is at least 54.6% 
with fraction absorbed of at least 68.7%. The talazoparib median Tmax values ranged from 
1.0 to 2.0 hours after single and multiple 1 mg oral dosing of talazoparib capsules in 
volunteers. 
 
Study 673-103 evaluated the effect of food on the talazoparib plasma PK following 
administration of a single 0.5 mg dose of talazoparib oral capsule formulation in 18  
healthy volunteers. Food intake (a high-fat, high-calorie meal) had no impact on the AUC 
while reduced the Cmax by 46%. The ratios of adjusted geometric means following 
administration under fed compared to fasted conditions were 97.62% (90% CI: 92.48%, 
103.05%) for AUCinf and 53.88% (90% CI: 48.12%, 60.34%) for Cmax. Consistent with 
findings from the food effect study, population PK analysis using data from Studies 673-
301, 673-201, PRP-001, and PRP-002 showed food intake decreased absorption rate but 
had no impact on the extent of the absorption. The reduction in the rate of absorption 
with food is not expected to be clinically relevant as efficacy is generally driven by total 
exposure. Therefore, talazoparib can be taken without regard of food. 
 
Radioactivity in whole blood versus plasma was approximately 1, indicating that there is 
no preferential distribution of talazoparib into RBC. Based on population PK analysis, the 
talazoparib apparent steady-state volume of distribution (Vss/F) was estimated to be 420 
L, which is significantly greater than total body water (42 L), indicating that talazoparib 
extensively distributes to peripheral tissues. 
  
In vitro experiments with human hepatocytes and liver microsomes indicated that 
talazoparib undergoes minimal hepatic metabolism. Following oral administration of a 
single 1 mg dose of 14C-talazoparib to humans in Study MDV3800-03, no major 
circulating metabolites were identified in plasma, and talazoparib was the only circulating 


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drug-derived entity identified in plasma. No metabolites that individually represented 
more than 10% of the administered dose were recovered in the urine or feces. The 
identified metabolic pathways of talazoparib in humans include: 1) mono-oxidation; 2) 
dehydrogenation; 3) cysteine conjugation of monodesfluorotalazoparib; and 4) 
glucuronide conjugation. 
 
Based on population PK analysis, the talazoparib CL/F was estimated to be 6.45 L/hour. 
In 6 female volunteers with advanced solid tumors given a single oral dose of 14C-
talazoparib (Study MDV3800-03), a mean of 68.7% and 19.7% of the total administered 
radioactive dose was recovered in urine and feces, respectively. Excretion of unchanged 
talazoparib in urine was the major route of elimination accounting for 54.6% of the 
administered dose, while unchanged talazoparib recovered in the feces accounted for 
13.6%. 13 
 
3.3.5. Drug-drug interactions 
 
A Phase 1, open-label, 2-arm, fixed-sequence study (MDV3800-04 [C3441004]) was 
conducted to evaluate the effects of multiple doses of P-glycoprotein (P-gp) inhibitor 
itraconazole and P-gp inducer rifampin on the single-dose PK of talazoparib in volunteers 
with advanced solid tumors. In Arm A, coadministration of multiple daily doses of 
itraconazole 100 mg BID and a single 0.5-mg talazoparib dose increased the area under 
the concentration-time curve from 0 to infinity (AUCinf) and Cmax of talazoparib by 
approximately 56% and 40%, respectively, relative to a single 0.5-mg talazoparib dose 
administered alone. In Arm B, coadministration of multiple daily doses of rifampin 600 
mg and a single 1-mg talazoparib dose increased talazoparib Cmax by approximately 37%, 
whereas AUCinf was not affected relative to a single 1-mg talazoparib dose administered 
alone. Consistent with the findings from the DDI study, population PK analysis indicated 
that concomitant administration of strong P-gp inhibitors with talazoparib increased 
talazoparib exposure by 44.7% relative to talazoparib administered alone. If a strong P-gp 
inhibitor must be coadministered to volunteers, the dose of talazoparib should be reduced 
to 0.75 mg. The overall talazoparib exposures observed when talazoparib was 
administered alone and with rifampin suggested that the effect of rifampin on talazoparib 
exposure in Study MDV3800-04 was minimal. Therefore, no talazoparib dose 
adjustments are recommended upon coadministration with P-gp inducers. 
 
Population PK analysis indicated that coadministration of acid-reducing agents including 
proton-pump inhibitor (PPI), histamine receptor 2 antagonist (H2RA), or other acid-
reducing agents had no significant impact on the absorption of talazoparib. 13 
 
3.3.6. Population pharmacokinetics 
 
The population PK analysis for talazoparib was conducted based on 6207 PK 
observations of 490 volunteers with advanced cancer from 4 clinical trials, Studies PRP-
001, PRP-002, 673-201 and 673-301. Talazoparib PK was well characterized by a 2-
compartment model with first order absorption. In the base model, the estimated 
population mean value for CL/F was 6.45 L/h, for apparent central volume of distribution 


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(V2/F) was 157 L, for apparent peripheral volume of distribution (V3/F) 263 L, for 
apparent inter-compartmental clearance (Q/F) was 9.57 L/hour, for first-order absorption 
rate constant (ka) was 0.991 L/hour, and for lag time for absorption (Tlag) was 0.242 
hour. Thus, the Vss/F was 420 L. 13 
 
3.3.7. Safety profile 
 
Aggregate safety data from 5 open-label, including 1 randomized, company-sponsored 
clinical studies (PRP-001, 673-201, 673-301, MDV3800-13, and MDV3800-14; 
N = 502 volunteers) evaluating talazoparib monotherapy at the proposed dose of 1 
mg/day (Talazoparib 1 mg/day Population) as of 31 January 2018 provide the basis for 
the reported treatment-emergent adverse events (TEAEs). In the ongoing Phase 2, open-
label, extended treatment, safety study (MDV3800-13 [C3441010]), which provides 
access to talazoparib monotherapy for volunteers with solid tumors who were previously 
treated with talazoparib as a single agent or in combination with another agent in 
qualifying originating company-sponsored clinical studies, volunteers received varying 
doses of talazoparib, however, only the 55 volunteers who initiated treatment with 
talazoparib 1 mg/ QD in either the originating or extension study are included in the 
aggregate safety data (Talazoparib 1 mg/day Population). 
 
The overall safety profile of talazoparib is based on pooled data from the 502 volunteers 
who received talazoparib at the proposed dose of 1 mg/day for solid tumors in 673-301, 
673-201, MDV3800-13, PRP-001, and MDV3800-14. This is summarized in Table 2. 13 
 
3.4 
Rationale 
 
Given the effectiveness of PARP inhibitors in mBRCA-associated ovarian cancer, we 
propose a similar feasibility neoadjuvant trial. The study would be coordinated out of the 
Brown University Oncology Group (BrUOG). Our aim would be to determine the 
feasibility of treating 30 volunteers within 2 years. 
 


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Table 2. ADRs Associated With 1 mg/day Talazoparib in Solid Tumors 
 
 
 
 
 
 
 
 
 
 
 
 
4 
VOLUNTEER SELECTION, ELIGIBILITY, AND INELIGIBILTY 
CRITERIA  
 
4.1 
Eligibility Criteria  
 
A volunteer cannot be considered eligible for this study unless ALL of the following 
conditions are met.  
 
1. Volunteers must have clinical and radiographic evidence of newly detected FIGO 
stage II, III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer, 
deemed by a gynecologic oncologist as not amenable to an R0 resection at 
presentation.  
2. Institutional confirmation of Müllerian epithelial adenocarcinoma  
3. Histologic epithelial cell types: high grade serous carcinoma, high grade 
endometrioid carcinoma, or a combination of these. 


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4. Documented mutation in BRCA1 or BRCA2 by genetic or commercial somatic 
testing. Reports will require submission at the time of enrollment.  
5. Measurable disease as defined by RECIST 1.1. Measurable disease is defined as 
at least one lesion that can be accurately measured in at least one dimension 
(longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured 
by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when 
measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when 
measured by CT or MRI.14 
6. Age ≥ 18 
7. Adequate hematologic function determined within 28 days of consent as follows:  
• ANC greater than or equal to 1,500/mcl. NOTE: ANC cannot have been 
induced by granulocyte colony stimulating factors.  
• Platelets greater than or equal to 100,000/mcl  
• Hemoglobin greater than 10 mg/dl (NOTE: While transfusions are 
permitted to achieve baseline hemoglobin level, patients must not have 
transfusion within 14 days prior to obtaining baseline screening labs)  
8. Creatinine Clearance > 15 mL/min. (NOTE: Please see Section 6.2.1 for dosing 
requirements for patients with renal insufficiency) 
 
CrCl = (140- age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/ dL  
  
9. Adequate hepatic function within 14 days prior to registration defined as follows:  
• Bilirubin ≤ 1.5 x ULN  
• ALT and AST < 2.5 x ULN  
• Alkaline phosphatase ≤ 2.5 x ULN 
10. Neurologic function: Neuropathy (sensory and motor) less than or equal to 
CTCAE v5.0 Grade 1. 
11. Ability to swallow and retain oral medication. Adequate gastrointestinal 
absorption with no use of parenteral nutrition within two weeks of trial enrollment 
and no evidence of bowel obstruction. 
12. The volunteer must provide study-specific informed consent prior to study entry. 
 
4.2 
Ineligibility Criteria  
 
Volunteers with any of the following conditions are NOT eligible for this study.  
 
1. Suspected non-gynecologic malignancy, evidenced by tumor markers and/or 
histologic evaluation.  
2. Prior history of other invasive malignancies, with the exception of nonmelanoma 
skin cancer and other specific malignancies as noted in Section 4.2.4 and Section 
4.2.5 are excluded if there is any evidence of other malignancy being present 
within the last three years (2 years for breast cancer, see Section 4.2.4). 
Volunteers are also excluded if their previous cancer treatment contraindicates 
this protocol therapy.  


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3. Prior chemotherapy for any abdominal or pelvic tumor within the last three years 
is excluded. Volunteers may have received prior adjuvant chemotherapy and 
radiotherapy for localized breast cancer, provided that it was completed more than 
2 years prior to registration, the volunteer remains free of recurrent or metastatic 
disease and hormonal therapy has been discontinued.  
4. Prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic 
cavity within the last three years are excluded. Prior radiation for localized cancer 
of the head and neck or skin is permitted, provided that it was completed more 
than three years prior to registration, and the volunteer remains free of recurrent 
or metastatic disease. 
5. Synchronous primary endometrial cancer, or a past history of primary endometrial 
cancer, unless all of the following conditions are met: Stage not greater than I-A, 
grade 1 or 2, no more than superficial myometrial invasion, without vascular or 
lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell 
or other FIGO grade 3 lesions. 
6. Severe, active co-morbidity defined as follows:  
• Chronic or current active infectious disease requiring systemic antibiotics, 
antifungal or antiviral treatment  
• Known brain or central nervous system metastases or history of 
uncontrolled seizures  
• Clinically significant cardiac disease including unstable angina, acute 
myocardial infarction within 6 months from enrollment, New York Heart 
Association Class III or IV congestive heart failure, and serious 
arrhythmia requiring medication (this does not include asymptomatic atrial 
fibrillation with controlled ventricular rate).  
• Partial or complete gastrointestinal obstruction  
7. Volunteers who are not candidates for major abdominal surgery due to known 
medical comorbidities. 
8. Volunteers with any condition that in the judgment of the investigator would 
jeopardize safety or volunteer compliance with the protocol.  
9. Concurrent anticancer therapy (e.g. chemotherapy, radiation therapy, biologic 
therapy, immunotherapy, hormonal therapy, investigational therapy). 
10. Receipt of an investigational study drug for any indication within 30 days or 5 
half-lives (whichever is longer) prior to Day 1 of protocol therapy. 
11. Prior exposure to a PARP inhibitor. 
12. People of child-bearing potential (WOCB). This includes:  
• Any volunteer who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who 
is not postmenopausal. Menopause is defined clinically as 12-month 
amenorrhea in a woman over 45 in the absence of other biological or 
physiological causes.  
• Volunteers who are pregnant or nursing. Volunteers must agree to use 
adequate contraception (hormonal or barrier method of birth control; 
abstinence) prior to study entry, for the duration of study participation, and 
for at least 7 months after completing therapy.  


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People with an intact uterus and ovaries must have a screening negative serum or 
urine pregnancy test within 14 days of registration. A second pregnancy test must be 
done within 24 hours prior to the start of the first cycle of study treatment 
 
13. Potent P-gp inhibitors that result in ≥ 2-fold increase in the exposure of an in vivo 
probe P-gp substrate, including: amiodarone, carvedilol, clarithromycin, 
cobicistat, dronedarone, erythromycin, glecaprevir/pibrentasvir, indinavir, 
itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, 
ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, telaprevir, 
tipranavir, valspodar and verapamil. More instruction available at:  
https://www.druginteractionsolutions.org/ and https://www.fda.gov/drugs/drug-
interactions-labeling/drug-development-and-drug-interactions-table-substrates-
inhibitors-and-inducers#table5-2. 
 
4.3 
Inclusion of Gender, Racial, and Sexual Minorities 
 
All volunteers born with ovaries are eligible for this trial.  
 
5 
REGISTRATION PROCEDURES 
 
All volunteers will be registered through the Brown University Oncology Research 
Group Central Office. Eligibility Checklist with supporting documentation, On Study 
Form and the signed Volunteer Consent Form must be emailed to the BrUOG Central 
Office, BrUOG@brown.edu, at the time of registration and prior to volunteer treatment. 
 
Details of patient’s study participation should be documented in clinic/file notes. This 
project will leverage the Lifespan REDCap instance for making electronic health data 
accessible for research purposes. REDCap was developed by Vanderbilt University with 
collaboration from a consortium of institutional partners as a software toolset and 
workflow methodology for electronic collection and management of research and clinical 
trial data.15 The REDCap platform is a secure, web-based application flexible enough to 
be used for a variety of types of research, provides an intuitive interface for users to enter 
data, and enforces real time validation rules (with automated data type and range checks) 
at the time of entry. This platform provides an intuitive data manipulation interface, 
custom reporting capabilities, audit trail functionality, and real-time data 
monitoring/querying of participant records. REDCap has multiple data export options to 
common statistical packages (SPSS, SAS, Stata, R/S-Plus). The investigator will 
electronically sign the REDCap case reports prior to DSMB review and at the end of 
follow-up to indicate that, to his/her knowledge, they are complete and accurate. 
 
Sites are to be sure that elements to support all inclusion and exclusion criteria are 
submitted and that all assessments from the schedule of evaluations (Section 9) are 
submitted for registration. 
 


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This protocol will allow for enrollment of patients remotely. All patients will require a 
signed informed consent and that visit will be conducted by a member of the Research 
Team remotely via telehealth according to institutional procedures. For patients 
undergoing protocol treatment and not able to travel to the Investigator’s institution, data 
will be collected by the Research Team using locally obtained data.  
 
 
6 
TREATMENT PLAN 
 
6.1 
Summary of the treatment plan 
 
Following consent and registration, volunteers will take talazoparib monotherapy as 1 mg 
capsule orally on a daily basis for three cycles, defined as a 21-day period, prior to 
surgery. Please see Section 6.2.1 dosing for patients with baseline moderate to severe 
renal impairment and those taking a p-gp inhibitor. Volunteers will continue treatment to 
complete three cycles, unless disease progression or unacceptable toxicity occurs. 
 
Volunteers who complete neoadjuvant treatment with talazoparib should undergo 
surgical cytoreduction within three weeks of their last dose of talazoparib. The procedure 
for cytoreduction will be left to the discretion of a specialist-trained gynecologic 
oncologist. Specifically, Heated Intraperitoneal Chemotherapy (HIPEC) or the placement 
of an intraperitoneal (IP) port will be allowed as per Institutional standards of care in the 
management of newly diagnosed ovarian cancer. All volunteers should then undergo 
standard of care adjuvant therapy using carboplatin and paclitaxel. While not mandated 
per protocol, we suggest carboplatin and paclitaxel every 3 weeks for six cycles. The 
exact regimen will be left to the treating investigator. In the case of a volunteer who has 
no evidence of residual disease at surgery (i.e., achieves a pathologic complete 
remission), the option to forego chemotherapy and continue on single agent talazoparib 
must be discussed with the PI and coincide with BrUOG’s procedures. 
 
For volunteers, who agree to continue talazoparib as maintenance therapy, treatment 
should begin three weeks (+/- 2 weeks) from the end of adjuvant chemotherapy or after 
cytoreductive surgery alone (based on the above paragraph), but not before hematologic 
recovery has occurred and maintenance initiation criteria are met. Each maintenance 
talazoparib cycle will be 21 days for two years. Follow-up during the maintenance phase 
will be required on D1 of each cycle for the first six months. Patients who are otherwise 
tolerating treatment will then be seen every third cycle thereafter.  
 
 
6.2 
Talazoparib 
 
6.2.1. 
Dosing 
 
Talazoparib will be provided by Pfizer as capsules to be taken daily (24 hours apart) 
with or without food. Talazoparib capsules must be swallowed whole and not 
dissolved or opened. The starting dose will be 1mg taken orally daily (see below for 


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starting doses for patients with renal impairment and those taking a p-gp inhibitor).  
 
6.2.2. 
Modifications for renal insufficiency  
 
For patients with renal insufficiency, the starting dose of Talazoparib will be reduced 
as follows: 
Creatinine Clearance (mL/min) 
Starting dose (mg) 
30-59 mL/min 
0.75 
15-29 
0.50 
 
6.2.3. 
Drug Product, Safety and Handling 
 
Talazoparib is supplied by Pfizer as capsules in strengths of 0.25 mg, and 1.0 mg. The 
drug product is stored at room temperature (15°C–30°C; 59°F–86°F) or per approved 
local label. Capsules are provided as 0.25 mg, opaque white, size 4; and 1 mg, opaque 
flesh (light pink), size 4 capsules in high-density polyethylene (HDPE) bottles, with heat 
induction-sealed closures, containing 30 drug product capsules of a single strength. 
 
Talazoparib is considered a cytotoxic and clastogenic agent; precautions regarding 
appropriate secure storage and handling must be used by healthcare professionals, 
including personal protective clothing, disposable gloves, and equipment. Volunteers 
should be advised that oral anticancer agents are toxic substances and that caregivers 
(other than the volunteer) should always use gloves when handling the capsules.  
 
6.2.4. 
Missing dose 
 
If the volunteer misses or skips a dose for any reason, it should be taken provided it is 
within 2 hours of the planned dose. Any missing or skipped dose not taken within this 
window should not be taken and the next prescribed dose should be taken at the usual 
time. 
 
6.2.5. 
Dose modifications 
 
The following tables will be utilized for dose modifications due to toxicities. For patients 
with renal dysfunction and starting at a lower dose level at baseline, dose reduction is 
allowable up to 0.25mg daily. 
 
 
Dose Level 
Dose 
Starting  
1 mg (1 capsule) daily 
DL-1 
0.75 mg (3 0.25 mg capsules) daily 
DL-2 
0.50 mg (2 0.25 mg capsules) daily 
DL-3 
0.25 mg (1 0.25 mg capsule) daily 
DL-4 
None. Discontinue protocol treatment 


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Toxicity 
 
Parameter 
Hold Talazoparib until: 
Resume dose level 
Hemoglobin  
≥9 mg/dL 
Resume at reduced dose 
level 
Platelet  
≥75,000/μL 
ANC 
≥1,000/μL 
Clinically Significant G3 
or G4 Non-hematologic 
toxicity 
≤G1 
Resume at reduced dose 
level 
 
NOTES: 
 
1. No dose modifications are indicated based on: volunteer’s age, race, body 
weight.  
2. No dose adjustment is required for volunteers with mild hepatic impairment (total 
bilirubin ≤1 × ULN and AST >ULN, or total bilirubin >1.0 to 1.5 × ULN and any 
AST).  
3. No dose adjustment is required for volunteers with mild renal impairment (60 
mL/min ≤CrCl < 90 mL/min). HOWEVER: 
a. For moderate renal impairment (30 mL/min ≤CrCl < 60 mL/min), the 
recommended dose of talazoparib is 0.75 mg QD.  
b. For severe renal impairment (15 mL/min ≤ CrCL < 30 mL/min), the 
recommended dose of talazoparib is 0.5 mg once daily.  
4. The maximal delay of treatment is six weeks. Volunteers who hold study drug 
beyond six weeks will stop protocol treatment.  
 
6.2.6. 
Contraindications 
 
Talazoparib is contraindicated in volunteers with known hypersensitivity to talazoparib or 
any of the excipients. 
 
6.2.7. 
Special warnings and precautions for use 
 
6.2.7.1. 
Myelosuppression 
 
Myelosuppression consisting of anemia, leukopenia/neutropenia, and/or 
thrombocytopenia, has been reported in volunteers treated with talazoparib. Talazoparib 
maintenance should not be initiated until volunteers have recovered from hematological 
toxicity caused by previous therapy (≤ Grade 1). Volunteers will be routinely monitored 
for hematology parameters and signs and symptoms associated with anemia, 
leukopenia/neutropenia, and/or thrombocytopenia. If any of these events occur, dose 
modifications will be instituted as discussed in Section 6.2.4. Supportive care with or 
without blood and/or platelet transfusions may be used as appropriate. 


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6.2.7.2. 
Myelodysplastic syndrome/Acute Myeloid Leukemia 
 
MDS/AML have been reported in volunteers who received PARP inhibitors. Overall, 
MDS/AML has been reported in < 1% solid tumor volunteers treated with talazoparib in 
clinical studies. Potential contributing factors for the development of MDS/AML include 
previous platinum-containing chemotherapy, other DNA damaging agents or 
radiotherapy. Complete blood counts should be obtained at baseline and monitored 
monthly for signs of hematologic toxicity during treatment. If MDS/AML is confirmed, 
talazoparib should be discontinued. 
 
6.2.7.3. 
Embryo-Fetal Toxicity 
 
Studies in animals have shown embryo-fetal toxicity and talazoparib was clastogenic in 
in vitro and in in vivo assays. Talazoparib should not be given to pregnant volunteers or 
those who plan to become pregnant during treatment. People of childbearing potential 
should be advised to avoid becoming pregnant while receiving talazoparib. Talazoparib 
may cause fetal harm when administered to a pregnant volunteer. A highly effective 
method of contraception is required for volunteers during treatment with talazoparib, and 
for at least 7 months after completing therapy.  
 
6.2.7.4. 
Drug-Drug interactions 
 
Agents that may affect talazoparib plasma concentrations 
 
Effect of P-gp inhibitors (see Exclusion criteria for list - https://www.fda.gov/drugs/drug-
interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-
and-inducers#table5-2.) 
 
Data from a drug-drug interaction study in volunteers with advanced solid tumors 
indicated that coadministration of multiple daily doses of a P-gp inhibitor, itraconazole 
100 mg twice daily with a single 0.5 mg talazoparib dose increased talazoparib total 
exposure (AUCinf) and peak concentration (Cmax) by approximately 56% and 40%, 
respectively, relative to a single 0.5 mg talazoparib dose administered alone. 
 
Population PK analysis has shown that concomitant use of potent P-gp inhibitors (known 
to increase AUC of in vivo P-gp probe substrates by ≥2 fold) with talazoparib increased 
talazoparib exposure by 44.7%, relative to talazoparib given alone.  
 
Volunteers taking any of these agents should consider discontinuation of agents prior to 
start of therapy. If not an option, volunteers will begin on a dose of 0.75 mg/daily. 
 
Effect of P-gp inducers  
 


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Data from a drug-drug interaction study in volunteers with advanced solid tumors 
indicated that co-administration of a P-gp inducer (rifampin 600 mg once daily) with a 
single 1 mg talazoparib dose increased talazoparib Cmax by 37% with no effect on 
talazoparib exposure. 
 
Effect of BCRP inhibitors 
 
Examples of agents: These include, but are not limited to: curcumin, cyclosporine, and 
elacridar [GF120918]). 
 
The effect of BCRP inhibitors on PK of talazoparib has not been studied. Concomitant 
use of strong BCRP inhibitors should be avoided. If co-administration of strong BCRP 
inhibitors cannot be avoided, volunteer should be monitored for potential increased 
adverse reactions. 
 
Effect of acid-reducing agents 
 
Population PK analysis indicates that co-administration of acid-reducing agents including 
proton pump inhibitors (PPI), histamine receptor 2 antagonists (H2RA), or other acid-
reducing agents had no significant impact on the absorption of talazoparib. 13 
 
6.2.7.5. 
Fertility 
 
There is no information on fertility in volunteers. Based on non-clinical findings in testes 
and ovary, male and female fertility may be compromised by treatment with talazoparib. 
 
6.2.7.6. 
People of Childbearing Potential/ Pregnancy 
 
There are no data from the use of talazoparib in pregnant volunteers. Studies in animals 
have shown embryo-fetal toxicity. Talazoparib may cause fetal harm when administered 
to a pregnant volunteer. Talazoparib is not recommended during pregnancy or for people 
of childbearing potential not using contraception. 13 
 
People of childbearing potential should not become pregnant while receiving talazoparib 
and should not be pregnant at the beginning of treatment. A pregnancy test should be 
performed on all people of child bearing potential prior to treatment.  
 
A highly effective method of contraception is required for volunteers during treatment 
with talazoparib, and for at least 7 months after completing therapy. 
 
6.2.7.7. 
Lactation 
 
It is unknown whether talazoparib is excreted in human breast milk. A risk to 
newborns/infants cannot be excluded and therefore breastfeeding is not recommended 
during treatment with talazoparib and for at least 1 month after the final dose. 
 


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6.3 
Pre-treatment criteria for Talazoparib 
 
6.3.1. 
Day one of Cycle 1 (Neoadjuvant treatment only) 
 
If screening labs are performed greater than 14 days prior to Cycle 1 Day 1, labs must be 
repeated on Cycle 1 Day 1. The volunteer may not start on study treatment until Cycle 1 
Day 1 labs meet eligibility criteria. If screening labs are performed within 14 days prior 
to Cycle 1 Day 1, and meet eligibility criteria, labs do not need to be repeated on Cycle 1 
Day 1 unless the investigator believes they are likely to have changed significantly. 
 
6.3.2. 
Subsequent cycles (Neoadjuvant talazoparib and maintenance therapy) 
 
All treatment related toxicities- heme or non-heme- must resolve to <grade 1 or to 
baseline prior to a volunteer initiating a new cycle. Exceptions to this will be for weight 
loss/gain and alopecia and labs deemed not to be clinically significant by the investigator. 
 
6.4 
Criteria for discontinuation of protocol treatment 
 
Whether to continue talazoparib (either in the neoadjuvant setting OR during the optional 
maintenance setting) will depend on individual response, evidence of disease progression 
and tolerance. In the absence of treatment delays due to adverse event(s), treatment will 
continue unless one of the following criteria applies: 
 
• Disease progression.  
• 
Intercurrent illness that prevents further administration of treatment. 
• 
Unacceptable adverse event(s). 
• 
Volunteer demonstrates an inability or unwillingness to comply with the oral 
medication regimen and/or documentation requirements. 
• 
Volunteer decides to withdraw from the protocol therapy. 
• 
General or specific changes in the volunteer’s condition renders her unacceptable 
for further treatment in the judgment of the treating investigator  
• 
Any Grade 4 drug-related adverse event or laboratory abnormality, except for the 
following events:  
• 
Grade 4 neutropenia ≤ 7 days 
• 
Grade 4 lymphopenia or leukopenia 
• 
isolated Grade 4 lab abnormalities, including hepatic function, renal 
function, and/or electrolyte imbalances not associated with clinical 
sequelae and are corrected with supplementation/appropriate 
management. 
• 
Any treatment delay resulting in no dosing for > 6 weeks 
• 
Any adverse event, laboratory abnormality, or intercurrent illness which, in the 
judgment of the Investigator, presents a substantial clinical risk to the volunteer 
with continued dosing. 
 
Participants will be removed from the protocol therapy when any of these criteria 
apply.  The reason for removal from protocol therapy, and the date the participant was 


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removed, must be documented in the case report form (CRF). Alternative care options 
will be discussed with the participant. 
 
In the event of unusual or life-threatening complications, treating investigators must 
immediately notify BrUOG. 
 
6.5 
General concomitant medication and supportive care guidelines 
 
All supportive therapy for optimal medical care will be given during the study period at 
the discretion of the attending physician(s) within the parameters of the protocol and 
documented source documents as concomitant medication. 
 
6.5.1. 
Permitted supportive/ancillary care and concomitant medications 
 
• Analgesics 
• Antibiotics 
• Anticonvulsants 
• Antiemetics 
• Anticoagulants 
• Antihistamines  
• Corticosteroids +/- mineralocorticoid component  
• Hydration 
• Nutritional supplementation 
 
6.5.2. 
Prohibited therapies 
 
None 
 
7 
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS 
 
7.1 
Serious Adverse Events Reported from Clinical Trials 
 
The safety profile of Talazoparib is reviewed in Section 3.3.7. The Reference Safety 
Information (RSI) will be used for the assessment of expectedness of serious ADRs 
reported on this trial and is noted below. The RSI includes only the AEs that have been 
previously reported more than once as serious and treatment related (ie, serious adverse 
reactions [SARs]) in talazoparib clinical trials and where, after a thorough assessment by 
the sponsor, reasonable evidence of a causal relationship between the event and the 
investigational medicinal product exists. 13 
 
Fatal and life-threatening SARs are considered unexpected. Frequency categories are 
defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 
<1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). 
 
 


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7.1.1. 
Adverse event characteristics 
 
This study will utilize the descriptions and grading scales found in the NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 for grading all adverse 
events. All appropriate treatment areas should have access to a copy of the CTCAE 
version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web 
site (http://ctep.cancer.gov).  
 
An Adverse Event (AE) is defined as any untoward medical occurrence in a volunteer or 
clinical investigation volunteer administered a pharmaceutical product and that does not 
necessarily have to 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 Talazoparib whether or not 
considered related to Talazoparib. This includes any newly occurring event or previous 
condition that has increased in severity or frequency since the administration of drug. 
 
During clinical trials, adverse events can be spontaneously reported or elicited during 
open-ended questioning, examination, or evaluation of a volunteer. (In order to prevent 
reporting bias, volunteers should not be questioned regarding the specific occurrence of 
one or more adverse events.) 
 
Adverse events (AEs) will be recorded in the case report form for the duration of the trial, 
regardless of whether or not the event(s) are considered related to trial medication. All 
AEs considered related to trial medication will be followed until resolution even if this 
occurs post-trial. 
 
7.1.2. 
Definitions 
 
An adverse event is any new, undesirable medical experience or change of an existing 
condition that occurs during or after treatment, whether or not considered product-related. 
 
7.1.2.1. 
Attribution of the AE 
 
The following will be used to define attribution to study drug:  


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o Definite – The AE is clearly related to the study treatment. 
o Probable – The AE is likely related to the study treatment. 
o Possible – The AE may be related to the study treatment. 
o Unlikely – The AE is doubtfully related to the study treatment. 
o Unrelated – The AE is clearly NOT related to the study treatment. 
 
Suspected adverse reaction: BrUOG, for the sponsor-investigator, is required to report 
in an IND safety report any suspected reaction to the study treatment that is both 
serious and unexpected.  
 
As per 21 CFR 312.32 (a), the FDA has defined a suspected adverse reaction as any 
adverse event where there is reasonable possibility that the drug may have caused the 
adverse event. A reasonable possibility means there is evidence suggesting a causal 
relationship between the drug and the adverse event.  
 
A suspected adverse reaction outlines the possibility of the causal relationship 
between the event and the drug, whereas an adverse reaction means the drug caused 
the event.  
 
7.1.2.2. 
Serious adverse event 
 
An adverse event occurring at any dose that results in any of the following outcomes 
(CFR 312.32): 
• 
death 
• 
is life-threatening  
• 
involunteer hospitalization or prolongation of existing hospitalization 
excluding those for study drug administration, transfusional support, 
disease staging/re-staging procedures, concomitant radiotherapy, 
thoracentesis / paracentesis, or placement of an indwelling catheter, unless 
associated with other serious events. 
• 
persistent or significant disability or incapacity, 
• 
congenital anomaly / birth defect.  
 
The definition of serious adverse event (experience) also includes important medical 
event. Medical and scientific judgment should be exercised in deciding whether 
expedited reporting is appropriate in other situations, such as important medical 
events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the volunteer or may require intervention to 
prevent one of the other outcomes listed in the definition above.  These should also 
usually be considered serious.  Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; or development of drug dependency 
or drug abuse. A new diagnosis of cancer during the course of treatment should be 
considered an important medical event. 
 
Unexpected adverse event 


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An adverse event that is not mentioned in the Investigator's Brochure or package 
insert or the specificity or severity of which is not consistent with the investigator's 
brochure or package insert. 
 
Life-threatening 
Any adverse drug experience that places the volunteer or volunteer, in the view of the 
investigator, at immediate risk of death from the reaction as it occurred.  It does not 
include a reaction that, had it occurred in a more severe form, might have caused 
death. 
 
NOTE: The following hospitalizations are not considered SAEs: 
• a visit to the emergency room or other hospital department < 24 hours, 
that does not result in admission (unless considered “important medical 
event” or event life threatening)  
• elective surgery, planned prior to signing consent and which would have 
been documented to BrUOG at time of registration (otherwise it will be a 
SAE) admissions as per protocol for a planned medical/surgical procedure 
per study 
• routine health assessment requiring admission for baseline/trending of 
health status (ie, routine colonoscopy)  
• medical/surgical admission for purpose other than remedying ill health 
state and was planned prior to entry into the study. Appropriate 
documentation is required in these cases and which would have been 
documented to BrUOG at time of registration 
• admission encountered for another life circumstance that carries no 
bearing on health status and requires no medical/surgical intervention (ie, 
lack of housing, economic inadequacy, care-giver respite, family 
circumstances, administrative) 
 
7.2 
Monitoring of Adverse Events and Period of Observation 
Adverse events, both serious and non-serious, and deaths that occur during the 
volunteer’s study participation will be recorded in the source documents. 
 
7.3 
BrUOG Adverse Event Reporting Requirements 
 
Investigators are required by Federal Regulation to report adverse drug reactions. 
Questions regarding drugs as used in this study should be directed to the Brown 
University Oncology Research Group (BrUOG) Central Office, Phone: (401) 863-3000 
Fax (401) 863-3820, which will in turn notify the Principal Investigator.  
 
All adverse events and special reporting situations, whether serious or non-serious, 
related or unrelated, will be reported from the time a signed and dated ICF is obtained 
until 30 days after the last treatment (whether that be during neoadjuvant, on standard 
chemotherapy, or during maintenance), or until the volunteer withdraws consent from 


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study participation (declines participation) or at the time volunteer does not meet 
eligibility criteria, whichever occurs first. 
 
7.3.1. 
Pregnancies 
 
Pregnancies occurring while the volunteer is on study drug or within 30 days (+1 
week) after the volunteer’s last dose of study drug are considered expedited 
reportable events.  If the volunteer is on study drug, it is to be discontinued 
immediately.  The pregnancy must be reported to the Brown University Oncology 
Research Group, by the site, immediately (within 24 hours of the site being made 
aware), via a 3500A MedWatch form (site to submit to BrUOG), and BrUOG will in 
turn report to Pfizer immediately (within 1 working day and once in receipt of the site 
submitted SAE form). Pregnancies and suspected pregnancies (including a positive 
pregnancy test regardless of age or disease state) of a volunteer occurring while they 
are on study drug or within 30 days (+1 week) of the volunteer’s last dose of 
talazoparib are considered immediately reportable events. Study drug treatment is to 
be discontinued immediately. The pregnancy, suspected pregnancy, or positive 
pregnancy test must be reported to Pfizer immediately by facsimile, email, or other 
appropriate method. 
 
All neonatal deaths that occur within 30 days of birth should be reported, without 
regard to causality, as SAEs.  In addition, any infant death after 30 days that the 
Investigator suspects to be related to the in-utero exposure to the study drug should 
also be reported. In the case of a live “normal” birth, Pfizer should be advised as soon 
as the information is available (BrUOG will advise Pfizer once information is 
submitted to BrUOG). 
 
7.4 
Serious Adverse Event Reporting Procedures 
 
The principal investigator (or his designee) has the obligation to report all serious adverse 
events to the Brown University Oncology Research Group’s (BrUOG) office who in 
return will report to the FDA, Pfizer, and all sites participating in the trial.  All SAE 
reports will be forwarded to Pfizer by BrUOG. All events must be reported by the 
investigator utilizing the Form FDA 3500A (MedWatch Form).  Sites must alert BrUOG 
to SAEs within 24 hours of being made aware of the event via phone or email, and the 
site will have 5 business days (from when site was made aware of the event) to submit 
formal signed report via the 3500A. BrUOG will then alert Pfizer within 1 business day 
of being in receipt of the signed MedWatch report. 
 
BrUOG will submit a SAE memo and MedWatch 3500A to the FDA within the reporting 
time frames. 
 
The initial report must be as complete as possible, including an assessment of the causal 
relationship between the event and the investigational product(s), if available.  
Information not available at the time of the initial report (e.g., an end date for the adverse 


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event or laboratory values received after the report) must be documented on a follow-up 
report.   
 
A final report to document discharge from hospital (or end of important medical event) is 
required.   
 
All deaths during treatment or within 30 days following completion of active protocol 
treatment must be formally reported to BrUOG within 5 business days of being made 
aware of the event or as soon as the investigator is made aware of the event. If the death 
is thought to be related to the study drug, deaths must be reported to BrUOG within 24 
hours of the investigator being made aware of the event. 
 
All adverse events and special reporting situations, whether serious or non-serious, 
related or unrelated, will be reported from the time a signed and dated ICF is obtained 
until 30 days after the last dose of talazoparib, or until the volunteer withdraws consent 
from study participation (declines participation) or at the time volunteer does not meet 
eligibility criteria, whichever occurs first. 
 
Serious adverse events occurring more than 30 days (+1 week) after study 
discontinuation need only be reported if a relationship to talazoparib is suspected.  
 
7.4.1. 
Types of report and guidelines: 
 
Telephone report:  For SAE’s contact the BrUOG office within 24 hours of learning 
of a SAE. For SAE notification: (initial and follow-up) contact BrUOG Central 
Office (401) 863-3000 or via email, BrUOG@brown.edu with a 24- hour notice prior 
to submitting a SAE report. 
 
Written report: Send the signed MedWatch 3500A form within 5 business days of 
being made aware of the event to the BrUOG Central Office by email. For Follow-up 
reports, please submit the signed MedWatch 3500A when new information has 
become available and the event can be closed out. 
 
Brown University Oncology Research Group 
Phone: (401) 863-3000, Fax: (401) 863-3820 
Emails: BrUOG@brown.edu 
 
All deaths during treatment or within 30 days following completion of active protocol 
treatment must be reported within 5 business days (from when site was made aware 
of the event) or as soon as the investigator is made aware of the event. If the death is 
thought to be related to talazoparib, deaths must be reported to BrUOG within 24 
hours of the investigator being made aware of the event. SAEs post 30 days since 
last dose of drug (+1 week) that are thought to be possibly related to talazoparib 
must be reported to BrUOG within the 5-business day time frame noted above.  
 
MedWatch 3500A Reporting Guidelines 


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In addition to completing appropriate patient demographic and suspect medication 
information, the report should include the following information within the Event 
Description (section 5) of the MedWatch 3500A form: 
 
• Treatment regimen (dosing frequency, combination therapy) 
• Protocol description (and number, if assigned) 
• Description of event, severity, treatment, and outcome, if known 
• Action taken with talazoparib as a result of the SAE and expectedness (based 
on the IB and consent) 
• Supportive laboratory results and diagnostics 
• Investigator’s assessment of the relationship of the adverse event to talazoparib  
• Site to be clear to outline which events are being reports as serious 
• Must be typed 
• A final report to document discharge from hospital (or resolution of 
important medical event) is required.   
 
Follow-up information:   
 
For any follow-up SAE report, submit a new MedWatch 3500A report; do not 
resubmit the initial report with any additions. The follow-up report must be submitted 
to BrUOG with subject identifiers (subject number, initials, and date of birth), 
protocol description, suspect drug, a brief summary of previously reported SAE 
information, and any new information, including modification of prior events, 
causality, new serious events, discharge date, etc.   
 
A final report documenting discharge date from the hospital is required.  
 
The principal Investigator is required to notify his/her Institutional Review Board 
(IRB) of a serious adverse event according to institutional policy.   
 
7.5 
BrUOG Responsibility regarding reporting 
 
The sponsor-investigator by way of BrUOG, the sponsor representative and central 
coordinating office, is required to promptly review all information relevant to the safety 
of the drug (21 CFR 312.32(b)).  
 
Safety Reporting for IND Holders 
In accordance with 21 CFR 212.32, Sponsor-Investigator of the study conducted under an 
IND must comply with following safety-reporting requirements:  
 
The BrUOG Central Office will notify all drug reaction reports to the FDA, the Principal 
Investigator, and the participating sites (who will in turn notify their local IRBs) as soon 
as possible but no later than 15 calendar days after initial receipt of the signed 
information, submitted to BrUOG by the site, as per regulatory requirements.  


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BrUOG, for the sponsor-investigator, is required to report in an IND safety report any 
suspected reaction to the study treatment that is both serious and unexpected (21 CFR 
312.32 (c)(1)(i)). It is required that events that are suspected, serious and unexpected, be 
reported to the FDA via an IND safety report. 
 
BrUOG will fax reports to the FDA for IND Safety Reports: to the CDER DOP1 fax 
number at: (301)-796-9845 SAEs will be reported as an amendment to the IND (if 
applicable) within 15 days of sponsor notification. The FDA will all receive a 
simultaneous copy via facsimile of all adverse events filed with the FDA (which will be 
sent to the division fax). A copy of the form will be kept by the BrUOG Central Office.    
 
• “IND safety report” for 15-day reports  
•  “Follow-up IND safety report” for follow-up information   
• “7-day IND safety report” for unexpected fatal or life-threatening adverse reaction 
reports 
 
 
Fax: For this IND study a SAE will be sent to Center Drug Evaluation Division fax 
line that has responsibility for review of IND): CDER DOP1: (301)-796-9845 
 
Mail: For IND studies BrUOG will send the SAE as an amendment to the IND as 
well. 
 
All SAEs that are serious and reasonably or probably related to the use of 
talazoparib will also be sent to Pfizer within 1 business day of being in receipt of the 
complete signed site submitted documentation. 
 
7.6 
IND Annual Reports (if IND study only) 
 
If the FDA has granted an IND number, it is a requirement of 21 CFR 312.33, that an 
annual report is provided to the FDA within 60-days of the IND anniversary date.  21 
CRF 312.33 provides the data elements that are to be submitted in the report.  The 
Annual Report will be filed in the study's Regulatory Binder, and a copy provided to 
Pfizer as a supporter of this study. 
 
7.7 
Adverse event updates/IND safety reports 
 
Pfizer shall notify the Brown University Oncology Research Group (BrUOG) via an IND 
Safety Report of the following information: 
 
• Any AE associated with the use of study drug in this study or in other studies that 
is both serious and unexpected. 
• Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or 
carcinogenicity. 


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BrUOG will then notify the sites who shall notify their IRB/EC promptly of these new 
serious and unexpected AE(s) or significant risks to subjects. 
 
8 
 ORDERING TALAZOPARIB 
 
8.1 
Initial orders 
 
The drug supply request form in Global Medical Grants System (GMGS) will be used to for drug 
ordering.  Once the site has been activated by BrUOG and once Pfizer has received all initial 
approval documentation, the drug supply request form will be completed in GMGS. Pfizer’s grant 
administrator receives an automated message regarding the drug request.  
 
8.2 
Resupply 
 
Resupply of drug will be requested via the GMGS.  Please allow for 2-3 weeks for the 
shipment of drug.   
 
8.3 
Drug excursions 
Temperature excursions should be emailed to GCSTempExcursionSupport@pfizer.com and cc 
BrUOG@brown.edu  
 
Storage excursion: 
Include the following in the body of the email for temperature excursions: 
Study number (BrUOG 390) 
Site   
Temperature recorder data of monitoring log showing the date and duration of excursion (data 
should include previous acceptable reading and reading showing return to acceptable conditions) 
 
Shipment excursion: 
Include the following in the body of the email: 
Study number (BrUOG 390) 
Site  
Shipment number 
Temperature recorder data of monitoring log showing the date and duration of excursion (data 
should include previous acceptable reading and reading showing return to acceptable conditions) 
 
 
8.4 
Questions on drug expiration, delayed shipment, etc.  
 
Questions regarding drug expiration or delayed shipment may be directed to Ying 
at ying.zhangying@pfizer.com, waqas.ahmed@pfizer.com, and cc BrUOG@brown.edu. 
 
8.5 
Accountability 
 


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The investigator, or a responsible party designated by the investigator, will maintain a 
careful record of the inventory and disposition of the agent using the NCI Drug 
Accountability Record Form (DARF) or another comparable drug accountability form.   
 
For patients undergoing protocol treatment who are unable to travel to Providence, drug 
accountability will be documented during a telehealth visit. If patients discontinue study 
treatment, all remaining drug will be shipped back to the PI’s Institution for accounting. 
 
 
8.6 
Destruction and return 
 
All opened Talazoparib (full, partially used, and empty) may be destroyed at the site by the 
appropriate site personnel (e.g. Pharmacist; Study Nurse/Coordinator) following local 
environmental requirements and institutional policies. 
 
All destruction of unused drug must be fully documented at the time of destruction on the drug 
accountability log at the time of destruction. 
 
All unused, unopened and rejected supplies will need to be approved by Pfizer for destruction 
prior to any drug being destroyed. BrUOG will obtain Pfizer approval to destroy. Documentation 
of all destruction is required on the drug accountability log. 
 
 
9 
STUDY CALENDAR 
 
9.1 
Pre-Treatment assessments 
The day an assessment (PE, Lab, scan etc.) is performed is considered day 0 for counting. 
 
 
Required for Registration 
Prior to Cycle 1 
Informed consent  
≤28 days 
 
Tissue confirmation 
X 
 
mBRCA confirmation 
X 
 
Concurrent meds 
≤28 days 
≤14 days 
History and Physical exam 
≤28 days 
≤28 days 
Blood pressure, Pulse 
≤28 days 
≤28 days 
Weight and Height (Height only at baseline) 
≤28 days 
≤28 days 
Performance status 
≤28 days 
≤28 days 
CBC w/diff 
≤28 days 
≤14 days 
Serum chemistry* 
≤28 days 
≤14 days 
CA125 
≤28 days 
≤7 days 
HCG**  
≤14 days 
Within 24 hours 
Adverse event evaluation 
≤14 days 
≤14 days 
CT Chest, Abdomen, and Pelvis 
≤28 days 
 
*Electrolytes including BUN, Crea, Ca, and Mg; LFTs including Bilirubin, ALT, AST, Alk Phos, and albumin.  
** Urine or serum in applicable volunteers, per eligibility criteria.  


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9.2 
On-treatment assessments  
 
9.2.1. 
During neoadjuvant treatment. The following table applies to all volunteers 
receiving talazoparib prior to surgery. Volunteers who discontinue talazoparib 
during this period (nine weeks) will be discontinued from the protocol. For patients 
undergoing protocol treatment and not able to travel to the Investigator’s institution, 
data will be collected by the Research Team using locally obtained data.  
 
 
D1 of each cycle1 
(Cycles 1-3) 
Weekly 
End of treatment2 
History and Physical (includes weight, blood 
pressure, heart rate, and ECOG performance status) 
X 
 
X 
CBC with differential 
X 
X 
X 
Chemistries (liver function, renal function)3 
X 
 
X 
CA125 
X 
 
 
Urine pregnancy test4 
X 
 
 
Pill counts 
X5 
 
X 
Concurrent meds 
X 
 
 
Adverse event evaluation 
X 
X 
X 
Tumor measurements6 
 
 
X 
1. One cycle = 21 days. Assessment can be performed within 72 hours of D1. 
2. End of treatment evaluation should occur within 14 days (+/- 7) of C3D21 
3. Electrolytes including BUN, Crea, Ca, and Mg; LFTs including Bilirubin, ALT, AST, Alk Phos, and albumin.  
4. In women of childbearing potential. 
5. Reviewed on D1 of C2 and C3  
6. CT Chest, Abdomen, and Pelvis is required at the end of treatment. Volunteers who discontinue neoadjuvant treatment early 
for whatever reason are encouraged to undergo imaging within 14 days (+/- 7 days) of treatment.  
 
9.2.2. 
Surgery and adjuvant treatment 
 
Volunteers who complete neoadjuvant treatment with talazoparib should undergo 
surgical cytoreduction within three weeks of their last dose of talazoparib. The procedure 
for cytoreduction will be left to the discretion of a board certified gynecologic oncologist. 
Specifically, Heated Intraperitoneal Chemotherapy (HIPEC) or the placement of an 
intraperitoneal (IP) port will be allowed as per Institutional standards of care in the 
management of newly diagnosed ovarian cancer. 
 
The following data will be collected: 
 
• Description of disease burden  
• Cytoreduction status (R0, optimal with microscopic residual, suboptimal, and CR 
Score – Reference 5) 
• Clinical FIGO stage  
• Final pathology (with pathologic stage) 
 
Following surgery, all volunteers should undergo carboplatin and paclitaxel adjuvant 
therapy. However, patients with an optimal cytoreduction and who according to the 
treating physician has had a good response to Talazoparib, and who wish to forego 
adjuvant chemotherapy, may be allowed to do after consultation with the Principal 
Investigator or his designate. The regimen and duration will be determined by the local 
provider. We will plan to collect the following data: 


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• Regimen prescribed (including whether HIPEC was performed) 
• Cycles planned 
• Cycles administered 
• Start and stop dates  
• Adverse events 
 
NOTE: While we will not mandate a specific adjuvant regimen, we will plan to collect 
toxicity data at 21-day intervals.  
 
9.2.3. 
Maintenance therapy 
 
The following data will be collected during maintenance: 
 
 
D1 of each 
cycle1 
(Cycles 1-8) 
D1 of every 3rd 
cycle (Cycles 9 
to 24) 
Weekly2 
Every 3 
months 
End of 
treatment3 
History and Physical (includes weight, blood 
pressure, heart rate, and ECOG performance 
status) 
X 
X 
 
 
X 
CBC with differential 
X 
X 
X 
 
X 
Chemistries (liver function, renal function)4 
X 
X 
 
 
X 
CA125 
X 
X 
 
 
 
Urine pregnancy test5 
X 
X 
 
 
 
Pill counts 
X6 
X6 
 
 
X 
Concurrent meds 
X 
X 
 
 
 
Adverse event evaluation 
X 
X 
X 
 
X 
Tumor measurements7 
 
 
 
X 
X 
1. One cycle = 21 days. Treatment will be administered daily. Assessment can be performed within 72 hours of D1. 
2. Weekly labs will be collected during the first two cycles after which volunteers will not be required to do labs weekly, unless 
recommended by their local investigator.  
3. End of treatment evaluation should occur within 14 days (+/- 7)  
4. Electrolytes including BUN, Crea, Ca, and Mg; LFTs including Bilirubin, ALT, AST, Alk Phos, and albumin.  
5. In women of childbearing potential. 
6. Reviewed on D1 starting with Cycle 2.  
7. CT Chest, Abdomen, and Pelvis are required every three months (+/- 2 weeks) during maintenance and at the end of treatment. 
Volunteers who discontinue talazoparib maintenance treatment early for whatever reason are encouraged to undergo imaging within 
14 days (+/- 7 days) of treatment.  
 
Volunteers who decide not to proceed with maintenance talazoparib will be withdrawn 
from the study and will be followed according to the follow-up schedule in Section 10.  
 
9.2.4. For patients undergoing protocol treatment and not able to travel to the 
Investigator’s institution, data will be collected by the Research Team using locally 
obtained data. 
 
10 ASSESSMENTS IN FOLLOW-UP 
 
Following completion of treatment, all volunteers enrolled will be followed for five years 
from date of registration. The following will be collected:   
 
 
Schedule 


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History and Physical Exam (includes weight, performance status, blood 
pressure) 
X1 
Serum Ca-125 
X1 
Toxicity Assessment2 
X1 
CT Chest, Abdomen, and Pelvis 
Every 3 months3 
Disease Status 
X1 
1. 
Every 3 months (+/- 7 days) for the first 2 years; then every 6 months (+/- 7 days) for the next 3 years until disease 
progression or volunteer initiates a subsequent cancer therapy. 
2. 
Volunteers who discontinue treatment for unacceptable adverse event(s) will be followed until resolution or stabilization of 
the adverse event.  
3. 
Imaging should be performed every 3 months (+/- 3 weeks) in the first three years, and then every 6 months to the fifth 
year. However, they can be repeated any other time if clinically indicated based on symptoms, physical signs or rising CA-125 
levels suggestive of new or progressive disease. 
 
 
11 MEASUREMENT OF EFFECT 
 
11.1 
Antitumor Effect – Solid Tumors 
 
For the purposes of this study, during neoadjuvant therapy, a baseline and end-of-
treatment (pre-surgery) CT Chest, Abdomen, and Pelvis will be performed.  During 
maintenance therapy, CT Chest, Abdomen, and Pelvis will be performed every three 
months (+/- 2 weeks) and at the end of treatment, and in follow-up, CT Chest, Abdomen, 
and Pelvis will be performed every three months (+/- 3 weeks) for the first three years 
and then every 6 months until the fifth year. 
 
Response and progression will be evaluated in this study using the new international 
criteria proposed by the 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. 
 
11.1.1 Definitions 
 
Evaluable for Target Disease response.  Only those participants 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 
target disease response.  These participants will have their response classified 
according to the definitions stated below.  (Note:  Participants who exhibit 
objective disease progression prior to the end of cycle 1 will also be considered 
evaluable.) 
 
Evaluable Non-Target Disease Response.  Participants 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.  


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11.1.2 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 or ≥10 mm with CT scan, MRI, or 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.  
 
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, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, abdominal masses (not followed by 
CT or MRI), and cystic lesions are all considered 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 participant, 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 


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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.  
 
 
11.1.3 Methods for Evaluation of Disease 
 
All measurements should be taken and recorded in metric notation using a ruler, 
calipers, or a digital measurement tool.  For purposes of this trial, all patients are 
to undergo imaging using CT of the chest, abdomen, and pelvis for disease 
assessment and only CTs will be used for disease evaluation. 
 
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.  
 
Conventional CT. This guideline has defined measurability of lesions on CT scan 
based on the assumption that CT thickness is 5mm or less. If CT scans have slice 
thickness greater than 5 mm, the minimum size of a measurable lesion should be 
twice the slice thickness. MRI is also acceptable in certain situations (e.g. for 
body scans).   
 
Clinical lesions. Clinical lesions will only be considered measurable when they 
are superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm in 
diameter as 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.  
 
MRI. The use of MRI cannot be used for disease assessment on the trial. 
 
PET/CT: Not allowed for measurement of disease.  
 
Endoscopy, Laparoscopy. The utilization of these techniques for objective tumor 
evaluation is not permitted.  
 


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Tumor markers. Tumor markers alone will not be used to assess response. If 
markers are initially above the upper normal limit, they must normalize for a 
participant to be considered in complete clinical response.  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]. 
 
11.1.4 Response Criteria RECIST 1.1 
 
11.1.4.1 
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. 
 
11.1.4.2 
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-target lesion(s) and/or 
maintenance of tumor marker level above the normal limits. 
 
Progressive Disease (PD):  Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesions.  Unequivocal 
progression should not normally trump target lesion status.  It must be 
representative of overall disease status change, not a single lesion increase.     
 


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Although a clear progression of “non-target” lesions only is exceptional, the 
opinion of the treating physician should prevail in such circumstances, and the 
progression status should be confirmed at a later time by the review panel (or 
Principal Investigator). 
 
11.1.4.3 
Evaluation of New Lesions 
 
The finding of a new lesion should be unequivocal (i.e. not due to difference 
in scanning technique, imaging modality, or findings thought to represent 
something other than tumor (for example, some ‘new’ bone lesions may be 
simply healing or flare of pre-existing lesions). However, a lesion identified 
on a follow-up scan in an anatomical location that was not scanned at baseline 
is considered new and will indicate PD. If a new lesion is equivocal (because 
of small size etc.), follow-up evaluation will clarify if it truly represents new 
disease and if PD is confirmed, progression should be declared using the date 
of the initial scan on which the lesion was discovered. 
 
11.1.4.4 
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 Participants with Measurable Disease (i.e., Target Disease) 
 
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 


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            accepted as disease progression. 
 
Note:  Participants 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. 
 
11.1.4.5 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, or 
death due to any cause. Participants without events reported are censored at the last 
disease evaluation). 
 
Duration of overall complete response: 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, or death due to any cause. Participants without events 
reported are censored at the last disease evaluation.  
 
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.  
 
Progression-Free Survival 
 
Overall Survival: Overall Survival (OS) is defined as the time from randomization (or 
registration) to death due to any cause, or censored at date last known alive.  
 
Progression-Free Survival: Progression-Free Survival (PFS) is defined as the time from 
randomization (or registration) to the earlier of progression or death due to any cause. 
Participants alive without disease progression are censored at date of last disease 
evaluation. 
 
Time to Progression: Time to Progression (TTP) is defined as the time from 
randomization (or registration) to progression, or censored at date of last disease 
evaluation for those without progression reported. 
 
12 STATISTICAL CONSIDERATIONS 
 
12.1 Primary objectives 
 
The primary objective for this feasibility trial will be to determine if we can enroll 30 
volunteers in to this neoadjuvant PARP inhibitor trial. Given that mBRCA carriers 


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represent less than 15% of all people with newly diagnosed ovarian cancer, it will be 
challenging not only to find this population but to see if they are also comfortable with a 
non-chemotherapy regimen as neoadjuvant treatment. It is also based on the experience 
of Litton and colleagues who sought to enroll a similar cohort with newly diagnosed 
breast cancer.7 
 
In addition to enrolling these volunteers, we aim to define the proportion of volunteers 
completing the planned 9 weeks of treatment without disease progression. For women 
receiving neoadjuvant carboplatin and paclitaxel, the estimated rate of progression on 
treatment is 15%.16 For purposes of this trial, we will adopt a more stringent criterion for 
progression at 10%. As such, if 3 or more volunteers progress during treatment, we will 
declare it non-feasible. 
 
12.2 Secondary objectives 
 
Preliminary effectiveness: We will determine the clinical response of volunteers on this 
trial, determined by standard of care measurements (e.g., CA125 and CT scan). For those 
undergoing surgery, we will also report the rate of optimal cytoreduction and of resection 
to no residual disease (R0).  
 
Safety of neoadjuvant treatment: This will be defined by the aggregate toxicity rate in the 
first seven enrolled volunteers. If 2 or more volunteers experience either a grade 4 
toxicity attributable to the treatment or require a delay in treatment for greater than 4 
weeks due to toxicity, the study will be discontinued. Treatment-related toxicities will be 
summarized by maximum grade and by term using CTCAE v5.0 and reported with 90% 
binomial exact confidence intervals. 
 
 
12.3 Exploratory objectives 
 
For those who undergo interval cytoreduction, we will also determine the effect of 
treatment by CRS. While this was developed for the use of carboplatin and paclitaxel 
treatment for high-grade serous carcinoma, we will report this as well to determine if this 
is a useful measure in this setting. 
 
All volunteers enrolled on this trial will be offered talazoparib maintenance treatment 
following completion of adjuvant chemotherapy. We will measure progression-free 
survival, measured from the start of maintenance therapy. This will be modeled after the 
SOLO-1 trial, where maintenance olaparib significantly extended 3yPFS compared to 
placebo with a Hazard Ratio of 0.3. Based on this HR, using 80% power with an alpha of 
0.05, we estimate that 22 patients would be needed to meet this exploratory objective. By 
enrolling 30 women, we anticipate we will be able to treat 22 to achieve this objective. 
 
 
13 REGULATORY CONSIDERATIONS 
 


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13.1 Good Clinical Practice 
 
The study will be conducted in accordance with the International Conference on 
Harmonisation (ICH) for Good Clinical Practice (GCP) and in the US Code of Federal 
Regulations.  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 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.   
 
13.2 Patient Confidentiality 
 
In order to maintain patient privacy, all data capture records, drug accountability records, 
study reports and communications will identify the patient by initials and the assigned 
patient number.  The investigator will grant monitor(s) and auditor(s) from Pfizer 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. 
 
13.3 Protocol Compliance 
 
The investigator will conduct the study in compliance with the protocol given 
approval/favorable opinion by the IRB/IEC and the appropriate regulatory authority(ies).  
Changes to the protocol will require approval from Pfizer and written IRB/IEC 
approval/favorable opinion prior to implementation, except when the modification is 
needed to eliminate an immediate hazard(s) to patients.  The IRB/IEC 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/IEC.  The investigator will submit all protocol modifications to Pfizer and the 
regulatory authority (ies) in accordance with the governing regulations. Any departures 
from the protocol must be fully documented in the source documents.   
 
13.4 On-site Audits 
 
Regulatory authorities, the IRB and/or Pfizer 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. 
 
13.5 Drug Accountability 
 
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 


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(if applicable), inventory at the site (if applicable), use by each patient, and return to 
Pfizer for disposal of the drug (if applicable and if approved by Pfizer) will be maintained 
by the clinical site.  Accountability records will include dates, quantities, lot numbers, 
expiration dates (if applicable), and patient numbers.   
 
All material containing Talazoparib will be treated and disposed of as hazardous waste in 
accordance with governing regulations. 
 
13.6 Premature Closure of the Study 
 
This study may be prematurely terminated, if in the opinion of the investigator or Pfizer, 
there is sufficient reasonable cause.  Written notification documenting the reason for 
study termination will be provided to the investigator or Pfizer 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 
• Should the study be closed prematurely, all study materials must be returned to 
Pfizer 
 
13.7 Record Retention 
 
The investigator will maintain all study records according to ICH-GCP and applicable 
regulatory requirement(s). The Brown University Oncology Research Group, as 
coordinator of this study, is responsible for ensuring proper conduct of the study with 
regard to protocol adherence and the validity of the data recorded on the case report 
forms. The Principal Investigator (Don Dizon, M.D.) and Brown University Oncology 
Research Group Director of Operations (Roxanne Wood) will monitor this study. The 
case report forms will be monitored against the submitted documents for accuracy, 
completeness, adherence to the protocol and regulatory compliance.  
 
U.S. FDA regulations (21CFR312.62[c] require all records and documents pertaining to 
the conduct of this study and the distribution of investigational drug, including CRFs, 
consents forms, laboratory test results and medication inventory records, must be retained 
by the Principal Investigator for 2 years after marketing application approval. If no 
application is filed, these records must be kept 2 years after the investigation is 
discontinued and the FDA and the applicable local health authorities are notified. Pfizer 
will notify the Principal Investigator if an application is filed.  
 
14 DATA SAFETY AND MONITORING BOARDS 
 
All trials initiated by the Brown University Oncology Research Group (BrUOG) are 


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subject to oversight by the Data Safety Monitoring Board (DSMB).  This board meets 
two times per year with any additional meetings scheduled when needed.  The 
responsibilities are as follows: 
• Familiarize themselves with the research protocol (s)  
• The DSMB reviews trial performance information such as accrual information.   
• Review interim analyses of outcome data and cumulative toxicity data summaries 
to determine whether the trial should continue as originally designed, should be 
changed, or should be terminated based on these data.   
• The DSMB also determines whether and to whom outcome results should be 
released prior to the reporting of study results. 
• All adverse events are reviewed by the committee, with assurances that these have 
been in fact sent for review to all pertinent IRBs. 
• Review of reports of related studies to determine whether the monitored study 
needs to be changed or terminated. 
• Review major proposed modifications to the study prior to their implementation 
(e.g., termination, dropping an arm based on toxicity results or other reported trial 
outcomes, increasing target sample size). 
• Following each DSMB meeting, provide the study leadership with written 
information concerning findings for the trial as a whole related to cumulative 
toxicities observed and any relevant recommendations related to continuing, 
changing, or terminating the trial.  
 
The study leadership will provide information on cumulative toxicities and relevant 
recommendations to the local principal investigators to be shared with their IRB’s. 
 
 
15 PUBLICATION PLAN 
 
The end of the study is the time point at which the last data items are to be reported, or 
after the outcome data are sufficiently mature for analysis, as defined in the section on 
Sample Size, Accrual Rate and Study Duration. It is anticipated that a report will be 
presented in a national or international meeting within 24 months of last patient entered 
on study.  This abstract will meet the requirements of the International Committee of 
Medical Journal Editors. A full report of the outcomes will be made public no later than 
three (3) years after the end of the study.  
 
16 REFERENCES 
 
(1)  Lee, J. Y.; Chung, Y. S.; Na, K.; Kim, H. M.; Park, C. K.; Nam, E. J.; Kim, S.; Kim, 
S. W.; Kim, Y. T.; Kim, H. S. External Validation of Chemotherapy Response 
Score System for Histopathological Assessment of Tumor Regression after 
Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma. J. 
Gynecol. Oncol. 2017, 28 (6), e73. https://doi.org/10.3802/jgo.2017.28.e73. 
(2)  Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2019. CA. Cancer J. Clin. 
2019, 69 (1), 7–34. https://doi.org/10.3322/caac.21551. 


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(3)  Konstantinopoulos, P. A.; Ceccaldi, R.; Shapiro, G. I.; D’Andrea, A. D. 
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability 
of Ovarian Cancer. Cancer Discov. 2015, 5 (11), 1137–1154. 
https://doi.org/10.1158/2159-8290.CD-15-0714. 
(4)  Kehoe, S.; Hook, J.; Nankivell, M.; Jayson, G. C.; Kitchener, H.; Lopes, T.; 
Luesley, D.; Perren, T.; Bannoo, S.; Mascarenhas, M.; Dobbs, S.; Essapen, S.; 
Twigg, J.; Herod, J.; McCluggage, G.; Parmar, M.; Swart, A.-M. Primary 
Chemotherapy versus Primary Surgery for Newly Diagnosed Advanced Ovarian 
Cancer (CHORUS): An Open-Label, Randomised, Controlled, Non-Inferiority 
Trial. Lancet Lond. Engl. 2015, 386 (9990), 249–257. 
https://doi.org/10.1016/S0140-6736(14)62223-6. 
(5)  Vergote, I.; Tropé, C. G.; Amant, F.; Kristensen, G. B.; Ehlen, T.; Johnson, N.; 
Verheijen, R. H. M.; van der Burg, M. E. L.; Lacave, A. J.; Panici, P. B.; Kenter, G. 
G.; Casado, A.; Mendiola, C.; Coens, C.; Verleye, L.; Stuart, G. C. E.; Pecorelli, S.; 
Reed, N. S.; European Organization for Research and Treatment of Cancer-
Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant 
Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer. N. Engl. J. 
Med. 2010, 363 (10), 943–953. https://doi.org/10.1056/NEJMoa0908806. 
(6)  Moore, K.; Colombo, N.; Scambia, G.; Kim, B.-G.; Oaknin, A.; Friedlander, M.; 
Lisyanskaya, A.; Floquet, A.; Leary, A.; Sonke, G. S.; Gourley, C.; Banerjee, S.; 
Oza, A.; González-Martín, A.; Aghajanian, C.; Bradley, W.; Mathews, C.; Liu, J.; 
Lowe, E. S.; Bloomfield, R.; DiSilvestro, P. Maintenance Olaparib in Patients with 
Newly Diagnosed Advanced Ovarian Cancer. N. Engl. J. Med. 2018, 379 (26), 
2495–2505. https://doi.org/10.1056/NEJMoa1810858. 
(7)  Litton, J. K.; Scoggins, M.; Ramirez, D. L.; Murthy, R. K.; Whitman, G. J.; Hess, K. 
R.; Adrada, B. E.; Moulder, S. L.; Barcenas, C. H.; Valero, V.; Gomez, J. S.; 
Mittendorf, E. A.; Thompson, A.; Helgason, T.; Mills, G. B.; Piwnica-Worms, H.; 
Arun, B. K. A Feasibility Study of Neoadjuvant Talazoparib for Operable Breast 
Cancer Patients with a Germline BRCA Mutation Demonstrates Marked Activity. 
NPJ Breast Cancer 2017, 3, 49. https://doi.org/10.1038/s41523-017-0052-4. 
(8)  Mirza, M. R.; Monk, B. J.; Herrstedt, J.; Oza, A. M.; Mahner, S.; Redondo, A.; 
Fabbro, M.; Ledermann, J. A.; Lorusso, D.; Vergote, I.; Ben-Baruch, N. E.; Marth, 
C.; Mądry, R.; Christensen, R. D.; Berek, J. S.; Dørum, A.; Tinker, A. V.; du Bois, 
A.; González-Martín, A.; Follana, P.; Benigno, B.; Rosenberg, P.; Gilbert, L.; 
Rimel, B. J.; Buscema, J.; Balser, J. P.; Agarwal, S.; Matulonis, U. A.; ENGOT-
OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, 
Recurrent Ovarian Cancer. N. Engl. J. Med. 2016, 375 (22), 2154–2164. 
https://doi.org/10.1056/NEJMoa1611310. 
(9)  Pujade-Lauraine, E.; Ledermann, J. A.; Selle, F.; Gebski, V.; Penson, R. T.; Oza, A. 
M.; Korach, J.; Huzarski, T.; Poveda, A.; Pignata, S.; Friedlander, M.; Colombo, N.; 
Harter, P.; Fujiwara, K.; Ray-Coquard, I.; Banerjee, S.; Liu, J.; Lowe, E. S.; 
Bloomfield, R.; Pautier, P.; Korach, J.; Huzarski, T.; Byrski, T.; Pautier, P.; 
Friedlander, M.; Harter, P.; Colombo, N.; Pignata, S.; Scambia, G.; Nicoletto, M.; 
Nussey, F.; Clamp, A.; Penson, R.; Oza, A.; Poveda Velasco, A.; Rodrigues, M.; 
Lotz, J.-P.; Selle, F.; Ray-Coquard, I.; Provencher, D.; Prat Aparicio, A.; Vidal 
Boixader, L.; Scott, C.; Tamura, K.; Yunokawa, M.; Lisyanskaya, A.; Medioni, J.; 


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Pécuchet, N.; Dubot, C.; de la Motte Rouge, T.; Kaminsky, M.-C.; Weber, B.; 
Lortholary, A.; Parkinson, C.; Ledermann, J.; Williams, S.; Banerjee, S.; Cosin, J.; 
Hoffman, J.; Penson, R.; Plante, M.; Covens, A.; Sonke, G.; Joly, F.; Floquet, A.; 
Banerjee, S.; Hirte, H.; Amit, A.; Park-Simon, T.-W.; Matsumoto, K.; Tjulandin, S.; 
Kim, J. H.; Gladieff, L.; Sabbatini, R.; O’Malley, D.; Timmins, P.; Kredentser, D.; 
Laínez Milagro, N.; Barretina Ginesta, M. P.; Tibau Martorell, A.; Gómez de Liaño 
Lista, A.; Ojeda González, B.; Mileshkin, L.; Mandai, M.; Boere, I.; Ottevanger, P.; 
Nam, J.-H.; Filho, E.; Hamizi, S.; Cognetti, F.; Warshal, D.; Dickson-Michelson, E.; 
Kamelle, S.; McKenzie, N.; Rodriguez, G.; Armstrong, D.; Chalas, E.; Celano, P.; 
Behbakht, K.; Davidson, S.; Welch, S.; Helpman, L.; Fishman, A.; Bruchim, I.; 
Sikorska, M.; Słowińska, A.; Rogowski, W.; Bidziński, M.; Śpiewankiewicz, B.; 
Casado Herraez, A.; Mendiola Fernández, C.; Gropp-Meier, M.; Saito, T.; 
Takehara, K.; Enomoto, T.; Watari, H.; Choi, C. H.; Kim, B.-G.; Kim, J. W.; Hegg, 
R.; Vergote, I. Olaparib Tablets as Maintenance Therapy in Patients with Platinum-
Sensitive, Relapsed Ovarian Cancer and a BRCA1/2 Mutation (SOLO2/ENGOT-
Ov21): A Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trial. Lancet 
Oncol. 2017, 18 (9), 1274–1284. https://doi.org/10.1016/S1470-2045(17)30469-2. 
(10)  Kim, G.; Ison, G.; McKee, A. E.; Zhang, H.; Tang, S.; Gwise, T.; Sridhara, R.; Lee, 
E.; Tzou, A.; Philip, R.; Chiu, H.-J.; Ricks, T. K.; Palmby, T.; Russell, A. M.; 
Ladouceur, G.; Pfuma, E.; Li, H.; Zhao, L.; Liu, Q.; Venugopal, R.; Ibrahim, A.; 
Pazdur, R. FDA Approval Summary: Olaparib Monotherapy in Patients with 
Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated with 
Three or More Lines of Chemotherapy. Clin. Cancer Res. Off. J. Am. Assoc. Cancer 
Res. 2015, 21 (19), 4257–4261. https://doi.org/10.1158/1078-0432.CCR-15-0887. 
(11)  Coleman, R. L.; Oza, A. M.; Lorusso, D.; Aghajanian, C.; Oaknin, A.; Dean, A.; 
Colombo, N.; Weberpals, J. I.; Clamp, A.; Scambia, G.; Leary, A.; Holloway, R. 
W.; Gancedo, M. A.; Fong, P. C.; Goh, J. C.; O’Malley, D. M.; Armstrong, D. K.; 
Garcia-Donas, J.; Swisher, E. M.; Floquet, A.; Konecny, G. E.; McNeish, I. A.; 
Scott, C. L.; Cameron, T.; Maloney, L.; Isaacson, J.; Goble, S.; Grace, C.; Harding, 
T. C.; Raponi, M.; Sun, J.; Lin, K. K.; Giordano, H.; Ledermann, J. A.; ARIEL3 
investigators. Rucaparib Maintenance Treatment for Recurrent Ovarian Carcinoma 
after Response to Platinum Therapy (ARIEL3): A Randomised, Double-Blind, 
Placebo-Controlled, Phase 3 Trial. Lancet Lond. Engl. 2017, 390 (10106), 1949–
1961. https://doi.org/10.1016/S0140-6736(17)32440-6. 
(12)  Swisher, E. M.; Lin, K. K.; Oza, A. M.; Scott, C. L.; Giordano, H.; Sun, J.; 
Konecny, G. E.; Coleman, R. L.; Tinker, A. V.; O’Malley, D. M.; Kristeleit, R. S.; 
Ma, L.; Bell-McGuinn, K. M.; Brenton, J. D.; Cragun, J. M.; Oaknin, A.; Ray-
Coquard, I.; Harrell, M. I.; Mann, E.; Kaufmann, S. H.; Floquet, A.; Leary, A.; 
Harding, T. C.; Goble, S.; Maloney, L.; Isaacson, J.; Allen, A. R.; Rolfe, L.; 
Yelensky, R.; Raponi, M.; McNeish, I. A. Rucaparib in Relapsed, Platinum-
Sensitive High-Grade Ovarian Carcinoma (ARIEL2 Part 1): An International, 
Multicentre, Open-Label, Phase 2 Trial. Lancet Oncol. 2017, 18 (1), 75–87. 
https://doi.org/10.1016/S1470-2045(16)30559-9. 
(13)  Talazoparib, Investigators Brochure; 2019. 
(14)  Eisenhauer, E. A.; Therasse, P.; Bogaerts, J.; Schwartz, L. H.; Sargent, D.; Ford, R.; 
Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; Rubinstein, L.; Shankar, L.; 


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Dodd, L.; Kaplan, R.; Lacombe, D.; Verweij, J. New Response Evaluation Criteria 
in Solid Tumours: Revised RECIST Guideline (Version 1.1). Eur. J. Cancer Oxf. 
Engl. 1990 2009, 45 (2), 228–247. https://doi.org/10.1016/j.ejca.2008.10.026. 
(15)  Harris, P. A.; Taylor, R.; Thielke, R.; Payne, J.; Gonzalez, N.; Conde, J. G. 
Research Electronic Data Capture (REDCap)--a Metadata-Driven Methodology and 
Workflow Process for Providing Translational Research Informatics Support. J. 
Biomed. Inform. 2009, 42 (2), 377–381. https://doi.org/10.1016/j.jbi.2008.08.010. 
(16)  Leary, A.; Cowan, R.; Chi, D.; Kehoe, S.; Nankivell, M. Primary Surgery or 
Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues…. 
Am. Soc. Clin. Oncol. Educ. Book Am. Soc. Clin. Oncol. Annu. Meet. 2016, 35, 153–
162. https://doi.org/10.1200/EDBK_160624. 
 
 


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Appendix A. Pill Calendar 
 
Please see attached CRF – Patient Drug Diary 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix B. Informed Consent 
 
Agreement to Participate in a Research Study And Authorization for Use and 
Disclosure of Information 
 
BrUOG 390: Neoadjuvant treatment with Talazoparib for women with newly 
diagnosed, advanced ovarian cancer associated with a mutation in BRCA1 or 
BRCA2 (mBRCA): A Feasibility Trial 
You are being asked to take part in a research study.  All research studies at <INSERT 
HOSPITAL NAME> follow the rules of the state of <INSERT STATE>, the United 
States government and <INSERT HOSPITAL NAME>.  Before you decide whether to 
be in the study, you and the researcher will engage in the “informed consent” process.  
During this process, the researcher will explain the purpose of the study, how it will be 
carried out, and what you will be expected to do if you participate.  The researcher will 
also explain the possible risks and benefits of being in the study, and will provide other 
information.  You should feel free to ask any questions you might have.  The purpose of 
these discussions is for you to decide whether participating in the study is the best 
decision for you. 
 
If you decide to be in the study, you will be asked to sign and date this form in front of 
the person who explained the study to you.  This form summarizes the information you 
discussed.  You will be given a copy of this form to keep.   
 
Nature and Purpose of the Study      
 
Your doctors are participating in this research study with the Principal Investigator, Dr. 
Don S. Dizon in collaboration with Brown University Oncology Research Group 
(BrUOG), which will serve as the central coordinating office for the study.  
 
You are being asked to take part in this study because you have recently been diagnosed 
with advanced ovarian cancer which is associated with a mutation in either BRCA1 or 
BRCA2.  
 
The purpose of this study is to learn whether it is safe to use this oral drug prior to your 
surgery. Talazoparib is a type of drug called a PARP inhibitor.  Prior studies have shown 
PARP inhibitors help keep cancer cells from reproducing, especially in women who have 
BRCA1 and BRCA2 cancers. If you do benefit from treatment, you will be given the 
option to continue it for another two years as maintenance treatment.  
 
This study is financially supported by Pfizer, the maker of Talazoparib. 
 
 
 
How Many People will take part in the Study?  


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We hope to enroll approximately 30 women into this study.  Only women with either 
BRCA1 or BRCA2 mutated advanced ovarian cancer will be eligible to participate in this 
study. 
 
Explanation of Procedures   
 
What will happen if I take part in this research study?  
 
If you take part in this study, you will have exams, tests and procedures to show that you 
can be in the study, and you choose to take part, then you will need the following tests 
and procedures, while on the study.  They are part of regular cancer care.  
 
Screening and prior to participation in this study: 
• Review and sign this informed consent form 
• Confirmation of your diagnosis and BRCA1 or BRCA2 status 
• Your doctor will review your medical history, review your medications, perform a 
physical exam, and see if you have any side effects 
• Vital signs to include height and weight 
• Evaluate how you perform everyday activities – this is called a performance status 
• Obtain blood samples, approximately 6 tablespoons of blood, for the following: 
o A complete blood count (CBC with differential) 
o Blood chemistries (which will test your liver, kidney and electrolyte 
function) 
o A CA-125, which is a tumor marker for ovarian cancer 
o A blood test called an HCG if your ovaries were not removed at the time 
of your surgery.  
• Obtain a CT Scan of the chest, abdomen, and pelvis  
 
During treatment before your surgery/Prior to each cycle of therapy: 
• Your doctor will review your medical history, review your medications, perform a 
physical exam and see if you have any side effects 
• Vital signs to include weight 
• Evaluate how you perform everyday activities – this is called a performance status 
• Obtain blood samples, approximately 6 tablespoons of blood, for the following: 
o A complete blood count (CBC with differential) 
o Blood chemistries (which will test your liver, kidney and electrolyte 
function) 
o A CA-125, which is a tumor marker for ovarian cancer 
o A blood test called an HCG if your ovaries were not removed at the time 
of your surgery  
• Obtain a CT scan of the chest, abdomen, and pelvis at the end of your treatment 
and before your surgery 
• Review the amount and if you took all the study drug, talazoparib 
 
 


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At the time of your surgery: 
• The type of surgery and the report from the analysis of your tissue will be 
obtained 
 
After your surgery: 
• Information on the type and amount of therapy will be obtained 
• Any side effects from the therapy you receive will be obtained 
 
Maintenance Therapy (for patients who continue to receive the study drug talazoparib 
after surgery) 
• Your doctor will review your medical history, review your medications, perform a 
physical exam and see if you have any side effects 
• Vital signs to include weight 
• Evaluate how you perform everyday activities – this is called a performance status 
• Obtain blood samples, approximately 6 tablespoons of blood, for the following: 
o A complete blood count (CBC with differential) 
o Blood chemistries (which will test your liver, kidney and electrolyte 
function) 
o A CA-125, which is a tumor marker for ovarian cancer 
o A blood or urine test called a HCG if you are a women of child-bearing 
potential 
• Obtain a CT scan of the chest, abdomen, and pelvis approximately every three 
months 
• Review the amount and if you took all the study drug, talazoparib 
 
Off study/Follow-up: 
• Your doctor will review your medical history, review your medications, perform a 
physical exam and see if you have any side effects 
• Vital signs to include weight 
• Evaluate how you perform everyday activities – this is called a performance status 
• A blood test, CA-125, which is a tumor marker for ovarian cancer 
• Obtain a CT scan of the chest, abdomen, and pelvis every 3 months for the first 
three years and then every 6 months for years four and five unless you have more 
disease.   
 
Your doctor will speak to you if more or less frequent testing is appropriate. 
 
A CT scan is a radiological test that uses special x-ray equipment to make detailed 
pictures of body tissues and organs. For the CT scan, you may be given a "contrast 
material" (a special dye that makes it easier for doctors to see different tissues in your 
body). The contrast material may be given orally or through one of your veins. Oral 
contrast material is given to you to drink and is used to help outline the stomach and 
intestines. Intravenous (IV) contrast material is given to you by injecting the contrast 
material into a line which is attached to a needle in your arm, and is used to get 
clearer pictures of your body cavity. After you have been given the contrast material 


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(either by mouth, by vein), you will lie flat on a table that will move you into the CT 
scan machine. You will be asked to lie still and may be asked to hold your breath for 
a few seconds. Each CT scan will take about 15 minutes to a half hour. 
 
If you decide to participate in this study, you will receive the study drug Talazoparib 
once a day for three cycles before your surgery unless you have side effects or your 
doctor believes it is best for you to stop.  Each cycle will be 21 days long.   
After your surgery, your doctor may recommend standard of care therapy for your 
cancer.  Once the standard of care therapy is complete, you may be eligible to take 
the study drug Talazoparib for up to an additional 24 months. 
 
How long will I be in the study? 
 
You will continue to be in the study until you finish protocol therapy or experience 
disease progression, discontinue treatment due to side effects, your doctor believes it is in 
your best interest or you withdraw informed consent. 
 
Follow up for this study is expected to be for a total of five years. 
 
Can I stop being in the study?  
 
Yes. You can decide to stop at any time.  Tell the study doctor if you are thinking about 
stopping or decide to stop.  He or she will tell you how to stop safely.   
It is important to tell the study doctor if you are thinking about stopping so any risks from 
the discontinuation of treatment can be evaluated by your doctor.  Another reason to tell 
your doctor that you are thinking about stopping is to discuss what follow-up care and 
testing could be most helpful for you.  
The study doctor may stop you from taking part in this study at any time if he/she 
believes it is in your best interest; if you do not follow the study rules; or if the study is 
stopped.  
 
Costs for participating in this study  
 
Pfizer, the maker of the study drug Talazoparib, is providing the drug at no cost.   
 
The study procedures done during this research study are considered "routine clinical 
services" that you would have received even if you were not in the research study. 
Examples are blood tests, doctor visits, diagnostic imaging tests such as CT scans. These 
services will be billed to your health insurance company, but you will be responsible for 
paying any deductibles, co-payments, or co-insurance that are a normal part of your 


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health insurance plan.  If you do not have health insurance, you will be responsible for 
those costs.  
 
For more information on clinical trials and insurance coverage, you can visit the 
National Cancer Institute's Web site at 
http://cancer.gov/clinicaltrials/understanding/insurance-coverage. You can print a copy 
of the "Clinical Trials and Insurance Coverage" information from this Web site. 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and 
ask them to send you a free copy. 
 
 
Will I be paid for taking part in this study? 
 
You will not be paid for taking part in this study. 
 
Contact Information: If you have any questions regarding this study, you may contact 
your site 
Principal Investigator, <INSERT CONTACT NAME> at <INSERT PHONE 
NUMBER>. 
 
Discomforts and Risks 
You may have side effects while on this study.  We will monitor everyone in the study 
for any side effects. Contact your study doctor if you experience a side effect or have any 
questions about possible side effects. 
 
Side effects may be mild or serious.  We may give you medicines to help lessen side 
effects.  Some side effects will go away as soon as you stop taking the drug.  In some 
cases, side effects can be serious, long-lasting, or can cause death.  In some cases, side 
effects can be serious, long-lasting, or may never go away.  
 
Taking part in this study may lead to time away from work. 
 
Risks related to Talazoparib: 
 
You may have side effects while you are in the study, but you will be carefully checked 
by the study doctor for any problems. There may be risks or side effects of the study drug 
that are unknown at this time. You should tell the study doctor/staff about anything that is 
bothering you or any side effects you have, even if you do not think they are related to 
the study drug.  
 
The following is a list of the most medically significant or most common side effects 
reported in completed studies considered to be related to Talazoparib. In some cases, 
side effects can be serious, long-lasting, or can cause death.  Some side effects go away 
soon after you stop the study drug/therapy and some may never go away.  The study 
doctor may alter the dosage regimen of Talazoparib (if allowed by the study) or give you 


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medicines to help lessen the side effects.  This is not a complete list of all side effects 
that may occur.  For more information about risks and side effects, please ask the study 
doctor. 
 
Very Common (occurs in 1 in 10 subjects or more (10% or more chance that this will 
happen): 
• Fatigue (feeling tired) 
• Nausea, vomiting and diarrhea 
• Anemia (decreased hemoglobin, which is a protein in red blood cells that carries 
oxygen through the body). This can lead to feeling tired and pale skin 
• Leukopenia (decreased number of a type of white blood cell count, leukocytes, 
which can make you at increased risk for infection) 
• Neutropenia (decreased number of white blood cells called neutrophils, which can 
make you at increased risk for infection) 
• Thrombocytopenia (decreased number of a component of blood called platelets 
that help with the formation of blood clots) 
• Lymphopenia (decreased number of a type of blood cells called lymphocytes, 
which have important functions in the immune system) 
 
Common (between a 1% to less than 10% chance that this will happen): 
 
• Hair loss (alopecia) 
• Abdominal pain 
• Headache 
• Decreased appetite 
• Dizziness 
• Dysgeusia (altered taste) 
• Dyspepsia (heartburn) 
• Stomatitis (sores inside of your mouth) 
• Sinusitis (sinus infection) 
• Dry skin 
• Mucosal inflammation (inflammation of the lining of the stomach) 
• Aspartate aminotransferase increased (elevation in your blood that can show signs 
of liver damage) 
 


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Uncommon (between a 0.1 to less than 1% chance that this will happen): 
 
• Death 
 
Risk of Secondary Cancers:  
 
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) 
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been 
reported in a very small number of patients treated with Talazoparib. MDS is a pre-
cancerous condition where the bone marrow is not as good at producing blood cells (red 
and/or white blood cells and/or platelets) as it was before. People with MDS need 
transfusions (red blood cells and/or platelets) and/or other treatments. In some cases, 
MDS will progress to AML, which is a cancer of the bone marrow where more 
abnormal and immature white blood cells (also called blasts) are made than normal 
white blood cells. People with AML need treatment with chemotherapy and/or a 
transplant. Patients may develop AML without first being diagnosed with MDS. 
Cases of MDS and AML have also been reported with PARP inhibitors similar to 
rucaparib. At this time, it is not known whether rucaparib or other PARP inhibitors 
cause MDS or AML, or if these developed as a result of previous chemotherapy these 
patients received. Your study doctor will closely monitor your blood cell levels during 
treatment. If your study doctor has any concerns about your blood counts you may be 
asked to have a biopsy of your bone marrow.  
 
Reproductive Risks 
 
Because the drugs in this study can affect an unborn baby, you should not become 
pregnant while on this study. Ask your study doctor for more information regarding 
preventing pregnancy during the study treatments. If you have a newborn, you should not 
nurse your baby while on this study. If you are premenopausal, your periods are likely to 
stop temporarily and may stop permanently due to the study treatments, which may lead 
to symptoms of menopause, such as hot flashes, and the inability to become pregnant, 
which may be permanent. If you are concerned about this, ask your study doctor about 
options for preserving your reproductive choices, which may include referral to a 
specialist in this field.   
By signing this document, you are acknowledging that you understand and agree to the 
information presented in this Reproductive Risk section. 
 
Antiemetics (anti-nausea medications): Various medications used to prevent nausea 
and vomiting may cause drowsiness, dry mouth, diarrhea, constipation, headache, 
restlessness, agitation, anxiety, dizziness, involuntary tremors, skin rash, and possible 
allergic reaction. Your doctor may prescribe such medications for you prior to starting, or 
else, it will be made available to you if you have symptoms.  
 


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There may be other side effects that have not been reported. If you have any unusual 
symptoms, you should report them immediately to your doctor or nurse. 
 
 
Benefits 
 
Taking part in this study may or may not make your health better. Your condition may 
even get worse during the study. We do know that the information from this study will 
help doctors learn more about the study drug Talazoparib with your type of cancer.  This 
information could help future cancer patients. However, there is no guarantee that this will 
happen. 
 
Alternative Therapies 
 
What other choices do I have if I do not take part in this study?  
 
Talk to your doctor about your choices before you decide if you will take part in this study. 
 
Refusal/Withdrawal 
 
It is up to you whether you want to be in the study.  You are not required to enroll or 
participate.  If you decide to participate, you can always change your mind and quit at 
any time.  If you decide not to be in the study, or if you quit later, you will still be able to 
get the standard of care health care services you normally get.  If you join, but later on the 
researcher or your doctor feels being in the study is no longer good for you, they may 
choose to take you out of the study before it is over.  If new information becomes 
available that might change your mind about whether you want to stay in the study the 
researcher will share this information with you as soon as possible. 
 
It is important to tell the study doctor if you are thinking about stopping so any risks from 
the discontinuation of treatment can be evaluated by your doctor.  Another reason to tell 
your doctor that you are thinking about stopping is to discuss what follow-up care and 
testing could be most helpful for you.  
 
If you make the decision to withdraw from this study (stop taking study medication) for 
any reason, tell your doctor immediately. You will be asked to sign a form indicating 
whether you give your permission for your doctor and the research staff to continue to 
collect and submit follow-up information on your health status from your physicians and 
medical record. After signing the form, you still have the right to change your mind, at 
any time, regarding follow-up after withdrawal. 
 
Medical Treatment/Payment in Case of Injury 
A research injury is any physical or mental injury or illness caused by being in the study. 
If you are injured by a medical treatment or procedure you would have received even if 


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59 
 
you were not in the study that is not a research injury. To help avoid research injury and 
added medical expenses, it is very important to follow all study directions carefully. If 
you do experience a research injury, <INSERT HOSPITAL NAME> or the study doctor 
can arrange medical treatment for you. Such treatment will be paid for as described 
below.  
 
Medical treatment will be available if you suffer a research related injury; however, you 
and/or your health insurance company will be charged for this treatment. The study will 
not pay for this medical treatment. Neither Dr. Don Dizon nor the sponsor of the study, 
BrUOG, the coordinating center, have money set aside to reimburse you for medical bills 
from treatment of a research related injury or otherwise compensate you in the event of a 
study-related injury.  
 
If you have insurance and have a research injury that is not covered by the study, it is 
possible that some or all of the cost of treating you could be billed to your insurer. If your 
health insurance will not cover such costs, it is possible you would have to pay out of 
pocket. In some cases, <INSERT HOSPITAL NAME> might be able to help you pay if 
you qualify for free care under <INSERT HOSPITAL NAME> policy. However, 
<INSERT HOSPITAL NAME> has no policy to cover payment for such things as lost 
wages, expenses other than medical care, or pain and suffering. 
 
Rights and Complaints 
Signing this form does not take away any of your lawful rights. If you have any 
complaints about this study, or would like more facts about the rules for research studies, 
or the rights of people who take part in research studies you may contact <ENTER 
CONTACT INFORMATION IRB>, in the <ENTER NAME OF IRB>, at <ENTER 
CONTACT INFORMATION>.  
 
Confidentiality 
Your research records will be treated as private health care records and will be protected 
according to <INSERT HOSPITAL NAME> privacy practices and policies that are based 
on state and federal law. In particular, federal law requires us to get your permission to 
use or disclose (release your information to someone outside of<INSERT HOSPITAL 
NAME>) your health information for research purposes. If you sign this form you agree 
to be in this research study and you permit the use and disclosure of your health 
information for the purpose of conducting the research, providing treatment, collecting 
payment and running the business of the hospital. This permission has no expiration date. 
You may withdraw from the study at any time. However, if you do not want the 
researchers to use or disclose any further information in this study you must cancel 
permission in writing and may do so at any time. If you cancel your permission, you will 
stop taking part in the study and no new information will be collected about you. 
However, if you cancel your permission, it will not apply to actions already taken or 
information already collected about you by the hospital or the researchers before you 
canceled your permission.  
 


 Br U O G 3 9 0: Versi o n Date: 3/ 2 2/ 2 0 2 0, 4/ 6/ 2 0 2 0, 7/ 2 2/ 2 0 2 0, 8/ 1 1/ 2 0 2 0, 1 0/ 3 0/ 2 0, p ost F D A: 1 1/ 1 3/ 2 0, 
1 1/ 2 3/ 2 0; 1/ 7/ 2 1, A # 1 6/ 9/ 2 1  
6 0 
 
Ge ner all y, t he e ntire r esearc h r ec or d a n d a n y me di cal rec or ds hel d b y t he h os pital ma y be 
use d a n d rel ease d f or r es earc h p ur p oses. T h e f oll o wi n g pe o pl e or b usi nesses/c o m pa nies 
mi g ht use, rel ease, or recei ve s uc h i nf or mati o n:  
 
 T he researc h er a n d t h eir s u p p ort staff;  
 T he st u d y s p o ns or, PI, D o n Diz o n, M D, Br U O G, T he Br o w n U ni versit y O nc ol o g y 
Researc h Gr o u p a n d t h eir re pr ese ntati ves a n d Pfiz er, ( Fi na ncial st u d y s u p p orter);  
 D oct ors, n urses, la b or at ories a n d ot hers w h o pr o vi de ser vices t o y o u i n c o n necti o n 
wit h t his st u d y;  
 T he C o m pa n y or s ecti o n of t he U. S. g o v er n me nt t hat is pa yi n g f or t he st u d y a n d ot h ers 
t he y hir e t o o versee, a d mi nister, or c o n d uct t he res earc h;  
 T he U nite d States F o o d a n d Dr u g A d mi nistrati o n, t he De part me nt of Healt h a n d 
H u ma n Ser vices, t he Offi ce of I ns p ect or G e neral, a n d t he Offi ce of Ci vil Ri g hts;  
 Pe o ple w h o v ol u nteer t o be patie nt a d v ocates or researc h v ol u nteer pr otect ors;  
 Me m bers of t he h os pital's a d mi nistrati ve staff res p o nsi ble f or re vie wi n g, a p pr o vi n g 
a n d a d mi nisteri n g cli nical trials a n d ot her healt hcare or researc h acti vities.  
 
T here are ti mes w h e n t he la w mi g ht re q uire or p er mit <I N S E R T H O S PI T A L N A M E > t o 
releas e y o ur healt h i nf or mati o n wit h o ut y o ur per missi o n. F or e x a m ple, < E N T E R 
S T A T E > la w r e q uires r esearc h ers a n d h ealt h care w or kers t o re p ort a b use or ne glect of 
c hil dre n t o t he De p art me nt of C hil dre n, Y o ut h a n d Fa milies ( D C Y F) a n d t o re p ort a b use 
or ne glect of p e o ple a ge 6 0 a n d ol der t o t he De p art me nt of El derl y Affairs. 
 
All resear c hers a n d healt h care pr o vi ders are re q uire d t o pr ote ct t he pri vac y of y o ur 
healt h car e i nf or mati o n. Ot her pe o ple a n d b usi nesses/ or ga nizati o ns t hat are n ot healt h 
care pr o vi ders are n ot r e q uire d b y l a w t o d o t hat s o it is p ossi ble t he y mi g ht re- releas e 
y o ur i nf or mati o n.  
 
Y o u ha ve t he ri g ht t o r ef use t o si g n t his f or m a n d n ot partici pate i n t he res earc h. Y o ur 
ref usal w o ul d h a ve n o eff ect o n y o ur treat me nt, c h ar ges bille d t o y o u, or be nefits at a n y 
<I N S E R T H O S PI T A L N A M E >  healt h care site. If y o u d o n ot si g n, y o u will n ot be a ble 
t o e nr oll i n t he researc h st u d y a n d will n ot recei ve treat me nt as a st u d y partici pa nt.  
 
If y o u deci d e t o q uit t he st u d y aft er si g ni n g t his f or m (as descri b e d i n Secti o n 6) n o ne w 
i nf or mati o n will be c ollecte d a b o ut y o u u nless y o u ga v e us per missi o n t o d o s o. 
H o we ver, t he h os pital or t h e researc h ers ma y c o nti n ue t o use i nf or mati o n t hat was 
c ollecte d bef ore y o u q uit t he st u d y t o c o m plete a nal ysis a n d re p orts of t his researc h. 
 
Y o u will n ot be all o we d t o see or c o p y t h e i nf or mati o n descri be d i n t his f or m as l o n g as 
t he researc h st u d y is o pe n.  Y o u ma y s ee a n d c o p y t he i nf or mati o n w he n t he st u d y is 
c o m plete d.  
 
A d diti o nall y, a des cri pti o n of t his cli nical trial will be a vaila ble o n 
htt p:// w w w. Cli nic al Tri als. g ov, as re q uire d b y U. S. la w. T his We b site will n ot i ncl u de 


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61 
 
information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time.  
 
 
For more detail about your privacy rights see the <INSERT HOSPITAL NAME>Joint 
Privacy Notice which has or will be given to you. 
 
SIGNATURE 
 
I have read this informed consent and authorization form.  ALL OF MY QUESTIONS 
HAVE BEEN ANSWERED, AND I WANT TO TAKE PART IN THIS RESEARCH 
STUDY. 
 
By signing below, I give my permission to participate in this research study and for the 
described uses and releases of information.  I also confirm that I have been now or 
previously given a copy of the <INSERT HOSPITAL NAME> Privacy Notice 
 
 
 
 
 
The Researcher is required to provide a copy of this consent to you.  
 
_________________________________________ 
________          ____________ 
Signature of study volunteer/authorized representative* 
Date         and    Time when 
signed 
  
 
I was present during the consent PROCESS AND signing of this agreement by the study 
volunteer or authorized representative 
 
__________________________________________ 
 
______________ 
Signature of witness (required if consent  
 
 
 
Date 
is presented orally or at the request of the IRB) 
 
 
 
 
 
 
 
 
 
__________________________________________ 
 
______________ 
Signature of Translator 
 
 
 
 
 
Date 
 
___________________________________________ 
________          __________ 
Signature of researcher or designate  
 
Date    
Time when signed 
 
* If signed by agent other than study volunteer, please explain below. 
________________________________________________________________________ 
________________________________________________________________________ 
 
 
This informed consent document expires on _________________.   
DO NOT sign this document after this expiration date 


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Appendix C BrUOG checklist for patient registration  
 
BrUOG 390: Neoadjuvant treatment with Talazoparib for women with newly 
diagnosed, advanced ovarian cancer associated with a mutation in BRCA1 or 
BRCA2 (mBRCA): A Feasibility Trial 
 
Patient initials: __________ 
Hospital where pt will receive treatment: __________ 
Day 1 of treatment: _________ 
Treating MD:__________ 
Your name:__________ 
☐ Site: please include this table in a note or email and have treating MD confirm. Please 
submit this checklist via email or upload into REDCap. 
 
Inclusion criteria  
☒indicates patient meets inclusion 
Site- 
comment/source 
to verify 
BrUOG 
verified 
(Y/N)*internal 
use 
☐ 4.1.1Volunteers must have clinical and 
radiographic evidence of newly detected FIGO 
stage II, III or IV epithelial ovarian, primary 
peritoneal or fallopian tube cancer, deemed by a 
gynecologic oncologist as not amenable to an R0 
resection at presentation.  
 
 
☐ 4.1.2 Institutional confirmation of Müllerian 
epithelial adenocarcinoma.  
 
 
☐ 4.1.3 Histologic epithelial cell types: high grade 
serous carcinoma, high grade endometrioid 
carcinoma, or a combination of these. 
 
 
☐ 4.1.4 Documented mutation in BRCA1 or 
BRCA2 by genetic or commercial somatic testing. 
Reports will require submission at the time of 
enrollment.  
 
 
☐ 4.1.5 Measurable disease as defined by RECIST 
1.1. Measurable disease is defined as at least one 
lesion that can be accurately measured in at least 
one dimension (longest diameter to be recorded). 
Each lesion must be ≥ 10 mm when measured by 
CT, MRI or caliper measurement by clinical exam; 
or ≥ 20 mm when measured by chest x-ray. Lymph 
nodes must be ≥ 15 mm in short axis when 
measured by CT or MRI. 
 
 


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☐ 4.1.6 Age ≥ 18 
 
 
☐ 4.1.7 Adequate hematologic function determined 
within 28 days of consent as follows:  
• ☐ ANC greater than or equal to 1,500/mcl. 
NOTE: ANC cannot have been induced by 
granulocyte colony stimulating factors.  
• ☐ Platelets greater than or equal to 
100,000/mcl  
• ☐ Hemoglobin greater than 10 mg/dl 
(NOTE: While transfusions are permitted to 
achieve baseline hemoglobin level, patients 
must not have transfusion within 14 days 
prior to obtaining baseline screening labs)  
• ☐ Creatinine clearance > 15ml/min. (NOTE: 
Please see Section 6.2.1 for dosing 
requirements for patients with renal 
insufficiency)  
 
 
☐ 4.1.8 CrCl = (140- age in years) x weight in kg x 
0.85/ 72 x serum creatinine in mg/dL 
 
 
☐ 4.1.9 Adequate hepatic function within 14 days 
prior to registration defined as follows:  
• ☐ Bilirubin ≤ 1.5 x ULN  
• ☐ ALT and AST ≤ 2.5 x ULN  
• ☐ Alkaline phosphatase ≤ 2.5 x ULN 
 
 
 
☐ 4.1.10 Neurologic function: Neuropathy (sensory 
and motor) less than or equal to CTCAE v.5.0 
Grade 1. 
 
 
 
☐ 4.1.11 Ability to swallow and retain oral 
medication. Adequate gastrointestinal absorption 
with no use of parenteral nutrition within two weeks 
of trial enrollment and no evidence of bowel 
obstruction. 
 
 
☐ 4.1.12 The volunteer must provide study-specific 
informed consent prior to study entry. 
 
 
 
Ineligibility criteria- ☒indicates patient does not meet criteria 
☐ 4.2.1Suspected non-gynecologic malignancy, 
evidence by tumor markers and/or histologic 
evaluation.  
 
 


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☐ 4.2.2 Prior history of other invasive 
malignancies, with the exception of nonmelanoma 
skin cancer and other specific malignancies as noted 
in Section 4.2.4 and Section 4.2.5 are excluded if 
there is any evidence of other malignancy being 
present within the last three years (2 years for breast 
cancer, see Section 4.2.4). Volunteers are also 
excluded if their previous cancer treatment 
contraindicates this protocol therapy.    
 
 
☐ 4.2.3 Prior chemotherapy for any abdominal or 
pelvic tumor within the last three years are 
excluded. Volunteers may have received prior 
adjuvant chemotherapy and radiotherapy for 
localized breast cancer, provided that it was 
completed more than 2 years prior to registration, 
the volunteer remains free of recurrent or metastatic 
disease and hormonal therapy has been 
discontinued.  
 
 
☐ 4.2.4 Prior radiotherapy to any portion of the 
abdominal cavity or pelvis or thoracic cavity within 
the last three years are excluded. Prior radiation for 
localized cancer of the head and neck or skin is 
permitted, provided that it was completed more than 
three years prior to registration, and the volunteer 
remains free of recurrent or metastatic disease. 
 
 
☐ 4.2.5 Synchronous primary endometrial cancer, 
or a past history of primary endometrial cancer, 
unless all of the following conditions are met: Stage 
not greater than I-A, grade 1 or 2, no more than 
superficial myometrial invasion, without vascular or 
lymphatic invasion; no poorly differentiated 
subtypes, including serous, clear cell or other FIGO 
grade 3 lesions. 
 
 
☐ 4.2.6 Severe, active co-morbidity defined as 
follows:  
• ☐ Chronic or current active infectious 
disease requiring systemic antibiotics, 
antifungal or antiviral treatment  
• ☐ Known brain or central nervous system 
metastases or history of uncontrolled 
seizures  
• ☐ Clinically significant cardiac disease 
including unstable angina, acute myocardial 
infarction within 6 months from enrollment, 
 
 


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New York Heart Association Class III or IV 
congestive heart failure, and serious 
arrhythmia requiring medication (this does 
not include asymptomatic atrial fibrillation 
with controlled ventricular rate).  
• ☐ Partial or complete gastrointestinal 
obstruction  
☐ 4.2.7 Volunteers who are not candidates for 
major abdominal surgery due to known medical 
comorbidities. 
 
 
☐ 4.2.8 Volunteers with any condition that in the 
judgment of the investigator would jeopardize 
safety or volunteer compliance with the protocol.  
 
 
☐ 4.2.9 Concurrent anticancer therapy (e.g. 
chemotherapy, radiation therapy, biologic therapy, 
immunotherapy, hormonal therapy, investigational 
therapy). 
 
 
☐ 4.2.10 Receipt of an investigational study drug 
for any indication within 30 days or 5 half-lives 
(whichever is longer) prior to Day 1 of protocol 
therapy. 
 
 
☐ 4.2.11 Prior exposure to a PARP inhibitor 
 
 
☐ 4.2.12 People of child-bearing potential are 
excluded. Criteria are as follows: 
• ☐ Any volunteer who has experienced 
menarche and who has not undergone 
surgical sterilization (hysterectomy and/or 
bilateral oophorectomy) or who is not 
postmenopausal. Menopause is defined 
clinically as 12-month amenorrhea in a 
woman over 45 in the absence of other 
biological or physiological causes.  
• ☐ Volunteers who are pregnant or nursing. 
Volunteers must agree to use adequate 
contraception (hormonal or barrier method 
of birth control; abstinence) prior to study 
entry, for the duration of study participation, 
and for at least 7 months after completing 
therapy.  
• ☐ People with an intact uterus and ovaries 
must have must have a screening negative 
serum or urine pregnancy test within 14 days 
of registration. A second pregnancy test 
 
 


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must be done within 24 hours prior to the 
start of the first cycle of study treatment. 
☐ 4.2.13 Potent P-gp inhibitors that result in ≥ 2-
fold increase in the exposure of an in vivo probe P-
gp substrate, including: amiodarone, carvedilol, 
clarithromycin, cobicistat, dronedarone, 
erythromycin, glecaprevir/pibrentasvir, indinavir, 
itraconazole, ketoconazole, lapatinib, lopinavir, 
propafenone, quinidine, ranolazine, ritonavir, 
saquinavir, sofosbuvir/velpatasvir/voxilaprevir, 
telaprevir, tipranavir, valspodar and verapamil. 
More instruction available at:  
https://www.druginteractionsolutions.org/. 
 
 
 
The pre-treatment assessment support documentation, per the requirements under the 
study parameters section of this study, as well as the consent form must be uploaded into 
REDCap the time of registration.   
Pre-Treatment 
assessments 
The day an assessment 
(PE, Lab, scan etc.) is 
performed is considered 
day 0 for counting. 
Date 
completed 
Required for 
Registration 
Upload to 
REDCap (site 
to indicate Y/N) 
BrUOG verified  
(Y/N)*internal use 
Informed consent 
 
☐ ≤28 days 
 
 
Tissue confirmation 
 
☐ X 
 
 
mBRCA confirmation  
 
☐ X 
 
 
Concurrent meds  
 
☐ ≤28 days 
 
 
History and Physical exam  
 
☐ ≤28 days 
 
 
Blood pressure, Pulse  
 
☐ ≤28 days 
 
 
Weight and Height (Height 
only at baseline) 
 
☐ ≤28 days 
 
 
Performance status 
 
☐ ≤28 days 
 
 
CBC w/diff 
 
☐ ≤28 days 
 
 
Serum chemistry* 
 
☐ ≤28 days 
 
 
CA125 
 
☐ ≤28 days 
 
 
HCG**  
 
☐ ≤14 days 
 
 
Adverse event evaluation 
 
☐ ≤14 days 
 
 


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CT Chest, Abdomen, and 
Pelvis 
 
☐ ≤28 days 
 
 
*Electrolytes including BUN, Crea, Ca, and Mg; LFTs including Bilirubin, ALT, AST, Alk Phos, and albumin.  
** Urine or serum in applicable volunteers, per eligibility criteria.  
 
 
 
BrUOG use: 
CRC completing checklist     
 
 
 
Second reviewer: 
Initials: 
 
 
 
 
 
 
Initials: 
Date:  
 
 
 
 
 
 
Date: 


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Appendix D. FDA MedWatch Reporting Checklist for site to submit with report 
 
Patient #: ______ Initials: _____ 
☐ Initial SAE Report   ☐ Follow-up #1 SAE Report    ☐ Follow-up #2 SAE Report 
☐ Report must be typed 
 
☐ Section A Include protocol # (and patient number, if assigned) (i.e. Br390 initials #) 
 
Section B Description of event:  
☐ Include description of event (i.e. this is an initial SAE report to document pt X 
presented to the hospital on XX-XX-XXXX for X, X, X) 
 
☐ Include protocol description (i.e. pt X began treatment on BrUOG 390 on X) 
 
☐ Include treatment regimen (dosing frequency, combination therapy) (i.e. patient 
received last dose of X on XX-XX-XX) 
 
☐ Clearly outline which events are being reported as serious and non-serious (i.e. serious 
events are grade 3 fatigue and grade 3 nausea, non-serious events at time of 
hospitalization include grade 1 fever and grade 1 vomiting) 
 
☐ Investigator’s assessment of the relationship of the serious adverse event to talazoparib 
and suspect medication (i.e. fatigue is not related to talazoparib, related to disease) 
 
☐ Include treatment of event (i.e. patient received IV antibiotics and fluids for treatment 
of serious event X) 
 
☐ Outcome of event, if known (i.e. grade 3 serious fatigue resolved upon discharge or 
grade 3 serious fatigue downgraded to non-serious grade 2 upon discharge) 
 
☐ Action taken with talazoparib as a result of the SAE and expectedness (based on the IB 
and consent) if it is unknown at the time of submission, please indicate “at this time, 
treating MD is uncertain when treatment with talazoparib will resume” 
 
☐ Create unscheduled event in REDCap and upload all supportive documents 
 
☐ A final report to document discharge from hospital (or resolution of important medical 
event) if patient still admitted at the time of report, this must be submitted as a follow-up 
 
☐ Section C Suspect Products(s) site to complete if the initial reporter suspected the 
product was associated with the SAE. If the product was not suspected to be associated 
with the SAE, only C2 conmed section should be completed (lot # and expiration date 
must be included if applicable). 


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