A Phase II, Randomized, Double-Blind Study of the Use of Rucaparib vs. Placebo Maintenance Therapy in Metastatic and Recurrent Endometrial Cancer
Phase: PHASE2
Conditions: Metastatic Endometrial Cancer
Sponsor: University of Colorado, Denver

 
 
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A Phase II, randomized, double-blind, study of the use 
of Rucaparib vs. placebo maintenance therapy in 
metastatic and recurrent endometrial cancer 
 
Protocol Number: 
 
 
338-IIT-088/COMIRB # 
Principal Investigator: 
 
 
Bradley Robert Corr, MD 
Saketh Ram Guntupalli, MD 
Coordinating Center 
and Lead Principal 
Investigator:  
University of Colorado Denver 
Bradley Robert Corr, MD  
Funded by:  
Clovis Oncology 
Version Date:   
09 JUN 2021 
 

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STATEMENT OF COMPLIANCE 
 
This is an investigator-initiated study.  The principal investigator (PI), Bradley Robert Corr, is 
conducting the study and acting as the sponsor.  As the sponsor-investigator, both the legal/ethical 
obligations of a PI and those of a sponsor will be followed. 
 
The trial will be carried out in accordance with Good Clinical Practice (GCP) as required by 
applicable United States (US) laws and applications, including but not limited to United States 
(US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR 
Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
 
The PI will assure that no changes to the protocol will take place without documented approval 
from the Institutional Review Board (IRB). All personnel involved in the conduct of this study 
have completed Human Subjects Protection Training.  
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments.  
 
 
 
Sponsor-Lead Principal Investigator:   
 
 
 
 
 
 
  
 
 
 
 
 
 
                        Print/Type Name  
 
 
Signed:   
 
 
 
 
 
 
 
 
 
Date:    
 
  
 
 
Site Principal Investigator:   
      
 
 
 
 
 
 
  
 
 
 
 
 
 
                        Print/Type Name  
 
 
Signed:   
 
 
 
 
 
 
 
 
 
Date:    
 
  
 
 
Site Principal Investigator:   
      
 
 
 
 
 
 
  
 
 
 
 
 
 
                        Print/Type Name  
 
 
Signed:   
 
 
 
 
 
 
 
 
 
Date:    
 
  
 
 
 

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LIST OF ABBREVIATIONS 
 
ACRONYM 
DESCRIPTION 
ADP  
Adenosine Diphosphate 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AIDS 
Acquired Immunodeficiency Syndrome 
AKT 
Protein Kinase B 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
AML 
Acute Myeloid Leukemia 
ANC 
Absolute Neutrophil Count 
AP 
Cisplatin + Adriamycin  
AST 
Aspartate Transaminase 
BID 
Twice a day 
BRCA 
Breast Cancer 
BUN 
Blood Urea Nitrogen 
C1D1 
Cycle 1 Day 1 
CBC 
Complete blood Count 
CFR 
Code of Federal Regulations 
CMP 
Comprehensive Metabolic Panel 
CNS 
Central Nervous System 
CO 
Colorado 
CO2 
Carbon Dioxide 
COIC 
Office of Regulatory Compliance Conflicts of Interest and Commitment Management 
Cr 
Creatinine 
CR 
Complete Response 
CT 
Computerized Tomography 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP2C19 
Cytochrome P450 2C19 
CYP2C9 
Cytochrome P450 2C9 
CYP3A 
Cytochrome P450, family 3, subfamily A 
DCC 
Data Coordinating Center 
dL 
Deciliter 
DNA 
Deoxyribonucleic acid 
DSM 
Data Safety Monitoring 
DSMB 
Data Safety Monitoring Board 
DSMC 
Data Safety Monitoring Committee 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
FIGO 
 International Federation of Gynecology and Obstetrics 
FSH 
Follicle Stimulating Hormone 
g 
Gram 
GCP 
Good Clinical Practice 

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GCSF 
Granulocyte-Colony Stimulating Factor 
GFR 
Glomerular Filtration Rate 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GOG 
Gynecologic Oncology Group 
HDL 
High Density Lipoprotein 
HDPE 
High Density Polyethylene 
HIV 
Human Immunodeficiency Virus 
HPMC 
Hydroxypropyl Methylcellulose 
HR 
Homologous Recombination 
HRD 
Homologous Recombination Deficiency 
ICF 
Informed Consent Form 
ICMJE 
International Committee of Medical Journal Editors 
IDS 
Investigational Drug Service 
IIT 
Investigator-Initiated Trial 
IEC 
Institutional Ethics Committee 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IT 
Information Technology 
LDL 
Low Density Lipoprotein 
mCRPC 
Metastatic Castration-Resistant Prostate Cancer 
MCH 
Mean Corpuscular Hemoglobin  
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MDS 
Myelodysplastic Syndrome 
mg 
Milligram 
mL 
Milliliter 
MMR 
Mismatch Repair 
MSI 
Microsatellite Instability 
mTOR 
Mechanistic Target of Rapamycin 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NIH IC 
National Institute of Health Institute and Centers 
NRG 
National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation 
Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG 
NSAE 
Non-Serious Adverse Event 
OHRP 
Office of Human Research Protection 
ORR 
Overall Response Rate 
OS 
Overall Survival  
PA 
Pennsylvania 
PARP 
Polymerase 
PD 
Progressive Disease 
PD1 
Programmed Death 1 
PIS 
Patient Information Sheet 
PFS 
Progression free survival 
PI 
Principal Investigator 
PIK3CA 
Phosphatidylinositol 3-kinase 
PO 
by mouth 

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PR 
Partial Response 
PTEN 
Phosphatase and Tensin homolog 
QD 
once a day 
QC 
Quality Control 
RBC 
Red Blood Cells 
RCT 
Randomized Controlled Trial  
REDCap 
Research Electronic Data Capture 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SD 
Stable Disease 
SOC 
Standard of Care 
SOP 
Standard Operating Procedure 
TAP 
Cisplatin + Adriamycin + Paclitaxel 
TIA 
Transient Ischemic Attack 
UAE 
Unanticipated Event 
UAP 
Unanticipated Problem 
UCCC 
University of Colorado Cancer Center 
UCD 
University of Colorado Denver 
µL 
Microliter 
ULN 
Upper Limit of Normal 
US 
United States 
VLDL 
Very low-density lipoprotein 
WBC 
White Blood Cells 
 
 

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PROTOCOL SUMMARY / SYNOPSIS 
Protocol Title: 
A Phase II, randomized, double-blind, study of the use of Rucaparib 
vs. placebo maintenance therapy in metastatic and recurrent 
endometrial cancer 
 
Objectives: 
 
• Primary Objective: 
1. To measure progression free survival (PFS) with the use of 
Rucaparib compared to placebo in women with recurrent or 
metastatic endometrial cancer after first line chemotherapy. 
 
• Secondary Objectives:  
1. To measure overall survival (OS) with the use of Rucaparib 
compared to placebo in women with recurrent or metastatic 
endometrial cancer after first line chemotherapy. 
2. To determine the efficacy with the use of Rucaparib compared 
to placebo in women with recurrent or metastatic endometrial 
cancer after first line chemotherapy as measured by overall 
response rate (ORR) in patients with measurable disease. 
3. Safety and tolerability. Safety endpoints including incidence 
and severity of adverse events and significant laboratory 
abnormalities.  
 
• Tertiary/Exploratory: 
1. To preliminarily assess the efficacy with the use of Rucaparib 
compared to placebo in women with recurrent or metastatic 
endometrial cancer after first line chemotherapy in relation to  
HRD, BRCA, PTEN, PIK3CA and AKT. 
 
 
Endpoint: 
• Primary Endpoint: 
Progression free survival (PFS)  
 
• Secondary Endpoints: 
Overall Survival (OS)  
Overall Response rate (ORR) 
Toxicity 
 
• Tertiary/exploratory: 
Disease response for molecular measures (BRCA, HRD, PTEN, 
PIK3CA, AKT) 
 
Population: 
• Sample size 
o Maximum number of participants that can be enrolled is 
138  
o Minimum number of participants to be enrolled 123  

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• Gender Female 
• Age Range 18-89   
• Demographic group Patients with a primary Stage III/IV or 
recurrent endometrial cancer whom have received at least one 
prior chemotherapy regimen and no more than two prior cytotoxic 
regimens (including hormonal therapy) 
• General health status ECOG performance status of 0, 1 or 2 
• Geographic location Denver, CO and Philadelphia, PA; USA 
 
Phase: 
II 
Number of 
Participating Sites 
enrolling 
participants: 
Total 4 sites 
Description of Study 
Agent: 
Rucaparib (Rubraca®) 
Study Duration: 
24 months post treatment follow-up for an estimated total study 
duration of 48 months 
 
 
SCHEMATIC OF STUDY DESIGN 
 
1 
PARTICIPATING SITES 
A complete and current listing of investigators, research personnel, research facilities and other 
study centers (if applicable) participating in this study will be maintained throughout the duration 
of this study on a Protocol Contact List form, incorporated herein by reference.  

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2  
INTRODUCTION: BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE                                     
2.1 
BACKGROUND INFORMATION  
Metastatic and recurrent endometrial cancer often carries a dismal long term prognosis with 
response rates of active chemotherapy or hormonal agents ranging between 20 to 35% [1].  While 
the search for curative agents is always a goal, maintenance therapy to prolong progression free 
survival (PFS) would have significant impact on patient care.  Currently median PFS in metastatic 
and recurrent endometrial cancer after first line chemotherapy in large phase III trials has been 
reported as 8.3 months in GOG 177 [1] and 14 months in GOG 209 [2]. Median overall survival 
(OS) in this patient population is 32 months as reported in GOG 209 [2]. In response to poor 
responses from known chemotherapy agents, targeted therapy has been the next logical line of 
research. 
PARP inhibitors are a newer drug class in gynecologic malignancy that have three separate drugs 
currently FDA approved in recurrent ovarian cancer, Olaparib, Rucaparib and Niraparib.  
Rucaparib has two approved indications; 1) for the treatment of adult patients with deleterious 
BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary 
peritoneal cancer who have been treated with two or more chemotherapies, and 2) for the 
maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary 
peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.  
PARP inhibition’s mechanism of action for cell death works by inhibiting single-strand DNA 
break repair by blocking the base excision repair pathway which ultimately leads to increased 
double-strand DNA breaks increasing cell death [3]. The increase in double-strand DNA breaks is 
also the mechanism for effectiveness of PARP inhibitors in BRCA positive and homologous repair 
deficient (HRD) patients seen in a multitude of trials in recurrent ovarian cancer   [4-8].  The 
BRCA tumor suppressor gene and HRD patients are deficient in the homolgous repair double-
strand DNA repair mechanism, leading to cell death via the principle of synthetic lethality of both 
single-strand base excision repair deficiency by PARP inhibition and HR repair deficiency by 
BRCA/HRD [9]. 
PARP inhibition for maintanaince therapy of recurrent ovarian cancer was first FDA approved for 
Olaparib based on 4 month PFS benefit seen in a trial known as Study 19 [Ledermann, 2012 
#1646].  Most recently Rucaparib has also been approved by the FDA for maintanaince therapy in 
recurrent ovarian cancer patients based on the results of the ARIEL 3 trial in which a PFS 
improvement of 11months was seen in BRCA positive patients, 8 months in HRD patients, and 5 
months in a separate intent to treat population [Coleman, 2017 #1655].   Rucaparib has been 
approved for maintanaince therapy in the recurrent setting, as well as third line therapy, with a 

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standard dosing regimen of 600mg BID based on a multitude of clinical trials that can be 
referenced in Table 1 of the investigators brochure. 
In the search for targeted therapy in the recurrent endometrial cancer  patient population, promising 
pre-clinical data is emerging for the most prevalent genetic alterations in endometrial cancer.  Loss 
of function of the tumor suppressor gene PTEN has been demonstrated in greater than 80% of 
endometrioid endometrial cancers [2].  PTEN loss of function is well known to lead to activation 
of the PI3K-AKT-mTOR pathway but has also been shown to lead to defects in homologous 
recombination (HR) DNA repair of double strand breaks [10].  Based on this mechanism, in vitro 
data on endometrial cancer cell lines has demonstrated sensitivity to PARP inhibitors.  Dedes, et 
al. have demonstrated that PTEN loss of function is associated with sensitivity to PARP inhibitors 
and lack of HR DNA repair, PTEN silencing leads to decreased RAD51 foci formation and 
sensitivity to PARP inhibition, and that the sensitivity of PARP inhibition in PTEN loss of function 
is independent of microsatellite instability (MSI) [11].  A case report of the use a PARP inhibitor 
in a PTEN-deficient endometrioid endometrial cancer demonstrated a significant disease response 
to therapy in a multi-recurrent patient who eventually recurred after 8 months of PARP inhibitor 
therapy and survived an additional 10 months after progression [12].  PARP inhibitors have shown 
significant responses in BRCA mutated breast and ovarian cancers, but early data is leading to 
potential clinical benefit in endometrial cancer patients from genetic mutations variant from 
BRCA.   
In addition to the potential benefit of PTEN deficient endometrial cancers, there may also prove a 
benefit in a variety of endometrial cancer histologies.  Ossovskaya et al. demonstrated a significant 
expression of PARP in uterine carcinosarcomas [13].  Intuitively this tumor type has high 
probability of responding to PARP inhibition as the epithelial component of these tumors is often 
serous which is the major tumor responder in HRD ovarian cancers.  Furthermore, Ghabreau et al. 
demonstrated a correlation between PARP-1 and progesterone receptor expression implying a 
potential role in PARP-1 expression in non endometrioid endometrial cancer formation [14]. 
As this therapy has proven efficacy in maintanaince therapy in the recurrent ovarian cancer 
population, based on the above preclinical data and mechanisms we believe there is potential 
benefit of maintanaince therapy in the recurrent endometrial cancer population as well. 
 
2.2 
RATIONALE/HYPOTHESIS 
The study population includes patients with stage III, stage IV, or recurrent endometrial cancer.  
This population is considered higher risk for progression and has an overall poor prognosis 
compared to early stage disease.  Historically, evaluation of this identical patient population has 
taken place in both GOG 177 and GOG 209 when looking at adjuvant chemotherapy regimens. 
GOG 177 evaluated the use of cisplatin and doxorubicin with or without paclitaxel (AP vs TAP) 

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[1].  TAP therapy was superior with more side effects but overall response rate was 57% and these 
patients had a PFS of 8.3 months and an OS of 15.1 months.  Complete response with TAP therapy 
was only 22%.  GOG 209 evaluated cisplatin, doxorubicin and paclitaxel vs. carboplatin and 
paclitaxel [15]. Interim analysis of these patients demonstrated non-inferiority of carboplatin and 
paclitaxel with a PFS of 14 months and a OS of 32 months.  Variation in the PFS in the same 
patient population has been attributed to the fact that GOG 177 inclusion criteria required 
measureable disease while GOG 209 did not.  GOG 209 data has not been fully matured only 
reported on as interim analysis abstract form to date and therefore this study estimates PFS of this 
patient population at 8 months based on the best fully published phase III data.  Using the existing 
literature of PARP inhibitor use in maintenance ovarian cancer we expect a PFS improvement of 
at least 4 months with maintenance therapy [4-6].  Second line chemotherapy for endometrial 
cancer has extremely low response rates of 9-26% [16].  Extending PFS through the use of 
maintenance therapy would have significant impact on this patient population.   
 
We expect the majority of patients enrolled on this trial will be those with stage III/IV disease who 
received a combination of surgery, radiation and chemotherapy consisting of carboplatin and 
paclitaxel based on GOG 209 and national practice patterns.  Standard practice patterns are for 
patients to receive 6 cycles of carboplatin and taxol for front line therapy though rarely patients do 
receive fewer or more cycles of therapy. Common reasons for patients to receive fewer lines of 
therapy would be progression or intolerance of therapy.  Common reason for patients to receive 
more lines of therapy would be partial response after 6 cycles and expected further clinical benefit. 
Therapy beyond 8 cycles with platinum based therapy is uncommon as platinum reactions typically 
occur after 8 cycles.  As this study aims to evaluate maintanaince therapy we attempt to control 
for variations in amount of prior chemotherapy regimen received affecting response rates  by 
incorporating this factor into our inclusion criteria.  Furthermore, as it is known that serous 
histology tumors are more aggressive with worse outcomes compared to endometrioid tumor types 
we plan to stratify on histology to ensure this does not affect our data for either arm of the study.  
We also plan to stratify on number of prior lines of therapy, 1 vs 2, to ensure PFS data is not 
affected by one arm weighted with more heavily treated patients.   This study is limited to 2 prior 
lines of therapy as significant clinical benefit in more heavily treated patient population is unlikely 
to be seen as well as PFS and OS data in patient populations beyond 2 lines is limited and expected 
to be low. 
 
There is currently no FDA approved therapy for second line treatment of endometrial cancer and 
NCCN guidelines incorporate a long list of optional therapies based on extensive evaluation of 
viable chemotherapy regimens.  There is no standard of care for this patient population but based 
on response rates, Adriamycin is considered the most efficacious and is the most common next 
line of therapy.  Limiting the acceptable number of prior lines of therapy, we would expect that 
the majority of recurrent patients would have received Adriamycin, Doxil, or the newly approved 
Pembrolizumab if MMR deficient.    

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Pembrolizumab was recently approved for treatment of adult or pediatric patients with solid tumor 
that have progressed following prior treatment and have unresectable or metastatic, microsatellite 
instability-high (MSI-H) or mismatch repair deficient tumors.  Previous data from GOG210 
demonstrate rates of MMR deficiency as high as 38% of all endometrial cancers, though clinical 
estimates are closer to a rate of 25% [Goodfellow, 2015 #1675]. There is currently no published 
data comparing use of any immunotherapy to other second or first line therapy options in recurrent 
endometrial cancer.  We do not believe there is any significant impact of MMR status on this study 
as there is no known association of PARP inhibition to MMR status, and as described above in 
preclinical data, MSI status was not associated with PARP sensitivity.  For this reason the prior 
use of Pembrolizumab is acceptable as a prior line of therapy and we expect patients who have 
received 2 prior lines of who are MMR deficient to have received this therapy. 
 
It is our hypothesis that PARP inhibition will have therapeutic benefit to the metastatic and 
recurrent endometrial cancer patient population.  We aim to demonstrate efficacy in terms of PFS 
and specifically hope to correlate with common mutational status. 
 
Hypothesis: We hypothesize that the use of PARP inhibitor maintenance therapy will improve PFS 
compared to placebo in patients with recurrent or metastatic endometrial cancer who have 
completed standard first line chemotherapy. 
 
2.3 
POTENTIAL RISKS AND BENEFITS  
Synthetic lethality has been exploited in several clinical studies with an oral PARP inhibitor in 
patients with BRCA-deficient tumor types. These studies evaluated the efficacy of continuous oral 
dosing of olaparib in women with gBRCA1 or gBRCA2 mutations, and either recurrent ovarian 
cancer or advanced breast cancer. [17] In these patients, who had received a median of 3 prior 
chemotherapy regimens, encouraging overall response rates of 33% and 41%, respectively, were 
observed in patients with a gBRCA mutation. A response rate of 24% was observed in ovarian 
cancer patients without evidence of a gBRCA mutation. [18] Activity in HGSOC has also been 
observed with switch maintenance therapy following response to platinum-based chemotherapy. 
[4, 19] Patients with platinum-sensitive relapsed ovarian cancer who achieved a response to 
another regimen of platinum-based chemotherapy followed by olaparib as switch maintenance 
treatment experienced a statistically significant improvement in median progression-free survival 
(PFS) (8.3 months) compared to patients who received placebo as maintenance therapy (4.8 
months); hazard ratio of 0.35 (95% confidence interval [CI], 0.25-0.49). [4] Patients with a BRCA 
mutation derived the most benefit (median PFS 11.2 vs. 4.3 months; hazard ratio, 0.18; 95% CI 
0.11-0.31; p < 0.00001). [19] In this study, the outcomes of somatic BRCA (sBRCA) mutant + 
gBRCA mutant patients were the same as gBRCA mutant patients alone, suggesting that it is 
appropriate to not differentiate between germline and somatic mutations. Patients without a BRCA 

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mutation also experienced significant benefit from treatment with olaparib (hazard ratio, 0.53; 95% 
CI 0.33-0.84; p = 0.007). [19] 
 
Based on clinical data of olaparib as treatment for mCRPC patients with predicted loss-of-function 
alterations in HRR genes such as BRCA1/2 and ATM, [20] rucaparib may also be a compelling 
therapy for the treatment of patients with this disease. A response rate of 88% (14 of 16 patients) 
was reported in mCRPC patients who received olaparib and in whom next generation sequencing 
(NGS) identified homozygous deletions, deleterious mutations, or both in DNA-repair genes, 
including BRCA1/2, ATM, Fanconi’s anemia genes, and checkpoint kinase 2 (CHEK2). Taken 
together, nonclinical and clinical data indicate that benefit from PARP inhibitor treatment may 
extend beyond patients with BRCA mutations and support the investigation of PARP inhibitors in 
a broader group of patients with HRD.  Currently, Rucaparib is FDA approved as monotherapy 
for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated 
advanced ovarian cancer who have been treated with two or more chemotherapies. 
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Reference safety information of Rucaparib is available in the Investigators Brochure version 10.0 
Section 6.6 and Table 19.  Adverse drug reactions presented in the investigators brochure have 
been extracted from pooled safety data from 917 patients treated with rucaparib in either 
placebo-controlled Study CO-338-014 (ARIEL3) or one of two open-label, single-arm trials 
(Studies CO-338-010 and CO-338-017 [ARIEL2]). All 917 patients had either epithelial ovarian 
cancer, fallopian tube cancer, or primary peritoneal cancer and initated rucaparib at a dose of 600 
mg BID. The safety profiles were comparable across the 3 studies.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
The risks to participants are reasonable in relation to the anticipated benefits to participants and/or 
society, and in relation to the importance of the knowledge that may reasonably be expected to 
result, thereby falling in favor of performing the study: 
• To Participant: Participants will be helping study a maintenance therapy for 
women with endometrial cancer.  Rucaparib has shown success in increasing 
progression free survival in women with ovarian cancer.  Currently there is not 
an FDA approved maintenance therapy for women with recurrent and/or 
metastatic endometrial cancer.     
• To Society: Rucaparib has proven both safety and efficacy in improving the 
progression free interval for women with ovarian cancer. Results from this 
study will support future changes to NCI guidelines in this patient population 
and future phase III studies.   

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• Justify the importance of the knowledge gained: Maintenance therapy prolongs 
a patient’s time before recurrence and reduces exposure to cytotoxic 
chemotherapy agents.  This study will provide preliminary efficacy data and 
genetic response for treating women with recurrent/metastatic endometrial 
cancer.  
 
3 
OBJECTIVES AND PURPOSE 
Primary objective: To measure progression free survival (PFS) with the use of Rucaparib 
compared to placebo in women with recurrent or metastatic endometrial cancer after first line 
chemotherapy. 
Secondary objectives:  
1. To measure overall survival (OS) with the use of Rucaparib compared to placebo in women 
with recurrent or metastatic endometrial cancer after first line chemotherapy. 
2. To determine the efficacy with the use of Rucaparib compared to placebo in women with 
recurrent or metastatic endometrial cancer after first line chemotherapy as measured by 
overall response rate (ORR) in patients with measurable disease. 
3. Safety and tolerability. Safety endpoints including incidence and severity of adverse events 
and significant laboratory abnormalities.  
Tertiary/Exploratory objectives: 
1. To preliminarily assess the efficacy with the use of Rucaparib compared to placebo in 
women with recurrent or metastatic endometrial cancer after first line chemotherapy in 
relation to HRD, BRCA, PTEN, PIK3CA and AKT. 
 
4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
This is a phase II, randomized, double-blind, trial for the use of Rucaparib as maintenance therapy 
in metastatic and recurrent endometrial cancer.  Eligible patients will have received 1 to 2 prior 
lines of cytotoxic therapy and surgery or radiation, if appropriate, prior to randomization.  At 
completion of cytotoxic therapy patients who have demonstrated complete response or partial 
response will be eligible for randomization. Response to prior line of therapy will be classified 
based on RECIST 1.1 criteria.  Patients with no RECIST 1.1 measurable disease at baseline scan 
will be considered complete response (CR) from prior therapy.  Patients with RECIST 1.1 
measurable disease will be compared to prior available imaging to categorize as partial response, 

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progressive or stable disease related to that line of therapy.  If no comparable prior imaging is 
available for comparison patient will be included at investigator’s discretion for progressive 
disease and categorized as unknown response to prior therapy. 
Patients will be randomized in a 1:1 fashion to receive Rucaparib 600mg twice daily vs. placebo 
continuously on a 28-day cycle until disease progression or other indication for discontinuation.  
Patients will be evaluated for progression of disease by history and physical exam every cycle as 
well as radiologically by CT imaging of chest/abdomen/pelvic every three cycles.  Patients will be 
followed per study protocol from C1D1 for secondary outcomes. 
 Randomization will be stratified according the following criteria to ensure equivalent patient 
populations in Arms A & B; 1) Tumor histology of endometrioid, serous and other, 2) Number of 
previous lines of therapy, 1 or 2. 
The study is designed as a 2-arm prospective superiority randomized clinical trial (RCT) with the 
following 2 treatment arms: 
Arm A: Rucaparib 600 mg BID for 28 days 
          Arm B: Placebo 600 mg BID for 28 days 
Study subjects will be randomized to the treatment arms in a 1:1 ratio.  Patients and investigators, 
will be blinded to the randomization arms. Randomization schemas will be provided by study 
statisticians at the University of Colorado not involved in the randomization and collection of study 
data.  
Treatment Duration: Chemotherapy cycles every 4 weeks (+/- 3 days) until progression of 
disease 
Study duration including follow-up: 24 months following progression of disease  
4.2 
STUDY ENDPOINTS 
 
4.2.1 PRIMARY ENDPOINT 
• Progression free survival (PFS)  
The primary endpoint of this study is progression free survival (PFS).   
Progression free survival is defined as cycle 1 day 1 (C1D1) till the time of progression as 
determined by RECIST 1.1 criteria or death. 
 
4.2.2 SECONDARY ENDPOINTS 
• Overall Survival  
Overall survival (OS) will be measured through routine follow-up.   

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• Overall survival is defined as cycle 1 day 1 (C1D1) till the time of death.  
 
• Toxicity 
Toxicity will be assessed at cycle day 1 of each study cycle and day 28 following completion 
of therapy. Evaluation will include incidence and severity of adverse events and significant 
laboratory abnormalities.  For laboratory parameters (CBC and CMP), changes of laboratory 
values over time (e.g., change from baseline summary statistics), grade shifts in laboratory 
values from baseline to worst on-study value, and grade 3 or higher toxicities a dose 
modification will be considered.  If worsening of the condition persist after sufficient dose 
modification, the subject will be evaluated at start of next treatment cycles and may be removed 
from the study per provider’s discretion.  
1.2.3 EXPLORATORY ENDPOINTS 
• Disease response in relation to molecular measures of BRCA and HRD status as well as 
mutational status of  PTEN, PIK3CA,  and AKT. 
The association between disease response (measured in a binary manner as “responded” or 
“did not respond”) and several molecular measures (BRCA, HRD, PTEN, PIK3CA, AKT) will 
be explored.  Archival tissue from the initial occurrence of disease and/or plasma collected on 
enrollment will be used to abstract these tumor markers.   
 
 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
PARTICIPANT INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
1. Provision to sign and date the consent form. 
2. Stated willingness to comply with all study procedures and be available for the duration of 
the study. 
3. Be a female aged 18-89.  
4. Patients with a primary Stage III/IV or recurrent endometrial cancer 
5. Patients have received at least one prior chemotherapy regimen and no more than two prior 
cytotoxic regimens (including hormonal therapy) 
6. Primary chemotherapy regimen must have consisted of at least 4 completed cycles and no 
more than 8 completed cycles 
7. Previous cytotoxic or radiation regimen at least 4 weeks  before initiation and no more than 
8 weeks from initiation after last dose of previous therapy 

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8. Patients who receive radiation to the whole pelvis or at least 50% of the spine must 
complete radiation therapy and have at least 4 weeks’ time elapse prior to initiation of drug  
9. ECOG performance status of 0, 1 or 2 
10. ANC  1500 cells/L 
11. Platelet count > 100,000 L 
12. Hemoglobin  9.0 g/dL 
13. Serum albumin  2.5 g/dL 
14. Total bilirubin ≤ 1.5 x ULN 
15. AST and ALT ≤ 3.0 x ULN 
16. Serum Creatinine ≤ 1.5x ULN 
 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
1. Inability to comply with study and follow-up procedures 
2. Significant cardiovascular disease, such as New York Heart Association cardiac disease 
(Class II or greater), myocardial infarction within the past 3 months, unstable arrhythmias, 
or unstable angina 
3. Known clinically significant liver disease defined as AST and ALT > 3.0 x ULN and/or 
Total bilirubin ≥ 1.5 x ULN, or documented history of active viral, alcoholic, or other 
hepatitis, cirrhosis, and inherited liver disease 
4. Participation in investigational clinical trial within last 30 days  
5. History of significant chronic disease including HIV/AIDS or hepatitis C 
6. Inability to provide informed consent 
7. Known CNS malignancy or CNS metastases 
8. Patients with previous malignancy, other than endometrial, within the past 2 years from 
cycle 1, day 1, with the exception of those with negligible risk of mestastasis or death, such 
as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or 
carcinoma in situ of the breast. 
9. History of stroke or transient ischemic attack (TIA) within 3 months prior to cycle 1 day 
1(C1D1) 
10. Women with prognosis for survival less than 6 months 
11. Patients who have progressed or have stable disease (SD) through most recent 
chemotherapy regimen 
12. Patients deemed otherwise clinically unfit for clinical trial per Investigator’s discretion 
13. Patients with duodenal stent or other GI disorder/defect that would interfere with 
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14. Female patients who maintain fertility potential and refuse to comply to use contraception 
and be followed for pregnancy by pregncany testing 
15.  Minor surgical procedure <=14 days or major surgeries <=28 days prior to first dose of 
treatment 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Potential subjects will be identified and recruited from the investigators’ clinical practice in 
gynecologic oncology.  Potential subjects will present to clinic after completing chemotherapy for 
endometrial cancer and will not have shown progression at the time of enrollment.  
Subjects who enroll in study will do so in accordance with their standard of care surveillance for 
their disease.  This includes a surveillance visit and CT exam to assess recurrence every 3 months.  
Patients who are on therapy for their disease will be seen more frequently (at the start of each new 
cycle of therapy), per standard of care.  Participants who conclude treatment early will be followed 
by phone and/or medical records at the completion of study.  
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
Participants are free to withdraw from participation in the study at any time upon request. 
Reasons other than progression for study discontinuation can be due to patient desire, adverse 
events, or for any reason deemed appropriate by the investigator and/or sponsor.   
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
Participant will be discontinued from study if exhibiting continuing/worsening adverse or toxic 
events not improved with dose modification of the study therapy or for any other contraindication 
to the assigned treatment.  End of treatment visit will be conducted at time participant is 
discontinued from the study.   Reason for discontinuation should be documented on the early 
discontinuation CRF.   
For participants discontinued from the study early, they will resume normal medical care. 
Treatment of any persisting adverse event will be per standard of care.  If participant stops taking 
their medication prior to being discontinued or ending treatment by the investigator, they may be 
discontinued from the study and asked to return to the clinic for an end of treatment assessment.  

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6 
STUDY AGENT 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
Rucaparib (CO-338) is a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) 
polymerase (PARP) being developed for the treatment of cancer associated with homologous 
recombination deficiency (HRD). Rucaparib has been shown to potently inhibit PARP-1, PARP-
2, and PARP-3 and has demonstrated activity in cells, animal models and patients with a breast 
cancer gene 1 or 2 (BRCA1 and BRCA2) mutations in both clinical and nonclinical studies. Clovis 
Oncology, Inc. (Clovis) is developing rucaparib for oral administration in patients with advanced 
ovarian cancer and metastatic castration-resistant prostate cancer (mCRPC) associated with HRD, 
including patients with a deleterious mutation in BRCA1, BRCA2 and other HR gene mutations. 
 
6.1.1 ACQUISITION 
 
Rucaparib camsylate (also known as CO-338; formerly known as PF-01367338-BW and AG-
014447) is an oral formulation with a molecular weight of 555.67 Daltons. Rucaparib tablets for 
oral administration will be supplied to the study sites by Clovis Oncology. The starting dose of 
rucaparib is 600 mg ingested BID. A brief description of the investigational product is provided 
below. 
 
Drug Name: 
Rucaparib  
INN: 
Rucaparib 
Formulation: 
(strengths expressed 
as free base) 
Tablet; film coated; 200 mg (blue, round, debossed with C2), 
250 mg (white, rounded diamond shape, debossed with C25), 
300 mg (yellow, oval, debossed with C3) 
How Supplied: 
200, 250, and 300 mg (as free base) strength tablets in 60 
count HDPE  bottles with child-resistant caps. Patients may 
receive one or more strengths. 
Storage Conditions: 
15 to 30° C (59 to 86° F). 
 
 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Rucaparib 
The oral formulation of rucaparib contains the camphorsulfonic acid salt of the active agent 
rucaparib. All dosage strengths are expressed as the weight of free base rucaparib. Three strengths 
of oral rucaparib, 200 mg, 250 mg, and 300 mg are available as immediate-release film coated 
tablets. The 200 mg, 250 mg, and 300 mg tablets all contain the same ratios of active agent and 
excipients, with different strengths achieved by increasing the tablet weight.  

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The physical appearances of the tablets are unique in order to ensure proper identification. The 
200 mg tablets are blue, round (11 mm) tablets de-bossed with ‘C2’. The cosmetic blue film 
coating is Opadry II containing polyvinyl alcohol, titanium dioxide, polyethylene glycol/macrogol, 
talc, FD&C Blue #1 colorant, brilliant blue FCF aluminum lake, and FD&C blue indigo carmine 
aluminum lake. The 250 mg tablets are white, diamond shaped (15 mm x 11 mm) tablets de-bossed 
with ‘C25’. The cosmetic white film coating is Opadry II containing polyvinyl alcohol, titanium 
dioxide, polyethylene glycol/macrogol, and talc. The 300 mg tablets are yellow, oval tablets (16 
mm x 8 mm) de-bossed with ‘C3’. The cosmetic yellow film coating is Opadry II containing 
polyvinyl alcohol, titanium dioxide, polyethylene glycol/macrogol, talc, and irradiated yellow iron 
oxide. 
Placebo Tablet  
Placebo tablets to match active tablets are available in all doses (200 mg, 250 mg, and 300 mg). 
These are identical in appearance and weight to the active tablets and contain the same excipients, 
but no active agent. Packaging and storage conditions are identical to the active tablets. Placebo 
tablets for oral administration will be supplied to the study sites by Clovis Oncology. 
6.1.3 PRODUCT STORAGE AND STABILITY 
 
All tablets are provided in high-density polyethylene (HDPE) bottles with child-resistant caps 
and should be stored in the provided containers between 15º and 30ºC (59 to 86° F). 
 
6.1.4  PREPARATION 
 
Rucaparib (formerly known as AG-014447 and PF-01367338) refers to the free base. The 
camphorsulfonic acid salt form (also referred to as camsylate) CO-338 (formerly known as PF-
01367338-BW) is used in the clinical studies. CO-338 is formulated into a tablet for oral dosing. 
PF-01367338-09, a lyophilized powder for IV injection, and a glucuronate salt, PF-01367338-AU, 
were also developed and used in previous studies, but are no longer in development. 
 
 
Camphorsulfonic acid salt form of rucaparib (CO-338, formerly known as 
PF-01367338-BW) 
Laboratory Code: CO-338 (formerly known as PF-01367338-BW) 
Molecular Weight: 555.67 Daltons (Da.) 
IUPAC Name: 8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-
azepino[5,4,3-cd]indol-6-one((1S,4R)-7,7-  
dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt 
Molecular Formula: C19H18FN3O-C10H16O4S 
Physical Description: White to pale yellow powder 
 

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6.1.5 DOSING AND ADMINISTRATION 
 
Rucaparib should be taken orally at 600 mg BID.  Rucaparib tablets, or the equivalent of placebo, 
will be dispensed to the patient in sufficient quantity to last until Day 1 of the next treatment cycle. 
Medication will be provided in a blinded medication bottle dispensed from the investigational 
pharmacy. Patients will ingest the assigned treatment pill twice daily at about the same time every 
day as close to 12 hours apart as possible. Rucaparib should be taken with at least 8 oz. (240 mL) 
of room temperature water with or without food. Patients will keep all unused tablets and 
containers (empty, partially used, and/or unopened) for accountability at the next visit. In the event 
of toxicities, re-treatment or dose modification will be according to the criteria described below.  
 
6.1.6 ROUTE OF ADMINISTRATION 
Oral 
 
6.1.7 STARTING DOSE AND DOSE ESCALATION SCHEDULE 
 
The recommended starting dose of rucaparib as continuously administered oral monotherapy is 
600 mg BID. This dose will not be increased for the purpose of this study.   
6.1.8 DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS 
 
Dose reductions will be permitted for any SAE as listed in section 8, or any grade 3 AE at the 
discretion of the investigator. Reduction will be based on the following algorithm.  Supportive 
care will be at the discretion of the investigator.  The use of GCSF will be permitted.   
 
Dose Reduction 
Dose 
Starting Dose 
600 mg twice daily (two 300 mg tablets)  
First Dose Reduction 
500 mg twice daily (two 250 mg tablets) 
Second Dose 
Reduction 
400 mg twice daily (two 200 mg tablets)  
Third Dose Reduction* 300 mg twice daily (one 300 mg tablet)  
* 
Consult with investigator-sponsor before reducing to dose level 3. Further dose reduction may be 
possible, but require consultation with the investigator-sponsor. 
Treatment Hold Criteria 
Treatment with rucaparib should be held if any of the following are observed and a dose reduction 
should be considered or implemented.  
• Grade 3 or 4 hematologic toxicity 
• Grade 3 or 4 non-hematologic toxicity (except for alopecia, nausea, vomiting, or diarrhea 
adequately controlled with systemic antiemetic/antidiarrheal medication administered in 
standard doses according to the study center routines). Grade 3 or Grade 4 ALT/AST 
elevations should be managed as described below.  

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• In addition, and at the discretion of the investigator, the dose of rucaparib may be held 
and/or reduced for Grade 2 toxicity not adequately controlled by concomitant medications 
and/or supportive care. 
Rucaparib Re-Treatment Criteria 
Treatment may resume if:  
• ANC ≥ 1.0 x 109/L  
• Platelet count ≥ 100 x 109/L 
• Non-hematologic toxicities have returned to baseline or ≤ CTCAE Grade 1 severity (or, at 
the investigator’s discretion, ≤ CTCAE Grade 2 severity if not considered a safety risk for 
the patient). Grade 3 or Grade 4 ALT/AST elevations should be managed as described 
below. 
 
6.1.9 MANAGEMENT OF RUCAPARIB TREATMENT-EMERGENT SAES 
REQUIRING DOSE REDUCTIONS 
 
Management of Anemia including evaluation for MDS/AML and follow-up of patients who 
discontinue treatment with ongoing anemia: 
• If the patient develops anemia CTCAE Grade ≥ 3,  treatment should be held until the 
anemia improves to CTCAE Grade ≤ 2 whereupon daily dosing may then be resumed at 
either the same dose or a lower dose, per investigator discretion. 
• If the duration of dosing is interrupted for > 14 consecutive days due to anemia CTCAE 
Grade ≥ 3, treatment should be permanently discontinued, unless otherwise agreed between 
the investigator and the sponsor. 
• In addition, if anemia CTCAE Grade ≥ 3 persists for > 14 consecutive days, or a 
dependence upon blood transfusion occurs, then weekly complete blood counts should be 
performed until resolution of the event.  
• If the anemia has not improved to CTCAE Grade ≤ 1 then the patient should be referred to 
a hematologist and analysis of the bone marrow with cytogenetic studies are recommended 
according to standard hematologic practice. 
• The bone marrow analysis should include a bone marrow aspirate (for cellular morphology, 
cytogenetic analysis, and flow cytometry) and a core biopsy (for bone marrow cellularity). 
Management of ALT/AST Elevations: 
Grade 3 ALT/AST elevations have been successfully treated with treatment interruption and/or a 
reduction in dose. The data reported as of the data cut-off date suggest that many patients have 
been able to continue treatment with 600 mg BID following a dose interruption, without any further 
elevation or recurrence of Grade 3 ALT/AST. The following guidelines have been suggested for 
managing Grade 3/4 ALT/AST elevations. 
 

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* 
Grade 4 ALT/AST elevations: hold treatment until values have returned to Grade 2 or 
better, then resume treatment with a dose reduction. Monitor liver function tests weekly 
for 3 weeks after treatment has been restarted. 
 
* 
Grade 3 ALT/AST elevations, in the absence of other signs of liver dysfunction, should be 
managed as follows: 
o Monitor liver function tests weekly until resolution to ≤ Grade 2. 
o Continuation of treatment with elevation of ALT/AST up to Grade 3 is permitted 
provided bilirubin is < ULN and alkaline phosphatase is < 3 x ULN. 
o If patient has Grade 3 ALT/AST and continues on treatment, and levels do not 
decline within 2 weeks or they continue to rise, treatment interruption and 
resolution to ≤ Grade 2 will be required before treatment can be resumed, either at 
the current dose or at a reduced dose. 
Management of Myelosuppression:  
 
Grade 3/4 myelosuppressive events have been successfully treated with supportive care and dose 
interruption/reduction. Additional diagnostic evaluation, including bone marrow examination, 
should be considered for patients with persistent myelosuppression that does not stabilize or 
recover with treatment modification. 
Dose re-escalation upon improvement of toxicity to ≤ CTCAE Grade 1 is permitted at the 
discretion of the investigator. 
 
6.1.10 DURATION OF THERAPY 
Duration of study therapy will be until progression of disease as determined by treating provider 
in agreement with local study PI.  In the event that treating provider and local PI do not agree, 
national study PI will determine progression status. 
 
6.1.11 TRACKING OF DOSE 
 
Dose modifications will be tracked on the case research form (CRF) at time of event.  
Medication adherence will be calculated by return of unused medication at the completion of each 
treatment cycle.   
 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 
The institutional pharmacy is responsible for managing the inventory of rucaparib for the IIT.  
Rucaparib supply shipments from Clovis, or its designee to the pharmacy will be made on an 
agreed upon schedule based on enrollment in the IIT. 
 
6.2.1 RECEIPT OF STUDY DRUG  

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Clovis oncology will provide study sites with blinded drug kits to be supplied to the patient via the 
site investigation drug pharmacy.  Rucaparib supplies will be shipped to the address and attention 
of:  Principal Investigator or designee, and the institution pharmacist or designee.  If this address 
or contact person should change, please inform Clovis so that the records can be updated and 
shipments are redirected to the appropriate location/study personnel.  
 
Please follow the instructions below when receiving study drug at your site: 
Step 1:  Upon receipt, the rucaparib investigational product shipping box should be immediately 
opened, and the STEMS monitor located and reviewed. 
Step 2:  Upload the STEMS monitor information at www.almacstems.com. 
Step 3:  Upon upload of the STEMS monitor information, print the temperature report and file 
with the rucaparib investigational product documents. 
Step 4:  If the STEMS monitor is not displaying an alarm, the rucaparib investigational product 
supplies are ready to be used.  Please store the supplies in a temperature-controlled, locked, 
limited-access area.  Proceed to Step 6. 
Step 5:  If the STEMS monitor displays an alarm, please: 
▪ 
Quarantine the rucaparib supplies in a temperature-controlled, locked, limited-access area 
until further notice from Clovis. 
▪ 
Send an email to Rucasupply@clovisoncology.com indicating that a rucaparib shipment 
has   been received and the temperature monitor is displaying an alarm. 
▪ 
A Clovis Oncology clinical supply team member will be in touch with further instructions 
Step 6:  After the STEMS monitor has been registered with Almac and the temperature report 
printed, the monitor may be destroyed. 
▪ 
Please note that the STEMS monitor has a lithium battery in it, so it should be disposed of 
in a manner compliant with local regulations. 
 
6.2.2 REPORTING OF DAMAGED, MISSING, OR LOST STUDY DRUG 
Please follow the instruction below when study drug is noted as damaged or missing at the site or 
with patient. This process also applies if study drug was lost or misplaced by a patient. 
Damaged or Missing upon receipt of a shipment  If study drug tablets or study drug bottles are 
observed to be damaged or missing upon receipt, please notify your MSL and Clovis Supply Chain 
(RucaSupply@ClovisOncology.com) within 48 hours by completing and submitting the provided 
Investigational Product Incident Report Form to trigger an investigation, if required.   
Please contact Clovis Supply Chain and your MSL prior to destroying any damaged, expired or 
end of study drug. The pharmacist or designee must complete and submit the Study Drug 
Destruction Authorization Form to Clovis for those three cases only to obtain approval from 
Clovis before destruction.  Standard returns and empty bottles may be destroyed per site SOPs, 

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after all site drug accountability is completed. All drug destruction certifications and 
documentations should be stored in study files at the site.  
If the study drug must be destroyed, please follow the instructions listed in the Destruction of 
Study Drug.  
Damaged during site storage If study drug tablets or study drug bottles are noted as damaged 
while being stored at the site, please complete the Investigational Product Incident Report 
Form and send to your MSL and Clovis Supply Chain (RucaSupply@ClovisOncology.com) within 
48 hrs. of knowledge of the issue to obtain further instructions.   
Clovis Supply Chain will conduct an investigation and determine whether the bottle(s) is still 
usable or should be destroyed.  
If the study drug must be destroyed, please follow the instructions listed in the Destruction of 
Study Drug.  
Missing during site storage If study drug goes missing during site storage, please complete the 
Investigational Product Incident Report Form and send to your MSL and Clovis Supply chain 
(RucaSupply@ClovisOncology.com) within 48 hrs. of knowledge of the issue to obtain further 
instructions.   
Bottles or tablets are damaged during patient use If the study drug tablet(s) is damaged or the 
bottle tamper seal is damaged or missing after being provided to the patient, you must collect the 
damaged bottle(s) from the patient and complete an Investigational Product Incident Report 
Form.  
If the study drug must be destroyed, please follow the instructions listed in the Destruction of 
Study Drug and follow your local requirements.  
Bottles missing during patient use If a bottle or bottles of study drug go missing after being 
provided to the patient, additional bottle(s) should be dispensed from the current drug supply, and 
documented on the drug accountability record. If needed, please contact Clovis Supply Chain by 
email (RucaSupply@clovisoncology.com). 
Individual tablets damaged or missing during patient use If individual tablets are damaged or 
go missing during patient use, an additional bottle should be dispensed from the current drug 
supply, and documented on the drug accountability record. If needed, please contact Clovis Supply 
Chain by email (RucaSupply@clovisoncology.com). 
6.2.3 DISPENSATION OF STUDY DRUG  
 
Please follow the instructions below when dispensing study drug at your site: 
▪ 
Determine quantity of bottles and strength to dispense to each patient. 

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▪ 
Complete the provided IIT Investigational Product Patient Dispensing Log or equivalent 
log. 
 
6.2.4 TEMPERATURE EXCURSIONS OF STUDY DRUG  
 
Please follow the instructions below when an excursion occurs while study drug is stored at your 
institution:  
▪ 
Clovis permits allowable excursions; refer to Clovis Allowable Excursion memo for 
01Dec2015 for details. Should the excursion fall within the allowable range, site may proceed 
to use product after documenting excursion in site logs and records. There is no need to contact 
Clovis unless the excursion falls outside the instance and cumulative range on the memo. 
▪ 
If the excursion is outside allowable range, segregate affected supply in a location separate 
from any unaffected study drug. Clearly mark study drug in question as “Quarantined” to 
ensure it is not used while excursion is being evaluated and follow the remaining 3 bullets 
below. 
▪ 
Notify Clovis Supply Chain as soon as possible after the excursion is. All storage temperature 
excursions affecting study drug, regardless of whether Clovis authorization for continued use 
is allowed, should be clearly documented in temperature logs or other appropriate documents 
maintained at the site. 
▪ 
Complete the provided Investigational Product Incident Report Form and send to Clovis 
Supply Chain (RucaSupply@ClovisOncology.com) and to your MSL via email within 24-48 
hours of excursion being identified, along with complete temperature logs or recordings for 
duration of excursion.  If all study drug is affected and site has ongoing patients, submit form 
to Clovis immediately.   
▪ 
Following an assessment by Clovis Supply Chain, notification of the final disposition of the 
study drug will be sent to the site accordingly. 
 
6.2.5 DESTRUCTION OF STUDY DRUG  
 
It is expected that returned, unused by assigned patient, damaged, expired or otherwise out of 
specification study drug will be destroyed by the site, using internal site procedures for the safe 
disposal of cytotoxic materials.   
 
6.2.6 SITE DRUG ACCOUNTABILITY AND RECONCILIATION  
 
NOTE: Drug accountability is an Investigator GCP requirement for IITs.  All participating 
institutions must retain copies of all study drug inventory records, packing lists, and other 
shipping documents (e.g. invoices and receipts upon delivery from the study drug depot), 
prescriptions for dispensing, delivery cartons, etc. for accountability of the drug.  
Accountability should be ongoing per pharmacy and protocol requirements, as applicable.  

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Physical product inventories should be routinely reconciled against study accountability logs.  If 
any discrepancies are identified, pharmacy personnel must attempt to reconcile all such 
discrepancies.  The discrepancies should be clearly explained in the accountability logs or other 
appropriate documentation, and the process of reconciliation and resolution must be clearly 
documented.   
The provided IIT Investigational Product Temperature Log, IIT Investigational Product 
Patient Dispensing Log, and IIT Investigational Inventory Log are tools which can be used to 
document accountability.  Site-created logs/accountability documents may be used instead of the 
Clovis-supplied logs.   
The pharmacist or other appropriate site personnel should document in the site’s pharmacy 
accountability record/log each time study drug is: 
▪ Received from the drug depot  
▪ Dispensed to a study patient  
▪ Subjected to a temperature excursion 
▪ Returned / Quarantined / Missing / Damaged / Destroyed 
 
7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATION 
Treatment will include Rucaparib 600mg PO BID in arm A vs placebo pills PO BID in arm B to 
be taken on a daily basis on a 28-day cycle until disease progression or other indication for study 
discontinuation.  Reasons other than progression for study discontinuation can be due to patient 
desire, adverse events, or for any reason deemed appropriate by the investigator and/or sponsor.  
Discontinuation of therapy for greater than 28 days due to AE’s will also result in discontinuation 
of study.  Initiation of treatment must occur between 4 and 8 weeks of last dosing of prior therapy. 
The treatment period is cycles of 28 days until progression of disease.  Patients will be evaluated 
at the beginning of every cycle and will undergo CT imaging of the chest, abdomen and pelvis at 
the completion of every 3 cycles (+/- 7 days) for evaluation of progression of disease and adverse 
events. Progression will be classified based on RECIST 1.1 criteria.  If a patient has been on study 
24 months, patient evaluations may be decreased to every 3 cycles at the providers discretion. 
7.1.1 CLINICAL ASSESSMENTS  
 
ECOG performance status 
 
ECOG Score 
Criterion 
0 
Fully active, able to carry on all pre-disease performance without restriction 

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1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed 
or chair 
5 
Dead 
 
 
RECIST 1.1 guidelines for tumor response [21] 
 
Evaluation of Target lesions 
Complete Response (CR)  
Disappearance of all target lesions 
Partial Response (PR)  
At least a 30% decrease in the sum of the LD of target lesion, 
taking as reference the baseline sum LD 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR not sufficient 
increase to qualify for PD, taking as reference the smallest sum 
LD since the treatment started 
Progressive Disease (PD) 
At least a 20% increase in the sum of LD of target lesions, 
taking in reference the smallest sum LD recorded since the 
treatment started or the appearance of one of more new lesions 
Evaluation of Non-target lesions 
Complete Response (CR) 
Disappearance of all non-target lesions and normalization of 
tumor marker levels 
Incomplete Response/Stable 
Disease (SD) 
Persistence of one or more non-target lesions 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 
 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
7.2.1 CLINICAL LABORATORY EVALUATIONS (RESEARCH 
PROCEDURES) 
Samples for hematology, serum chemistry, and serum pregnancy will be analyzed by a local 
laboratory. The panels of laboratory tests to be performed are shown below: 
Hematology (CBC): red blood cells (RBC) and parameters (hemoglobin, hematocrit, mean 
corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], and mean corpuscular 
hemoglobin concentration [MCHC]), white blood cells (WBC) and differential (with ANC), and 
platelet count will be assessed at screening, during treatment at each study visit, and at the 

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treatment discontinuation visit for all patients. Hematology results must be reviewed by the 
investigator before the start of treatment with study drug and ongoing at times testing occurs. 
Additional and more frequent tests may be performed at the investigator’s discretion. 
Serum Chemistry (CMP): total protein, albumin, creatinine or estimated GFR using the 
Cockcroft Gault formula, BUN or urea, total bilirubin, alkaline phosphatase (ALP), ALT, AST, 
glucose, sodium, potassium, chloride, CO2, and calcium), at screening, during treatment at each 
study visit, and at the treatment discontinuation visit for all patients. Fasting is not required before 
blood sampling. Serum chemistry results must be reviewed by the investigator before the start of 
treatment with study drug and ongoing at times testing occurs. 
Lipid Profile: total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-
density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) at baseline (C1D1) 
and at the treatment discontinuation visit for all patients. Fasting is not required before blood 
sampling.  
Serum Pregnancy: for women of childbearing potential only. A serum pregnancy test must be 
performed ≤ 3 days prior to first dose of study drug (a negative result is required before dosing can 
begin) and at the treatment discontinuation visit (unless the woman has undergone surgical 
menopause by hysterectomy). A serum pregnancy test must be performed ≤ 3 days prior to Day 1 
of every cycle during the Treatment Phase, and a serum pregnancy test performed at Treatment 
Discontinuation. A positive serum pregnancy test during study participation must be reported to 
the Sponsor. Refer to section below (Pregnancy or Drug Exposure during Pregnancy) for details. 
Laboratory reports will be reviewed by the investigator or delegated physician who will then 
comment on out-of-range parameters and assess clinical significance. Clinically significant 
abnormalities and associated panel results, as well as results of any additional tests performed as 
follow-up to the abnormalities, will be documented on the eCRF as an AE. Refer to Section 10.5 
for guidelines on reporting of abnormal laboratory values as AEs. 
7.2.2 OTHER ASSAYS OR PROCEDURES (RESEARCH) 
 
Tumor genetic screening of DNA extracted from microdissected tumor tissue will be used to test 
for mutations in the study genes of interest: HRD, BRCA, PTEN, PIK3CA and AKT. [22]  
Tumor will be collected from surgical pathology specimans using archival tissue (initial tumor 
specimen) or recent current disease biopsy (when available). Plasma will be collected on C1D1.  
 
7.2.3 SPECIMEN PREPARATION, HANDLING, AND STORAGE 
 
Collection of blood at the baseline visit (C1D1) will be used as source for germline DNA. 
Collection may be used for further future DNA analysis.  Collection kits provided by the University 
of Colorado Biorepository Core Facility will be used for the blood collection. Blood collected at 
University of Colorado will be processed by the Biorepository. Blood from external sites will be 

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processed locally and shipped to the Biorepository, provided collection kits include all the 
components to process, aliquot, and store blood specimens. Archival formalin-fixed paraffin-
embedded (FFPE) tissue from diagnostic and/or surgical procedures will be used for the extraction 
of tumor DNA for future mutation analysis. Archival FFPE specimens will be requested from the 
participating sites and where needed the participating sites will retrieve the materials from 
secondary sites where procedures where performed. Preferably a representative tissue block will 
be submitted but in cases where release of a block is prohibited submission of 15 unstained tissue 
sections will be accepted. After the archival FFPE specimens are received by the Biorepository 
specimens data will be logged in the database and transferred to the Colorado Molecular Pathology 
Shared Resource (CMCO) laboratory for sectioning, pathological evaluation, macrodissection (if 
needed), and DNA extraction. Where possible 15 blanks section will be prepared for banking and 
future research studies. After DNA extraction the FFPE blocks will be transferred to the 
biorepository to be returned to the originating site. Representative H&E slides of the specimens 
will provided to the Biorepository for digital imaging to create a permanent research record. Data 
on processing and DNA metrics will be recorded in the database. Specimens will be stored for 
future use. 
 
7.2.4 SPECIMEN SHIPMENT 
 
Archival specimen shipping kits will be provided to the external sites for transfer of the FFPE 
materials. The specimen shipping kits will contain all the materials needed to pack and ship the 
blocks and/or slides to the biorepository. The Biorepository will ship FFPE blocks back to the 
external participating sites after DNA isolation is completed. Blood specimens will be processed 
locally by the external sites and stored at -80ºC until shipment. The biorepository will provide a 
shipping kit that, besides dry ice, will include all the components to pack and ship blood specimens 
in batches to the biorepository. Dry ice shipments will occur Monday to Wednesday only to allow 
for timely delivery before the weekend. 
 
7.3 
STUDY SCHEDULE 
 
7.3.1 SCREENING 
The screening visit will be conducted 0-28 days prior to Cycle 1 Day 1 (C1D1).  This visit will 
include the following procedures/assessments: 
• Informed Consent; 
• Confirm Eligibility; 
• Physical examination; 
• Height/Weight;  
• Vitals (temperature, pulse, blood pressure, respiratory rate); 
• Medical History; 

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• Baseline adverse events; 
• Concomitant medications and procedures; 
• Disease/tumor assessment;  
• ECOG performance status; 
• Hematology; 
• Serum chemistry (fasting is not required); 
• 12-lead ECG;  
CT imaging chest/abdomen/pelvis (completed 0-28 days prior to C1D1; does not have to 
be same day as screening). 
 
 
7.3.2 ENROLLMENT/BASELINE 
 
Cycle 1 Day 1  
The enrollment/baseline visit will be conducted C1D1. This visit will include the following 
procedures/assessments: 
• Confirm eligibility;  
• Hematology; 
• Lipid profile; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential/not underwent surgical menopause; 
(≤ 3 days prior to start of every cycle); 
• Physical examination; 
• Weight; 
• Vitals (temperature, pulse, blood pressure, respiratory rate); 
• Baseline adverse events; 
• Concomitant medications and procedures; 
• Genetic molecular testing (obtained by archival tissue and/or serum/plasma analysis). 
• Randomization of study medication; 
• Administration of study medication. 
7.3.3 TREATMENT   
 
Cycle 2 +, Day 1 
Study treatment will be conducted until disease progression or other reason for discontinuation.  
Cycles will be 28 days long of therapy with window of +/- 3 days for evaluation.  Study treatment 
follow-up will include the following procedures/assessments: 
• Study medication adherence and modification (as needed); 
• Administration of study medication; 
• Physical examination; 
• Weight; 
• Vitals (temperature, pulse, blood pressure, respiratory rate); 
• Concomitant medications and procedures; 

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• AE assessment; 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Disease/ tumor assessment; 
• Serum pregnancy for women of childbearing potential/not underwent surgical menopause; 
(≤ 3 days prior to start of every cycle); 
• CT imaging chest/abdomen/pelvis (to be conducted at completion of every 3rd cycle +/- 7 
days). 
 
 
7.3.4 FINAL STUDY TREATMENT VISIT 
 
End of treatment will be conducted 28 days (+14 days) following completion of treatment.  End 
of treatment will include the following procedures/assessments: 
• Discontinuation of study medication; 
• Physical examination; 
• Weight; 
• Vitals (temperature, pulse, blood pressure, respiratory rate); 
• Concomitant medications and procedures; 
• AE assessment; 
• Hematology; 
• Lipid profile; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential/not underwent surgical menopause. 
• Disease/ tumor assessment; 
• CT imaging chest/abdomen/pelvis (to be conducted at completion of study +/- 28 days 
from discontinuation of study medication). 
 
7.3.5 FOLLOW-UP 
 
For all subjects, annual follow-up visit (+/- 30 days) will be conducted via phone or medical 
records from the time of enrollment (C1D1) and will include the following assessment:  
• Survival 
 
 
7.3.6 EARLY TERMINATION  
Subjects who meet the primary endpoint (progression/recurrence/death) or severe toxicity 
requiring removal from study, an end of treatment visit will be conducted as appropriate.   
 

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7.3.7 UNSCHEDULED VISIT 
Unscheduled visits may be conducted in the event of an SAE/AE or toxic event.  The following 
assessments/procedures should be considered if appropriate: 
• Study medication adherence and modification; 
• Discontinuation of study medication; 
• Physical examination; 
• Weight; 
• Vitals (temperature, pulse, blood pressure, respiratory rate); 
• Concomitant medications and procedures; 
• AE assessment; 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential/not underwent surgical menopause;  
• CT scan chest/abdomen/pelvis; 
• Disease/ tumor assessment. 
For subjects requiring permanent termination of the study drug, subject should be discontinued 
from the study.   
 
 
7.3.8 SCHEDULE OF EVENTS TABLE 
 
 
SCHEDULE OF STUDY ASSESSMENTS 
Study Visits   
Screening 
C1D1 
Cycles 2+ 
Day 19 
End of 
Treatment 
Unscheduled 
Visit7 
Annual 
Follow-Up 
  
Day -28 to 
Day 0 
Baseline 
28 Day 
cycle (+/- 
3 days)  
28 (+14) 
days 
  
12 months 
(+/-30 
days) 
Procedures 
 
Informed consent 
X 
 
 
 
 
 
Confirm eligibility 
(Inclusion/exclusion 
criteria) 
X 
X 
 
 
 
 
Randomization 
X  
  
 
  
 
Medical History 
X 
  
  
 
  
 
Disease/Tumor 
assessment 
X 
 
X6 
X6 
 X6 
 

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Concomitant 
Medications and 
Procedures 
X 
X 
X 
X 
X 
 
Baseline AE review 
X  
X 
 
 
 
 
Adverse Events  
X 
X 
X 
 
Physical Exam1 
X 
X 
X 
X 
X 
 
ECOG performance 
status 
X 
 
 
 
 
 
Height/weight2 
X 
X 
X 
X 
X 
 
Vital signs3 
X  
X 
X 
X 
X 
 
CBC 
X 
 X 
X 
X 
X  
 
CMP 
X 
 X 
X 
X 
 X 
 
Lipid Panel 
 
X 
 
X 
 
 
Serum pregnancy4 
 
X 
X 
X 
X 
 
ECG 
X 
 
 
 
 
 
Genetic molecular 
tissue/plasma 
collection 
  
X 
 
 
 
 
Study treatment 
provided 
  
X 
X 
 
 
 
Medication adherence 
and modification 
 
  
X  
X 
X 
 
Discontinuation of 
medication 
 
 
 
X 
X 
 
CT imaging 
chest/abdomen/pelvis 
X 
  
X6 
X 
X 
 
Survival status5 
 
 
 
 
 
X8 
1 Physical exam should include at minimum cardiac, lung and abdominal exam. 
2 Height only needs to be measured at enrollment visit. 
3Temperature, pulse, blood pressure, respiratory rate.  
4 For women of childbearing potential/not underwent surgical menopause; (≤ 3 days prior to start of every 
cycle); 
 
5 Conducted by phone or medical record   
6 CT scan performed prior to enrollment, at conclusion of every 3rd cycle +/- 7 days, and at time of suspected 
recurrence (unanticipated visit) as appropriate; review of CT RECIST criteria will be conducted at screening, 
following completion of every 3rd cycle and at end of treatment.  
7 Unscheduled visit assessments/procedures should be considered if appropriate 
8 Annual follow-up from time of end of study treatment via phone call assessment of survival and AE’s until 
notification of patient death  
9 If patient has completed 24 cycles, evaluations can be completed every 3 cycles at providers discretion 
 
 
 
 
 
 
7.4 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES  
All concomitant prescription medications taken during study participation will be recorded on the 
case report forms (CRFs). For this protocol, a prescription medication is defined as a medication 

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that can be prescribed only by a properly authorized/licensed clinician. Medications reported in 
the CRF are concomitant prescription medications, over-the-counter medications, and non-
prescription medications. 
   
7.4.1 PRECAUTIONARY MEDICATIONS, TREATMENTS, AND 
PROCEDURES 
 
Effect of Other Medicinal Products or Concomitant Drugs on Rucaparib 
Enzymes responsible for rucaparib metabolism have not been identified. Based on in vitro data, 
CYP2D6, and to a lesser extent CYP1A2 and CYP3A4, were able to metabolize rucaparib. In 
population PK analysis, patients with different CYP2D6 or CYP1A2 genotypes showed 
comparable rucaparib PK. Although in vitro rucaparib metabolism mediated by CYP3A4 was 
slow, a significant contribution of CYP3A4 in vivo cannot be excluded. Caution should be used 
for concomitant use of strong CYP3A4 inhibitors or inducers. 
 
Effects of Rucaparib on Other Medicinal Products or Concomitant Drugs 
At the steady-state following treatment with 600 mg rucaparib BID, rucaparib is a moderate 
inhibitor of CYP1A2, and a weak inhibitor of CYP2C9, CYP2C19, and CYP3A. Rucaparib also 
marginally inhibits P-gp in the gut, but this is unlikely to be clinically significant. 
 
CYP1A2 Substrates 
When co-administering medicinal products metabolized by CYP1A2, particularly medicines 
which have a narrow therapeutic index (eg, tizanidine, theophylline), dose adjustments may be 
considered based on appropriate clinical monitoring. 
 
CYP2C9 Substrates 
When co-administering medicinal products that are CYP2C9 substrates with a narrow therapeutic 
index (eg, warfarin, phenytoin), dose adjustments may be considered, if clinically indicated. 
Exercise caution and consider additional International Normalised Ratio (INR) monitoring with 
co-administration of warfarin and therapeutic drug level monitoring of phenytoin, if used 
concomitantly with rucaparib. 
 
CYP2C19 Substrates 
No dose adjustment is considered necessary for co-administered medicinal products that are 
CYP2C19 substrates. 
 
CYP3A Substrates 
Caution is advised when co-administering medicinal products that are CYP3A substrates with a 
narrow therapeutic index (eg, alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, 

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ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine). Dose adjustments 
may be considered, if clinically indicated based on observed AEs. 
 
P-gp Substrates 
No dose adjustment is recommended for co-administered medicinal products that are P-gp 
substrates. 
 
Other Enzymes and Transporters 
Interaction of rucaparib with other enzymes and transporters was evaluated in vitro. Rucaparib is 
a weak inhibitor of CYP2C8, CYP2D6, and UGT1A1. Rucaparib down regulated CYP2B6 in 
human hepatocytes at clinically relevant exposures. In vitro, rucaparib is a potent inhibitor of 
MATE1 and MATE2-K, a moderate inhibitor of OCT1, and a weak inhibitor of OCT2. As 
inhibition of these transporters could increase metformin renal elimination and decrease liver 
uptake of metformin, caution is advised when metformin is co-administered with rucaparib. In 
addition, rucaparib is an inhibitor of the BCRP with an IC50 value suggesting potential BCRP 
inhibition and increased exposures of medicinal products that are BCRP substrates (eg, 
rosuvastatin). 
 
Effect of Food on Rucaparib Exposures 
A high-fat meal increased Cmax by 20% and increased AUC0-24 by 38%. The effect is not 
considered clinically significant. In clinical studies, rucaparib was administered with or without 
food. 
 
Effect of Proton Pump Inhibitors on Rucaparib Exposures 
In a population PK analysis, concomitant administration of a PPI had no clinically meaningful 
impact on rucaparib PK. 
 
 
7.5 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
There are no prohibited concomitant medications for this trial.   
 
7.6 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND 
PROCEDURES  
Subjects will be allowed to take GCSF therapies while on study.  
 
7.7     PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE  
Study drug will not be provided to the patient after their end of study participation 

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8 
ASSESSMENT OF SAFETY 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention 
in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an investigational product, 
whether or not related to the investigational medicinal product. This includes an exacerbation of 
pre-existing conditions or events, intercurrent illnesses, drug interaction, or the significant 
worsening of the indication under investigation that is not recorded elsewhere on the eCRF under 
specific efficacy assessments. Anticipated fluctuations of pre-existing conditions, including the 
disease under study, that do not represent a clinically significant exacerbation or worsening are not 
considered AEs. 
It is the responsibility of the investigator to document all AEs that occur during the study. AEs 
should be elicited by asking the patient a non-leading question (e.g., “Have you experienced any 
new or changed symptoms since we last asked/since your last visit?”). The existence of an AE may 
be concluded from a spontaneous report of the patient; from the physical examination; or from 
special tests such as the ECG, laboratory assessments, or other study-specified procedure (source 
of AE). Symptoms reported spontaneously by the patient during the physical examination would 
also qualify as an AE (and hence documented on the AE eCRF, not on the physical examination 
eCRF, which is reserved for physical signs or findings). 
 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
An SAE is any untoward medical occurrence that occurs at any dose (or, occurs after informed 
consent is given and prior to dosing if the SAE is related to a study procedure) that: 
• Results in death. Any event resulting in death during the reporting period (from date of 
first dose of study drug through 28 days after last dose) must be treated as an SAE and 
reported as such. An event related to a study procedure that occurs after informed consent, 
but prior to dosing that results in death must also be reported as an SAE. 
• Is life-threatening (patient is at immediate risk of death from the event as it occurred) 
• Requires in-patient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization 
• Results in persistent or significant disability/ incapacity 

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• Results in a congenital anomaly or birth defect 
• Important medical events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. Examples of such events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home or 
the development of drug dependency or drug abuse. 
Events or Outcomes Not Qualifying as Serious Adverse Events 
The following are not considered SAEs and therefore do not need to be reported as such: 
• Pre-planned or elective hospitalization including social and/ or convenience situations 
(e.g., respite care) 
• Hospital visits of less than 24 hours’ duration (e.g., patient presents to the emergency room, 
but is not admitted to a ward) 
• Overdose of either Clovis study drug or concomitant medication unless the event meets 
SAE criteria (e.g., hospitalization). However, the event should still be captured as a non-
serious AE on the appropriate eCRF page 
• Events of progression of the patient’s underlying cancer as well as events clearly related to 
progression of the patient’s cancer (signs and symptoms of progression) should not be 
reported as a serious adverse event unless the outcome is fatal within the safety reporting 
period. If the event has a fatal outcome within the safety reporting period, then the event 
of Progression of Disease must be recorded as an SAE with CTCAE Grade 5 (fatal 
outcome) indicated. 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse Events 
It is the responsibility of the investigator to assess the clinical significance of all abnormal values 
as defined by the list of reference ranges from the local laboratory. In some cases, significant 
changes in lab values within the normal range will require similar judgment. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an AE 
only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 
• at the discretion of the investigator should the abnormality be deemed clinically significant. 
8.1.3 ADVERSE EVENT OF SPECIAL INTEREST (AESI) 
Clovis Oncology is interested in the following adverse events of special interest (AESI): 
myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Section 6.1.9 describes 

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the appropriate follow-up and discontinuation of therapy for patients experiencing either of these 
AESIs.  
As of 27 June 2016, there have been three events of myelodysplastic syndrome (MDS) and three 
events of acute myeloid leukemia (AML) reported in patients participating in Clovis-sponsored 
clinical studies. The three events of MDS were reported in open-label studies CO-338-017 
(ARIEL2) (n = 2) and CO-338-010 (n = 1). One event of AML was reported in the open-label 
study CO-338-017, and two events of AML (one was fatal) were reported in blinded, randomized 
study CO-338-014 (ARIEL3).  
More than 1,000 patients have received oral rucaparib in Clovis-sponsored studies as 27 June 2016, 
thus these events have been observed in < 0.6% of all patients treated in these studies. Events of 
MDS and AML have also been reported with another PARPi [23]. All patients experiencing these 
events received prior treatment with chemotherapy. While the etiology of these events is 
confounded by prior treatments and the relationship to rucaparib is not clear, Clovis has added 
these potential risks to all Informed Consent Forms (ICFs) / Patient Information Sheets (PISs). 
Adverse events of special interest (AESIs) (both serious and non-serious) will be reported to Clovis 
within 48 business hours of awareness and will continue to be reported to Clovis. 
8.1.4 DEFINITION OF UNANTICIPATED PROBLEMS (UAP) 
The Office of Human Research Protection (OHRP) considers unanticipated problems involving 
risks to participants or others to include, in general, any incident, experience, or outcome that 
meets all of the following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the participant 
population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research); and 
• Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
This study will use the OHRP definition of UAP. 

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8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
The investigator has the responsibility for assessing the safety of the patients and for compliance 
with the protocol to ensure study integrity. Patients will be monitored for AEs during study 
participation (beginning at the time informed consent is obtained) and until 28 days after the last 
dose of study drug. After the 28-day window, only treatment-related SAEs and all AESIs, 
irrespective of causality, need to be reported. In the time after informed consent is provided but 
before study drug is administered, AEs/ SAEs are to be recorded if they are the result of a study-
related procedure. Any ongoing SAEs, AESIs, or treatment-related Grade 3/4 AEs will be followed 
until resolution or stabilization. AEs and laboratory abnormalities will be graded according to the 
NCI CTCAE grading system (Version 4.03) and recorded on the eCRF. 
 
8.2.1 SEVERITY OF EVENT 
The severity of each AE will be graded using the NCI CTCAE, Version 4.03 grading scale [24]. 
For AEs not included in the protocol-defined grading system, the following guidelines will be used 
to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating. 
• Life-threatening – Life-threatening events require urgent intervention to prevent death 
• Fatal – Death 
  
8.2.2 RELATIONSHIP TO STUDY AGENT 
The clinician’s assessment of an AE’s relationship to study agent (drug, biologic, device) is part 
of the documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. All AEs must have their relationship to the study agent assessed. In a clinical trial, the 
study product must always be suspect. To help assess, the following guidelines are used.  
• Related – The AE is known to occur with the study agent, there is a reasonable 
possibility that the study agent caused the AE, or there is a temporal relationship 
between the study agent and event. Reasonable possibility means that there is evidence 
to suggest a causal relationship between the study agent and the AE. 

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• Not Related – There is not a reasonable possibility that the administration of the study 
agent caused the event, there is no temporal relationship between the study agent and 
event onset, or an alternate etiology has been established. 
Not Related 
To Study Drug 
• An AE that is clearly due to extraneous causes (e.g., concurrent 
disease, concomitant medications, disease under study, etc.) 
• It does not follow a reasonable temporal sequence from administration 
of the study drug. 
• It does not follow a known pattern of response to study drug 
• It does not reappear or worsen when study drug is restarted. 
• An alternative explanation is likely, but not clearly identifiable. 
Related to 
Study Drug 
• An AE that is difficult to assign to alternative causes. 
• It follows a strong or reasonable temporal sequence from 
administration of study drug. 
• It could not be reasonably explained by the patient’s clinical state, 
concurrent disease, or other concomitant therapy administered to the 
patient.  
• It follows a known response pattern to study drug 
• It is confirmed with a positive rechallenge or supporting laboratory 
data. 
 
Outcome and Action Taken 
The investigator will record the action taken and outcome for each AE according to the following 
criteria: 
Action Taken with Study Drug (note all that apply) 
• None 
• Dose reduced/delayed 
• Study drug temporarily interrupted 
• Study drug permanently discontinued 
• Other (specify) 
 
Outcome 
• Recovered 
• Recovered with sequelae 
• Recovering/ Resolving/ Improving 
• Ongoing 
• Death 
• Lost to follow-up 
 
8.2.3 EXPECTED ADVERSE EVENTS  

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The Investigator will be responsible for determining whether an AE is expected or unexpected. An 
AE will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the reference safety information of the investigator brochure previously described for the 
study agent. 
 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study participant presenting for medical care, or upon review by a study 
monitor. All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate CRF. Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with 
the training and authority to make a diagnosis), and time of resolution/ stabilization of the event. 
All AEs occurring while on study must be documented appropriately regardless of relationship. 
All AEs will be followed to adequate resolution. 
Any medical condition that is present at the time that the participant is screened will be considered 
as baseline and not reported as an AE. However, if the study participant’s condition deteriorates 
at any time during the study, it will be recorded as an AE. UAPs will be recorded in the data 
collection system throughout the study. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The PI will record all reportable events with start dates occurring any time after informed consent 
is obtained until 7 (for non-serious AEs) or 28 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of AE/ SAEs 
since the last visit. Events will be followed for outcome information until resolution or 
stabilization. 
All AEs (including SAEs and AESIs) occurring during the study are to be followed up in 
accordance with good medical practice until resolved; judged no longer clinically significant; or, 
if a chronic condition, until fully characterized through 28 days after the last dose of study drug. 
Any SAEs, AESIs, and treatment-related Grade 3/4 AEs must be followed until resolution or 
stabilization, or until lost to follow-up. After the 28-day window, treatment-related SAEs and all 
AESIs, irrespective of causality, need to be reported.  

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8.4 
REPORTING PROCEDURES 
8.4.1 ADVERSE EVENT REPORTING  
Events that occur after signing of informed consent but prior to initiation of study drug, unless due 
to a protocol-mandated procedure, should be recorded on the Medical History eCRF. Any AE that 
occurs after first dose of study drug through 28 days after receiving the last dose of study drug will 
be recorded on the AE eCRF. 
In order to avoid vague, ambiguous, or colloquial expressions, the AE should be recorded in 
standard medical terminology rather than the patient’s own words. Whenever possible, the 
investigator should combine signs and symptoms that constitute a single disease entity or 
syndrome into a final diagnosis, if appropriate. For example, fever, cough, and shortness of breath 
may be reported as pneumonia, if that is a reasonable diagnosis. 
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the 
investigational drug. The action taken and the outcome must also be recorded. 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
SAEs and AESIs that occur during the study or within 28 days after receiving the last dose of study 
drug, whether or not related to study drug, must be reported to Clovis immediately (i.e., within 48 
hours or 2 calendar days from knowledge of the event) to the Sponsor/ SAE designee. Secondary 
sites will report SAEs and AESIs to the coordinating site for report to the sponsor.  The contact 
information for reporting of SAEs/ AESIs can be found on the SAE/ AESI Reporting Form. After 
the 28-day reporting window after discontinuation of randomized treatment only SAEs assessed 
as related to study drug and all AESIs, irrespective of causality, need to be reported. Information 
on the follow-up of AEs, SAEs, and AESIs is provided below. 
Clovis or the Sponsor-Investigator’s study-specific Serious Adverse Event (SAE)/Adverse Events 
of Special Interest (AESI) Report Form must be used for reporting SAEs and AESIs. The contact 
information for reporting of SAEs and AESIs can be found on the SAE/AESI Reporting Form and 
Pregnancy Report Forms. 
The study clinician will complete an SAE Form within the following timelines: 
• All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the SAE Form and submitted to the study sponsor within 24 hours of site 
awareness. See Study Contact Listing for contact information. 
• Other SAEs, regardless of relationship, will be submitted to the study sponsor within 5 
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All SAEs will be followed until satisfactory resolution or until the site PI deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be 
requested by the study sponsor and should be provided as soon as possible.  
The study sponsor will be responsible for notifying FDA of any unexpected fatal or life-threatening 
suspected adverse reaction as soon as possible but in no case later than 7 calendar days after the 
sponsor’s initial receipt of the information. 
8.4.3 UNANTICIPATED PROBLEM REPORTING  
 
Incidents or events that meet the OHRP criteria for UAPs require the creation and completion of 
a UAP report form. It is the site PI’s responsibility to report UAPs to their IRB, using the IRB’s 
standard UAP form. The Lead PI is responsible for reporting the UAP to the UCCC DSMC, if 
applicable. If an IRB UAP form is not provided, the UAP report will include the following 
information: 
• Protocol-identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• A detailed description of the event, incident, experience, or outcome; 
• An explanation of the basis for determining that the event, incident, experience, or 
outcome represents a UAP; 
• A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UAP. 
To satisfy the requirement for prompt reporting, UAPs will be reported using the following 
timeline: 
• UAPs that are SAEs will be reported to the IRB and study sponsor within five (5) days 
of the investigator becoming aware of the event. 
• Any other UAP will be reported to the IRB and study sponsor at annual review.  
 
8.4.4 REPORTING OF PREGNANCY 
Based on the finding that rucaparib was embryotoxic at all doses administered in the embryofetal 
development study and the potential of PARP inhibitors to affect spermatogenesis (See IB, Section 
6.2.2), it is advised that patients of reproductive potential and their opposite sex partners of 
reproductive potential practice a highly effective method of contraception during and after 
treatment with rucaparib as specified per protocol. Specifically, female patients of childbearing 
potential and their male partners are advised to practice a highly effective method of contraception 
during treatment with rucaparib and for 6 months following the last dose of rucaparib.  
A woman is considered to be of childbearing potential unless one of the following applies: 
• Is considered to be permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 

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• Is postmenopausal, defined as no menses for 12 months without an alternative medical 
cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal 
range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women 
not using hormonal contraception or hormonal replacement therapy; however, in the 
absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm 
a postmenopausal state. 
Highly effective contraception is considered to be a method with a < 1% per year failure rate. 
Recommendations for highly effective contraception while taking rucaparib include: 
• Ongoing use of injectable or implantable progesterone 
• Placement of an intrauterine device or intrauterine system 
• Bilateral tubal occlusion 
• Complete (as opposed to periodic) abstinence 
• Male sterilization, with appropriate post-vasectomy documentation of absence of sperm in 
ejaculate 
In addition, monthly serum pregnancy testing is recommended for women of childbearing potential 
taking rucaparib. Treatment should be discontinued immediately in any woman found to have a 
positive pregnancy test while taking rucaparib. 
Pregnancies should be reported to the sponsor using the pregnancy report form  
If a patient becomes pregnant during the study the investigator is to stop dosing with study drug(s) 
immediately. 
A pregnancy is not considered to be an AE or SAE; however, any pregnancy occurring in a study 
patient or partner of a study patient during study participation or within 6 months of last dosing 
must be reported to the sponsor using the Pregnancy Report Form within the same timelines as an 
SAE. 
A pregnancy should be followed through to outcome, whenever possible. Once the outcome of the 
pregnancy is known, the Pregnancy Outcome Report Form should be completed and reported to 
the Sponsor. 
AEs, SAEs, or AESIs that occur during pregnancy will be assessed and processed according to the 
AE or SAE/AESI processes using the appropriate AE or SAE/AESI forms. 
8.5 
SAFETY OVERSIGHT 
Medical Monitoring 
Medical monitoring and monitoring of SAEs across all sites will be monitored by Dr. Bradley Corr 
on a continuous basis. All SAEs must be reported to Dr. Corr at the University of Colorado within 

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48 hours of event.  The sponsoring site will be responsible for reporting such events to the 
overseeing IRB and the sponsor within 5 days of event.   
Data Safety Monitoring Plan 
The Principal Investigator (PI) will be responsible for monitoring the trial per the trial monitoring 
plan, in addition to overseeing the safety and efficacy of the trial, executing the DSM plan, and 
complying with all reporting requirements to local and federal authorities. This oversight will be 
accomplished through additional oversight from the Data and Safety Monitoring Committee 
(DSMC) at the University of Colorado Cancer Center (CU Cancer Center).  The DSMC is 
responsible for ensuring data quality and patient safety for all clinical studies at the CU Cancer 
Center.   A summary of the DSMC’s activities is as follows: 
• Conduct of internal audits 
• Ongoing review of all serious adverse events (SAEs), unanticipated problems (UAPs) and 
reportable adverse events (AEs)  
• Has the authority to close and/or suspend trials for safety or trial conduct issues 
• May submit recommendations for corrective actions to the CU Cancer Center’s Executive 
Committee 
Per the CU Cancer Center Institutional DSM Plan, SAEs, UAPs and reportable AEs are reported 
to the DSMC, IRB and the sponsor per study protocol.  All SAEs, UAPs and reportable AEs are 
to be reported to the DSMC within 5 business days of receiving notification of the occurrence. 
Each subject’s treatment outcomes will be discussed by the Investigators and Clinical Research 
Coordinators (CRCs) at regularly scheduled disease-oriented working group meetings.  Data 
regarding number of subjects, significant toxicities, dose modifications, and treatment responses 
will be discussed and documented in the meeting’s minutes. 
The PI will provide a DSM report to the CU Cancer Center DSMC on a six-month basis. The DSM 
report will include a protocol summary; current enrollment numbers; summary of toxicity data to 
include specific SAEs, UAPs and AEs; any dose modifications; all protocol deviations; and 
protocol amendments. The DSM report to the DSMC will also include, if applicable, the results of 
any efficacy data analysis conducted, as well as any internal DSMB reports. Results and 
recommendations from the review of this six-month report by the DSMC will then need to be 
submitted by the site to the IRB of record at the time of continuing review. 
The coordinating site (UCD) is responsible for organizing and conducting monthly teleconferences 
with all participating sites.  The PI will also be responsible for including data from all of the 
participating sites within the overall trial’s six month DSM report to the DSMC to include minutes 
from monthly PI teleconferences.  The Clinical Trials Office at UCD will provide monitoring of 

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the coordinating site.  The data manger will provide additional internal data validation for the 
coordinating site and monitoring for all additional participating sires.  Each participating site will 
be responsible for submitting the results and recommendations from the DSMC’s six-month 
review to their IRB of record at the time of continuing review. 
9 
CLINICAL MONITORING 
Clinical site monitoring will be conducted to ensure that the rights and well-being of human 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/ amendment(s), 
with GCP, and with applicable regulatory requirement(s).  
Clinical monitoring of the study will be conducted by research personnel (data manager) from the 
University of Colorado Denver for all additional sites. The University of Colorado will conduct 
their own audit and validation of study entry with internal research personnel through the Clinical 
Trials office.  In order to conduct monitoring, study sites should make staff and resources available 
for the following: 
• Initial in-service of the study site, including investigator training and site tour 
• Regular attendance of progress meetings 
• Research staff available for interim monitoring visits 
• All study documents (consents, CRFs, etc.…) available for site visits in which the monitor 
will verify accuracy of data as entered into the electronic database 
• Response to data requests via fax/email if site visit is not necessitated 
• Maintenance of all regulatory documents and accessible for monitor review (UCD may 
request these be sent to the lead site for regulatory maintenance) 
• Research staff available to response to data queries and resolve inconsistencies in study 
records 
• Close out of the study at the study site 
The study monitor will provide each site with a report of the monitor visit to be submitted to their 
local IRB.  In addition to monitoring visits, a monthly conference call will take place among all 
sites to discuss treatment outcomes, enrollment, significant toxicities, dose modifications and 
responses. These meetings will be documents and the minutes shared with all sites.  
Additionally, the University of Colorado Cancer Center DSMC will conduct independent audits 
of study sites to evaluate conduct and compliance of the investigational protocol as a study site.  
All study documents and regulatory documents must be available to audit.  The audit reviewer will 
also require direct access to study source (participant medical records relating to study) and time 
with the site investigator and/or regulatory personnel during their visit. 

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10 
STATISTICAL CONSIDERATIONS  
10.1 STATISTICAL AND ANALYTICAL PLANS 
A modified intent-to-treat analysis will be based on participants initiating assigned medication for 
first day of treatment.  All participants randomized who receive the assigned study medication at 
least once will be included for analysis.   
Data will be abstracted regarding participant demographics, disease status, adverse/toxicity, and 
clinical endpoints (progression and survival).  This is a comparative study designed to assess the 
efficacy with use of maintenance Rucaparib for women with recurrent and/or metastatic 
endometrial cancer compared to placebo.  Secondary endpoints will assess the efficacy for overall 
survival, specific genetic markers, and toxicity.  
Treatment will be taken for 28 consecutive day cycles until progression of disease or death with 
follow-up continuing for 24 months after discontinuation of study treatment.  Progression free 
survival (in months) will be compared between the treatment arm A (Rucaparib 600mg BID) and 
arm B (placebo control).  Biostatisticians will remain blinded to the treatment arm assignments 
during analysis.   
Participants will be analyzed employing a modified intention-to-treat approach (analyzed based 
on receiving assigned study medication at least once).   Participants will not be allowed to change 
treatment arms while on trial.  
10.2 STATISTICAL HYPOTHESES 
• Primary Efficacy Endpoint(s): 
We hypothesize that the use of PARP inhibitor maintenance therapy will improve PFS by 
a median of 4 months compared to placebo in patients with recurrent or metastatic 
endometrial cancer who have completed standard first line chemotherapy. 
 
• Secondary Efficacy Endpoint(s): 
We hypothesize that the use of PARP inhibitor maintenance therapy will improve OS 
compared to placebo in patients with recurrent or metastatic endometrial cancer who have 
completed standard first line chemotherapy. 

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10.4 DESCRIPTION OF STATISTICAL METHODS 
10.4.1 GENERAL APPROACH  
 
Descriptive statistics using means, frequencies, and percentages will be computed to describe the 
study population.  Participant data will be analyzed employing the intention-to-treat approach.    
Student’s t-tests (for continuous variables) and chi-square tests (for categorical variables) will be 
used to compare the two groups for demographic and secondary outcome variables. A p-value of 
<0.05 will be used to demonstrate statistical significance for secondary outcomes. For the primary 
outcome measure, progression free survival, and the secondary outcome, overall survival, Kaplan-
Meier curves will be displayed and the log-rank test will be used to compare the curves between 
the two arms. Cox regression model will be used to identify significant predictors associated with 
the primary outcome. The log-rank test and Cox model will be stratified based on the 
randomization strata.  IBM SPSS version 24, SAS, or R will be used for all statistical analyses.   
 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
The primary objective of this study is to test efficacy in progression free survival (PFS) in Arm 
A when compared to Arm B.  Progression free survival will be determined from start of study 
treatment till time of progression as detected by CT exam and determined by RECIST 1.1 criteria. 
Kaplan-Meier curves will be displayed and log-rank test will be used to compare the curves 
between the two arms.  Cox proportional hazard model will be used to determine hazard ratio.  A 
one sided hypothesis test with an alpha of 0.10 will be used to assess whether a significant 
difference exists between the treatment arms.  
 
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Overall survival (OS) will be compared between the treatment groups.  OS will be tested using 
log-rank test in the same manner as for the primary endpoint. A one sided hypothesis test with an 
alpha of 0.10 will be used to assess whether a significant difference exists between the treatment 
arms. 
 
10.4.4 SAFETY ANALYSES 
Safety evaluation will include incidence and severity of adverse events and significant laboratory 
abnormalities.  Safety analysis will be performed on all patients who received at least one dose of 
the treatment drug.   Safety and tolerability will be tabulated by system organ class and preferred 
term. Tables of serious adverse events, treatment-related AEs, and adverse events leading to 
withdrawal from investigation product will also be provided. Summary statistic will be provided 
for total number of doses, average dose administered, and duration of treatment.  

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For select laboratory parameters, changes of laboratory values over time (e.g., change from 
baseline summary statistics), grade shifts in laboratory values from baseline to worst on-study 
value, and grade 3 or higher laboratory toxicities will be summarized.  
Incidence of AEs and SAEs will be compared between treatment arms using chi-square analysis.  
A p-value of <0.05 will be used to demonstrate statistical significance.   
10.4.5 ADHERENCE AND RETENTION ANALYSES 
Adherence and retention of study therapy be described by treatment delays and early terminations 
due to therapy toxicities.    
 
10.4.6 BASELINE DESCRIPTIVE STATISTICS 
Descriptive statistics using means, frequencies, and percentages will be computed to describe the 
study population.  Participant data will be analyzed employing the intention-to-treat approach.    
Student’s t-tests (for continuous variables) and chi-square tests (for categorical variables) will be 
used to compare the two groups for demographic and secondary outcome variables.  
 
10.4.7 EXPLORATORY ANALYSES 
Disease response for molecular measures (BRCA, HRD, PTEN, PIK3CA, AKT) 
To evaluate the association between disease response (measured in a binary manner as 
“responded” or “did not respond”) and several molecular measures (BRCA, HRD, PTEN, 
PIK3CA, AKT).  Associations of response with categorical measures will be tested using 
Pearson’s chi-square test, each test controlling the type 1 error rate at 0.05. 
 
10.5 SAMPLE SIZE 
Using a median PFS of 8 months based on GOG 177 data and an expected improvement of 4 
months median PFS to 12 months, we estimate we will need a sample size of 123 patients total to 
determine significance with a hazard ratio of 0.67. This sample size was estimated using a one-
sided alpha of 0.1 and a power of 0.8. In addition, an accrual time of 23 months (explained below) 
and a total study period of 48 months was assumed.  We will add an additional 12% of patients for 
withdrawals for a total sample size of 138 (69 per arm). 
 
This study will be conducted over 48 months.  This allows for ~23 months of accrual, followed by 
24 months of follow-up to complete the study.  The University of Colorado sees on average 5 cases 
of recurrent endometrial cancer/month.  Assuming that half of the patients approached will meet 
eligibility and consent to participate, we can estimate 2.5 subjects enrolled per month at the 
coordinating site.  We anticipate similar recruitment/enrollment goals from the secondary sites.  
The secondary sites will accrue for approximately 16 months with an additional 24 months of 

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follow-up.  The lag of time accounts for the sub-contract and study site approval process at the 
secondary site.  With UCD accruing for 23 months and the secondary sites accruing for 16 months 
each all at a rate of 2.5 subjects per month, we can meet our enrollment goals at 23 months.  Again, 
all sites will have a 24-month follow-up time bring the total study duration to 4 years, or 48 months 
total.   
 
10.6 MEASURES TO MINIMIZE BIAS 
We will use the following methods to minimize bias for this trial:  
• Participation bias: We will employ a double-blinding by participants and study 
investigators.   
• Selection bias: Participants will be randomized 1:1 to treatment arms.  
• Confounding: the following variables will be stratified between treatment arms to minimize 
any potential confounding: tumor histology.  Additional variables will be considered for 
stratification in the analysis to determine if confounding exists (prior # of therapies, 
response to previous therapy).  
 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
 
Participants will be randomized on C1D1 after confirmation of eligibility and consent. The 
Biostatistician at UCD will provide the randomization schema to each study site.  Medication will 
be blinded by the drug sponsor, Clovis, prior to arriving to the clinical research site. Study sites 
will receive the blinded medication directly from the study sponsor and will be stored at the study 
sites’ investigational pharmacy. Medication will be prescribed as either treatment A or treatment 
B and masked in two identical bottles.  The participant will continue to receive the same treatment 
type for the remainder of the study.  Research personnel will verify the treatment drug provided at 
the start of each study cycle.  
 
10.6.2 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
 
In the event of a life-threatening medical necessity, death, or provider request for treatment 
consideration, the PI may request the unblinding of a study participant.  The PI will contact the 
drug sponsor, Clovis Oncology, to break the blind in order to report to the required local and 
federal agencies as requested.  
 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
FDA law and regulations require the collection and maintenance of complete clinical study data. 
This includes information on subjects who withdraw from a clinical investigation, whether the 

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subject decides to discontinue participation in the clinical trial (21 CFR 50.25(a)) or is discontinued 
by the investigator because the subject no longer qualifies under the protocol (for example, due to 
a significant adverse event or due to failure to cooperate with study requirements). FDA recognizes 
that a subject may withdraw from a study; however, the withdrawal does not extend to the data 
already obtained during the time the subject was enrolled. FDA’s longstanding policy has been 
that all data collected up to the point of withdrawal must be maintained in the database and 
included in subsequent analyses, as appropriate. 
All study documentation should remain on study site in a secured area with limited access. 
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by Clovis, whichever is longer.  
If the investigator withdraws from the study (e.g., relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (e.g., another investigator, IRB). Notice of such 
transfer will be given in writing to Clovis.  
11.1 RESEARCH ELECTRONIC DATA CAPTURE 
All study data should be entered in the electronic data capture.  For this study the electronic data 
capture will be supported by REDCap.  Prior to the start of trial, site investigators and research 
staff must complete REDCap in-service provided by the University of Colorado Denver.  The 
study site will maintain documentation of REDCap training for each person approved for accessing 
REDCap.  Access will then be granted by the University of Colorado.  Site personnel with REDCap 
access will be able to maintain study records with review and edit permission. 
 
11.2 DATA MANAGEMENT 
All data entered into the REDCap database will be maintained by the host site for the REDCap 
database, the University of Colorado Denver.  The University of Colorado research staff will 
review the database for completion of data and data inconsistencies and request resolution by the 
appropriate site.  The University of Colorado will be responsible for all export and analysis of 
study data.  Any requests for data sharing will be considered after completion of study analysis. 
 
11.3 CONFIDENTIALITY AND REPORTING OF RESULTS 
The information on individual subjects arising from this study is to be considered confidential and 
transmitted to the sponsor only in a form that will not permit identification of the individual. The 
information obtained from the subjects that can be identified with the subject will remain 
confidential within the research team. Research teams will maintain all records in a secure area 

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with limited access. Regulatory and sponsoring agencies may request access to the study records 
and related medical records of each participating subject.  If requested, the subject’s identity will 
remain confidential to the extent permitted by the applicable laws and regulations. The results of 
the research will be released to public agencies including regulatory agencies, clinical 
investigators, and research organizations without reference to items identifiable to a particular 
subject. The results will be published such that the identity of the subjects will not be disclosed 
and cannot be ascertained. 
 
11.4 RETENTION OF DATA 
The clinical research records must be retained for a minimum of two years after the marketing 
application is approved for the drug for the indication for which it was being investigated. 
Alternatively, if no application will be filed or if the application is not approved for the requested 
indication, the records must be retained for a minimum of two years after the investigation is 
discontinued and FDA is notified. 21 CFR §312.62(c) 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
Quality Control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/ resolution. 
Following written SOPs, the study monitor will verify that the clinical trial is conducted and data 
are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the 
applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing 
Practices (GMP)). 
The investigational site will provide direct access to all trial-related sites, source data/ documents, 
and reports for the purpose of monitoring and auditing by the DSMC audit team, and inspection 
by local and regulatory authorities. 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
13.1 ETHICAL STANDARD  
The PI will ensure that this study is conducted in full conformity with regulations for the Protection 
of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56. ICH 
E6 may also be followed to the extent it has been adopted by and is in accordance with FDA 
regulations. 
 

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13.2 INSTITUTIONAL REVIEW BOARD  
The protocol, informed consent forms), recruitment materials, and all subject materials will be 
submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the 
protocol and the consent form must be obtained before any subject is enrolled. Any amendment to 
the protocol will require review and approval by IRB before the changes are implemented to the 
study. All changes to the consent form will IRB approved; a determination will be made regarding 
whether previously consented participants need to be re-consented. 
 
13.3 INFORMED CONSENT PROCESS  
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS 
PROVIDED TO PARTICIPANTS 
 
Consent forms describing in detail the study agent, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/ administering study product.  
 
13.3.2  CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent process will be initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks 
and possible benefits of participation will be provided to the participants and their families.  
Consent forms will be IRB-approved and the participant will be asked to read and review the 
document. The investigator will explain the research study to the participant and answer any 
questions that may arise. All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants will have the opportunity to discuss the 
study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign the informed consent document prior to any procedures being done specifically for the study.  
The participants may withdraw consent at any time throughout the course of the trial. A copy of 
the informed consent document will be given to the participants for their records. The rights and 
welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
The study allows the inclusion of non-English speaking and non-reading participants. Witnesses 
to these consent processes will be individuals not associated with the trial and will not have a 
conflict of interest. 

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13.4 PARTICIPANT AND DATA CONFIDENTIALITY  
Participant confidentiality is strictly held in trust by the participating PIs, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples 
and genetic tests in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. 
No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records (office, clinic, 
or hospital) and pharmacy records for the participants in this study. The clinical study site will 
permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by local IRB and Institutional regulations. 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at the University of Colorado Cancer Center. This will not include 
the participant’s contact or identifying information. Rather, individual participants and their 
research data will be identified by a unique study identification number. The study data entry and 
study management systems used by clinical sites and by the University of Colorado Denver 
research staff will be secured and password protected. At the end of the study, all study databases 
will be de-identified and archived at the University of Colorado Denver. 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES, SPECIMENS OR 
DATA 
 
Stored human samples will include archived tumor and genomic DNA samples.  Archived tumor 
and germ line DNA samples will be used for genomic testing.  Genetic testing data will be used in 
the exploratory analysis examining tumor genetics and disease response.   
 
13.5 FUTURE USE OF STORED SPECIMENS  
Biospecimens for this study will be stored at the University of Colorado Biorepository Core 
Facility. If there are remaining specimens after research is concluded for this study, specimens will 
be banked for additional future research at the University of Colorado Biorepository Core Facility. 
Participants will provide informed consent for this long-term storage and future research use. 
During the conduct of the study, an individual participant can withdraw consent to have 
biospecimens stored for future research. However, withdrawal of consent with regard to 

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biospecimen storage will not be possible after the study is completed. Specimens for future 
research will be provided in a deidentified manner and will be stripped of any patient and/or study 
identifiers. 
 
14 
DATA HANDLING AND RECORD KEEPING  
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. The PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness of 
the data reported.  
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. When making changes or corrections, cross out the original entry with a 
single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR USE 
CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained 
for recording data for each participant enrolled in the study. Data reported in the eCRF derived 
from source documents should be consistent with the source documents or the discrepancies should 
be explained and captured in a progress note and maintained in the participant’s official electronic 
study record. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into REDCap, am encrypted, web-based data capture 
system provided by the University of Colorado Clinical and Translational Sciences Institute [25]. 
The data system includes password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be 
entered directly from the source documents.  
14.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 2 years after the last approval of an 
investigational marketing application and until there are no pending or contemplated marketing 
applications or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents should be retained for a longer 
period, however, if required by local regulations, or institution policies. No records will be 
destroyed without the written consent of the sponsor, if applicable.  
 

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14.3 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or SOP 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. These practices are consistent with ICH E6, sections: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3. 
• 5.1 Quality Assurance and Quality Control, section 5.1.1. 
• 5.20 Noncompliance, sections 5.20.1 and 5.20.2. 
 
All deviations must be addressed in study source documents, reported to the local IRB, 
coordinating site/sponsor and DSMB.  Protocol deviations must be sent to the local IRB per their 
guidelines. The site PI/ study staff is responsible for knowing and adhering to their IRB 
requirements. Further details about the handling of protocol deviations will be included in the -
SOP and/or study procedures manual.  
 
15 
STUDY ADMINISTRATION 
15.1 
STUDY LEADERSHIP 
This study will be led by the principal investigator Bradley R. Corr, MD from the University of 
Colorado Denver; Aurora, CO 80045.  Any questions in regards to the study leadership and 
oversight should be directed to them.  
 
16 
CONFLICT OF INTEREST POLICY 
Independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed by the 
University of Colorado Denver’s (UCD) Office of Regulatory Compliance Conflict of Interest and 
Commitment Management (COIC) program. Persons with a perceived conflict of interest will have 
such conflicts managed in a way that is appropriate to their participation in the trial. Conflict of 
Interest management plans are project-specific and are reviewed at least annually. UCD has 
integrated the institutional conflict of interest management program with its existing program. 
 

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17  
LITERATURE REFERENCES  
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PARP inhibitors. Sci Transl Med, 2010. 2(53): p. 53ra75. 
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Forster, M.D., et al., Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial 
cancer. Nat Rev Clin Oncol, 2011. 8(5): p. 302-6. 
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Ossovskaya, V., et al., Upregulation of Poly (ADP-Ribose) Polymerase-1 (PARP1) in Triple-Negative Breast 
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125(3): p. 771-771. 
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Audeh, M.W., et al., Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 
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Gelmon, K.A., et al., Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian 
carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. 
Lancet Oncol, 2011. 12(9): p. 852-61. 
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Ledermann, J., et al., Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous 
ovarian cancer (SOC) and a BRCA mutation (BRCAm). Journal of Clinical Oncology, 2013. 31(15_suppl): p. 
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Mateo, J., et al., DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med, 2015. 
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Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised RECIST guideline 
(version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 

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22. 
Lolas Hamameh, S., et al., Genomic analysis of inherited breast cancer among Palestinian women: Genetic 
heterogeneity and a founder mutation in TP53. Int J Cancer, 2017. 141(4): p. 750-756. 
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Kim, G., et al., FDA Approval Summary: Olaparib Monotherapy in Patients with Deleterious Germline 
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Institute, N.C., Common Terminology Criteria for Adverse Events, Version 4.03Common Terminology 
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p. 377-81. 
 
18  
APPENDICES  
Version 
Date 
Significant Revisions