Clinical trial NCT01540565
Conditions: BRCA1 Mutation Carrier BRCA2 Mutation Carrier Ovarian Epithelial Tumor Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma
Sponsor: National Cancer Institute (NCI)
Start date: 2012-04-09; Completion date: 2018-01-27
Enrollment: 52 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well veliparib works in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who have objective tumor response (complete or partial).

II. To determine the frequency and severity of adverse events associated with treatment with veliparib (ABT-888) as assessed by the Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the proportion of patients who survive progression-free for at least 6 months.

TERTIARY OBJECTIVES:

I. To explore the association between single nucleotide polymorphisms (SNPs) in deoxyribonucleic acid (DNA) repair genes (e.g., breast cancer \[BRCA\]1, Fanconi) and clinical characteristics, response, and patient outcome (PFS and OS).

OUTLINE:

Patients receive veliparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Arms: arm 1: Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Laboratory Biomarker Analysis intervention 2: Veliparib
Intervention descriptions: intervention 1: Correlative studies intervention 2: Given PO

Protocol documents:
Prot_SAP_000.pdf: 
Philip J. DiSaia, M.D. 
President 
 
Administrative Office 
Four Penn Center 
1600 John F. Kennedy Boulevard, Suite 1020 
Philadelphia, Pennsylvania 19103 
Phone: 215-854-0770 Fax: 215-854-0716 
 
Laura L. Reese 
Executive Director of Operations 
 
Larry J. Copeland, M.D. 
Vice President  
 
Finance/Development Office 
2127 Espey Court 
Suite 100 
Crofton, Maryland 21114 
Phone: 410-721-7126 Fax: 301-261-3972 
 
Mary C. Sharp 
Chief Financial Officer 
 
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SUMMARY OF CHANGES 
 
For Protocol Amendment #5 to: 
 
NCI Protocol #: GOG-0280 
Local Protocol #: GOG-0280 
 
NCI Version Date: 05/02/2016 
Protocol Date:  
 
This amendment is being submitted in response to an RA from Dr. Richard Piekarz (piekarzr@mail.nih.gov). 
 
 
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The PMB Phone number has been updated to 240-276-6575. 
3. 
4.112 
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CAEPR has been updated and is now Version 2.3, March 4,2016. 
•   The SPEER grades have been updated. 
 
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Appendix II has been updated to the current version; the last bullet has been 
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IC 
 
Additional changes have been made to the Informed Consent. 
 


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PROTOCOL GOG-0280 
A PHASE II EVALUATION OF THE POLY (ADP-RIBOSE) POLYMERASE (PARP) -1 AND -2 INHIBITOR 
VELIPARIB (ABT-888) (IND #77840) (NSC #737664) IN THE TREATMENT OF PERSISTENT OR 
RECURRENT EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER 
PATIENTS WHO CARRY A GERMLINE BRCA1 OR BRCA2 MUTATION (07/09/2012) 
NCI Version Date: 05/02/2016 
Includes Revisions #1 -5 
POINTS: 
PER CAPITA – 20 (07/09/2012) 
MEMBERSHIP - 6
TR PER CAPITA – Award based on specimen submission with 1.0 point for pre-treatment FFPE (FR01 
or FP01/FM01), frozen (RR01 or RP01/RM01), serum (SB01), whole blood (WB01), and post-treatment 
specimen (FR02 or PF01) (MAX TOTAL = 5.0). 
PARTICIPATION OPEN GROUP-WIDE, CURRENTLY Pharmaceutical Management 
Branch/Industry Sponsor CAN SHIP ONLY TO US sites 
Lead Organization: NRG/NRG Oncology 
STUDY CHAIR 
STUDY CO-CHAIR 
ROBERT L. COLEMAN, M.D. 
CAROL AGHAJANIAN, M.D. 
UT M.D. ANDERSON CANCER CENTER 
See GOG Website Directory 
DEPARTMENT OF GYN ONCOLOGY-UNIT 1362 
 
PO BOX 301439 
NURSE CONTACT 
HOUSTON, TX 77230-1439 
MARIA S. JUNG, R.N. 
713-745-3357 
M.D. ANDERSON CANCER CENTER 
FAX: 713-792-7586 
DEPARTMENT OF GYN ONCOLOGY, UNIT 440 
E-MAIL: rcoleman@mdanderson.org    
1515 HOLCOMBE BLVD. 
 
HOUSTON, TX 77030-4009 
STATISTICIAN 
713-745-3897 
MICHAEL SILL, PH.D. 
FAX: 713-745-4480 
See GOG Website Directory 
E-MAIL: mjung@mdanderson.org  
 
 
TRANSLATIONAL RESEARCH CO-CHAIR 
TRANSLATIONAL RESEARCH SCIENTIST 
MICHAEL J BIRRER, MD, PhD 
HEATHER A. LANKES, PH.D., M.P.H. 
See GOG Website Directory 
See GOG Website Directory 
 
 
SCIENTIFIC COLLABORATOR 
 
ELIZABETH SWISHER, MD 
 
See GOG Website Directory 
 
 
 
 
 
 
 
 
SCHEMA 
Veliparib 400 mg oral twice daily 
Until disease progression or adverse effects prohibit further therapy 
 
One cycle = 28 days 
 
TABLE OF CONTENTS 
 
 
 
OPEN TO PATIENT ENTRY APRIL 9, 2012; REVISED JULY 9, 2012; TEMPORARILY CLOSED TO PATIENT ENTRY JULY 23, 2012; 
REVISED AUGUST 21, 2012; RE-OPENED TO PATIENT ENTRY OCTOBER 15, 2012; CLOSED TO PATIENT ENTRY NOVEMBER 15, 2012; 
REVISED 
This protocol was designed and developed by the Gynecologic Oncology Group (GOG). It is intended to be used 
only in conjunction with institution-specific IRB approval for study entry. No other use or reproduction is authorized 
by GOG nor does GOG assume any responsibility for unauthorized use of this protocol. 


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TABLE OF CONTENTS 
 
    PAGE 
  
1.0 
OBJECTIVES 
- 4 - 
1.1 
Primary Objectives 
- 4 - 
1.2 
Secondary Objectives 
- 4 - 
1.3 
Translational Research Objectives 
- 4 - 
2.0 
BACKGROUND & RATIONALE 
- 4 - 
2.1 
Ovarian Cancer and PARP Inhibition 
- 4 - 
2.2 
ABT-888 
- 6 - 
2.3 
Translational Research Background 
- 10 - 
2.4 
Inclusion of Women and Minorities 
- 10 - 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS 
- 12 - 
3.1   
Eligibility Criteria 
- 12 - 
3.2 
Ineligibility Criteria 
- 14 - 
4.0 
STUDY MODALITIES 
- 16 - 
4.1 
ABT-888 Capsule, Veliparib, A-861695.0 (IND #77840) (NSC #737664) 
- 16 - 
5.0       TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE 
- 20 - 
5.1   
Patient Entry and Registration 
- 20 - 
5.2 
Treatment Plan 
- 21 - 
5.3 
Criteria for removal from treatment 
- 21 - 
6.0 
TREATMENT MODIFICATIONS 
- 22 - 
6.1 
Hematologic toxicity 
- 22 - 
6.2 
Non-hematologic toxicity 
- 23 - 
6.3 
Dose escalations 
- 24 - 
7.0       STUDY PARAMETERS & SERIAL OBSERVATIONS 
- 24 - 
7.1 
Observations and Tests 
- 24 - 
7.2 
Pathology Requirements 
- 25 - 
7.3 
Translational Research 
- 25 - 
7.4 
Quality of Life 
- 27 - 
8.0 
EVALUATION CRITERIA 
- 28 - 
8.1 
Antitumor Effect – Solid Tumors 
- 28 - 
9.0 
DURATION OF STUDY 
- 36 - 
9.1 
Patients will receive therapy until disease progression or intolerable toxicity intervenes. The 
patient can refuse the study treatment at any time. 
- 36 - 
9.2 
All patients will be treated (with completion of all required case report forms) until disease 
progression, initiation of a subsequent cancer treatment or study withdrawal.  Patients will then be 
followed every three months for the first two years and then every six months for the next three years.  
Patients will be monitored for delayed toxicity and survival for this 5-year period with Q forms 
submitted to the GOG Statistical and Data Center, unless consent is withdrawn.  Q forms will no 
longer be required if the study is terminated prior to the completion of the 5-year follow-up period. - 36 
- 
9.3  
A patient is considered off study therapy when the patient has progressed or died, a subsequent 
drug or therapy (directed at the disease) is initiated or all study therapy is discontinued. Report all 
treatment received on Form D2R and adverse events on Form T until the patient qualifies as being off 
study therapy. 
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10.0 
STUDY MONITORING & REPORTING PROCEDURE 
- 37 - 
10.1 
ADVERSE EVENT REPORTING FOR AN INVESTIGATIONAL AGENT (CTEP IND)- 37 - 
10.2 
GOG DATA MANAGEMENT FORMS 
- 40 - 
11.0     STATISTICAL CONSIDERATIONS 
- 42 - 
11.1 
This is a Phase II study and no randomization is involved, however, patient registration will be 
accomplished in the usual fashion. 
- 42 - 
11.2 
The anticipated annual accrual is 50 patients. 
- 42 - 
11.3 
The study plan is a single arm, 2-stage phase II clinical trial. 
- 42 - 
11.4 
Evaluability for efficacy and toxicity 
- 44 - 
11.5 
Data Safety and Monitoring 
- 44 - 
11.6 
Secondary Endpoints and Exploratory Analyses 
- 45 - 
11.7 
Accrual Targets 
- 46 - 
12.0 
BIBLIOGRAPHY 
- 47 - 
APPENDIX I 
- 49 - 
Appendix II  - GOG General Chemotherapy Guidelines 
- 51 - 
APPENDIX III - PATIENT PILL CALENDAR 
- 52 - 
Appendix IV - Specimen Procedures 
- 54 - 
 
 
 
 
 
 
 
 


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1.0 
OBJECTIVES 
 
1.1 
Primary Objectives 
 
1.11 
To estimate the proportion of patients who have objective tumor response (complete or 
partial). 
 
1.12 
To determine the frequency and severity of adverse events associated with treatment 
with veliparib (ABT-888) as assessed by the Active Version of the National Cancer 
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 
4.0. 
 
1.2 
Secondary Objectives 
 
1.21 
To determine the duration of progression-free survival (PFS) and overall 
survival (OS). 
 
1.22 
To determine the proportion of patients who survive progression-free for at least 
6 months. 
 
1.3 
Translational Research Objectives 
 
1.31 
To explore the association between single nucleotide polymorphisms (SNPs) in 
DNA repair genes (e.g., BRCA1, Fanconi) and clinical characteristics, response, 
and patient outcome (PFS and OS). 
 
2.0 
BACKGROUND & RATIONALE 
 
2.1 
Ovarian Cancer and PARP Inhibition 
 
PARP-1 is essential to the repair of DNA single-strand breaks via the base excision 
repair pathway. Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA repair 
mechanisms by detecting and initiating repair after DNA strand breaks. Inhibition of 
PARP in DNA repair-defective tumors (like those with BRCA1 or BRCA2 mutations) 
can lead to gross genomic instability and cell death.  Recent in vitro and in vivo 
evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy 
sensitizers, but also as single agents to selectively kill cancers defective in DNA repair, 
specifically cancers with mutation in the breast cancer-associated genes, BRCA1 and 
BRCA2. 
 
Much of the proof of concept and proof of principle single agent studies performed to 
date have centered on olaparib.  A phase I study of olaparib in 60 patients with 
advanced solid tumors evaluated doses of olaparib beginning at 10 mg daily, two out of 
three weeks, up to 600 mg BID.  The maximum tolerated dose was deemed to be 400 
mg twice daily.  Objective responses were observed only in confirmed carriers of 
BRCA1 or BRCA2 mutation, apart from one patient with a strong family history of 
BRCA mutation who declined mutational testing.  Of the 60 patients entered, there were 


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9 partial or complete responses by RECIST criteria (8 with ovarian cancer and 1 with 
breast cancer).  Of the 9 responders, 4 received 400 mg BID, 4 received 200 mg BID  
 
and one 100 mg BID.  A total of 21 patients with ovarian cancer and 9 patients with 
breast cancer were entered on the study.1   
 
A phase II trial evaluating two sequential cohorts of women with recurrent ovarian 
cancer (with confirmed germline BRCA1 or BRCA2 mutation and measurable disease) 
enrolled 33 women treated at 400 mg BID and then 24 women treated at 100 mg BID.  
Objective response rate (RECIST) was 33% (11/33 patients) in the 400 mg BID cohort 
and 13% (3/24 patients) in the 100 mg BID cohort.2  A Similar study was performed in 
metastatic breast cancer patients with confirmed germline BRCA1 or BRCA2 mutation 
and measurable disease.  In this study, the objective response rate (RECIST) was 41% 
(11/27 patients) in the 400 mg BID cohort and 22% (6/27 patients) in the 100 mg BID 
cohort.3   
 
In a further phase I study, 50 patients with recurrent ovarian cancer, known BRCA1 or 
BRCA2 mutation and measurable disease were treated with doses of olaparib ranging 
from 40 mg daily for 2 of 3 weeks, to 600 mg BID (11 patients).  There was then a dose 
expansion cohort in which all patients received olaparib at 200 mg BID (39 patients).  
Objective response rate was 28% (14/50 patients).  Objective response rates were 
reported according to platinum-sensitivity:  Platinum-sensitive 46% (6/13 patients); 
Platinum-resistant 33% (8/24 patients); and Platinum-refractory 0% (0/13 patients).4  
A potential explanation for the variable response according to platinum-sensitivity is the 
development of secondary mutations restoring BRCA 1/2 function.5-9   
 
Olaparib has also been evaluated as a single agent in a trial that included patients 
without germline BRCA1 or BRCA2 mutation.  In this phase II trial, 86 patients were 
treated and evaluable for response (63 with ovarian cancer and 23 with breast cancer).  
Patients were entered with recurrent high grade serous and/or undifferentiated ovarian 
cancer or triple negative breast cancer.  Patients were stratified according to whether 
they had a BRCA1 or BRCA2 mutation or not.  In ovarian cancer, objective responses 
were seen in 41% (7/17 patients) with BRCA1 or BRCA2 mutation and 24% (11/46 
patients) without BRCA1 or BRCA2 mutation.  No objective responses were seen in 
breast cancer patients (8 BRCA; 15 non-BRCA).10    
 
A three-arm randomized, open label, phase II trial of olaparib 200 mg BID (n=32), 
olaparib 400 mg BID (n=32) and pegylated liposomal doxorubicin (PLD) (n=33), in 
women with recurrent ovarian cancer, germline BRCA1 or BRCA2 mutation and 
recurrence within 12 months of prior platinum therapy has been conducted.   PLD was 
given at 50 mg/m2 every 4 weeks.  The primary endpoint was investigator assessed 
progression-free survival.  The progression free survival (PFS) and objective response 
rates (RR) were similar between the 3 arms.11  The efficacy of olaparib was consistent 
with previous studies.  The efficacy of PLD was greater than expected. (07/09/2012) 
 
A randomized phase II maintenance trial of olaparib (400 mg BID) vs placebo was 
conducted in women with platinum sensitive recurrent high grade serous ovarian cancer 
(with and without BRCA1 or BRCA2 mutation) who had achieved a response (partial 


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or complete) following 2nd line (or greater) platinum-based therapy. The time to 
progression in the 265 patient cohort was extended from 4.8 months to 8.4 months (HR: 
0.35, P<0.001).  Patients were not required to undergo BRCA1 and BRCA2 testing and 
they were not stratified as to whether they had a BRCA1 or BRCA2 mutation or not.12 
(07/09/2012) 
 
The olaparib formulation used in all the above detailed trials is a 50 mg capsule.  To 
achieve the recommended dose of 400 mg BID, 16 large (size 0) capsules are required 
which may compromise patient convenience and compliance.  In a phase I-
pharmacokinetic study (24 patients), an equivalent tablet formulation dose of olaparib to 
the 400 mg BID capsule formulation (16 capsules) was established as 200 mg BID (4 
tablets).13  This tablet formulation is now entering efficacy trials.     
 
Currently several phase I/II studies with Veliparib are ongoing in combination with 
chemotherapy and/or radiation therapy (50 trials listed in Clincialtrials.gov). (See 
Section 2.22 for details of the phase I clinical experience) Currently, in recurrent 
ovarian cancer, Veliparib is being combined with temozolomide in a randomized phase 
II study versus PLD (Doxil) in women with recurrent serous ovarian cancer 
(NCT01113957); and in combination with metronomically delivered cyclophosphamide 
versus sequential metronomic cyclophosphamide and Veliparib in patients with 
recurrent serous ovarian cancer (NCT01306032). The GOG is also conducting a phase I 
trial in combination with bevacizumab and the cytotoxic agents, paclitaxel and 
carboplatin in frontline ovarian cancer (GOG9923; NCT00989651).  The dosing and 
schedule under each of these trials is profoundly influenced by the agents being co-
administered.  Currently, there are no clinical efficacy data of single agent 
Veliparib, which is the primary objective of the current proposal. 
The single agent, dose-finding, phase I trial of ABT-888 is still ongoing 
(NCT00892736).  This study is open to BRCA1 and BRCA2 mutation carriers, triple 
negative metastatic breast cancer, platinum-refractory ovarian cancer, pancreatic cancer, 
prostate cancer patients.  The primary goal of the study is to determine the 
recommended phase II dose.  The requirement for entered ovarian cancer patients to 
have platinum-refractory disease is concerning, as this is the group previously shown 
not to respond to olaparib, even when entry criteria were restricted to BRCA1 and 
BRCA2 carriers.4  Thus a true evaluation of the activity of veliparib in recurrent, 
measurable disease, BRCA1 or BRCA2 mutation ovarian cancer has not been under 
taken. 
 
2.2 
ABT-888 
 
ABT-888 is a potent PARP inhibitor that delays the repair of DNA damage induced by 
chemotherapeutics.  ABT-888 increases sensitivity of tumor cells to DNA damaging 
agents in vitro, and demonstrates PARP inhibition in murine tumors in vivo and human 
peripheral blood mononuclear cells (PBMCs) ex vivo. 
 
ABT-888 is a novel small molecule that is a potent inhibitor of both PARP-1 and PARP 
2, with Ki‘s of 5 nM and 3 nM, respectively.  In cells under oxidative stress, ABT-888 
inhibits the PARP-induced formation of poly-(ADP-ribose) (PAR) with an EC50 of 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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2.4nM.  Consistent with the conclusion of mechanism based efficacy, significant 
inhibition of PAR levels was observed with doses of ABT-888 capable of delivering 
significant anti-tumor efficacy in preclinical models.  A facile, enzyme-linked 
immunosorbent assay (ELISA) for measurement of PAR formation has been developed 
that can be used for analysis of pharmacodynamic effects of ABT-888 in human PBMC 
and tumor clinical samples.14,15 
 
In cellular assays, ABT-888 increases sensitivity of tumor cells to DNA-damaging 
agents including temozolomide (TMZ), irinotecan, cyclophosphamide, BCNU, 
cisplatin, and radiation.  In pre-clinical tumor models, ABT-888 enhances the anti-
tumor efficacy of alkylating/methylating agents (TMZ, cyclophosphamide), cross-
linking agents (cisplatin, carboplatin), topoisomerase inhibitors (irinotecan), and 
radiation.  
 
2.21  Pre-Clinical Experience 
 
2.211  Pharmacokinetics 
 
In rats and dogs, ABT-888 is primarily cleared in the urine as intact 
parent drug, with minor contributions from metabolism.  The renal 
clearance and minimal metabolism observed in rats and dogs, and the 
minimal metabolism observed in vitro in all species evaluated are 
consistent with the low molecular weight (244.296 g/mol) and good 
solubility of ABT-888.  These data support the prediction that in 
humans, ABT-888 will be primarily cleared as intact parent in urine. 
 
ABT-888 is not a potent inhibitor, nor an inducer, of the major human 
cytochrome P450s (CYPs), suggesting a minimal potential for drug-drug 
interactions at the anticipated therapeutic concentrations. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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NCI Version Date:  05/02/2016                                                                                                                              
 
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2.22  Clinical Experience 
 
A Phase 0 dose-ranging pharmacokinetic and pharmacodynamic study has been 
completed (NCI IND).  In this trial, 13 subjects with various types of advanced 
cancer received a single dose of single-agent ABT-888 (10 mg, n = 3; 25 mg, n 
= 3; 50 mg, n = 7).  The pharmacokinetic results from this study demonstrated 
that ABT-888 is orally bioavailable and primarily cleared through renal 
excretion, with a half-life of 4 to 5 hours.  Additionally, this study provided 
proof of mechanism, as tumor PARP inhibition (> 90%) was demonstrated in 5 
out of 6 human tumor biopsies that were obtained 3 to 6 hours after dosing with 
ABT-888.   No serious adverse events, dose-limiting toxicities (DLTs), or deaths 
were reported for this study.16 
 
Multiple Phase I studies of ABT-888 in combination with various 
chemotherapeutic agents are on-going. Study M06-862 is a dose-escalation 
study designed to assess the safety, tolerability, and pharmacokinetic profile of 
ABT-888 in combination with TMZ.  
 


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The A10-153 study is a Phase I study designed to assess the safety and 
tolerability of ABT-888 in combination with carboplatin/paclitaxel.  In this trial 
ABT-888 is given orally on Days 1-7, and carboplatin/paclitaxel are given on 
Day 3 of a 21-day cycle.  The trial is accruing subjects to the dose level of 40 
mg ABT-888 plus carboplatin (AUC=6) and paclitaxel (200 mg/m2). Thus far, 
the treatment has been tolerated well with heavily pre-treated patients receiving 
a median number of 6 cycles on study.  Of the six patients treated at carboplatin 
AUC 6, paclitaxel 175 mg/m2 and ABT-888 40 mg BID, three were able to 
complete all 6 cycles at the full dose.  Three patients required dose reductions of 
paclitaxel secondary side effects.  The MTD has not been reached in this study.  
An additional Phase I dose escalation study of ABT-888 monotherapy in BRCA 
carriers with solid tumors is ongoing.  Treatment in this study is continuous BID 
dosing beginning at a dose of 50 mg BID.  The recommended phase II dose 
from this continuous monotherapy study is 300 to 400 mg BID.  Patients can 
experience nausea.  If nausea is seen with the 400 mg BID dose, the 
recommendation is to lower the dose to 300 mg BID (Personal Communication:  
Alice Chen, MD and Shannon Puhalla, MD). 
 
2.3 
Translational Research Background 
 
Polymorphisms in Fanconi pathway genes may alter DNA repair efficiency. This 
alteration may predispose individuals to sensitivity to PARP inhibition. Thus, the 
optional translational research component of this study will examine single nucleotide 
polymorphisms (SNPs) in DNA repair genes. To examine SNPs that may alter DNA 
repair efficiency, formalin-fixed, paraffin-embedded tumor and whole blood will be 
collected from patients who agree to participate. SNPs in DNA repair genes (e.g., 
BRCA1, Fanconi) will be examined using the best platform identified at the time of 
testing. The association between SNPs and response, survival, and clinical 
characteristics will be examined. 
 
2.4 
Inclusion of Women and Minorities 
 
The Gynecologic Oncology Group (GOG) and GOG participating institutions will not 
exclude potential subjects from participating in this or any study solely on the basis of 
ethnic origin or socioeconomic status.  Every attempt will be made to enter all eligible 


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patients into this protocol and therefore address the study objectives in a patient 
population representative of the entire ovarian, fallopian tube, and primary peritoneal 
cancer population treated by participating institutions. 


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3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS 
 
3.1   
Eligibility Criteria 
 
3.11 
Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or 
primary peritoneal carcinoma AND carry a germline mutation in BRCA1 or 
BRCA2 (confirmation required via genetic test report).  Histologic 
documentation of the original primary tumor is required via the pathology 
report. (07/09/2012) 
 
3.12 
All patients must have measurable disease as defined by RECIST 1.1. 
Measurable disease is defined as at least one lesion that can be accurately 
measured in at least one dimension (longest diameter to be recorded).  Each 
lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by 
clinical exam; or ≥ 20 mm when measured by chest x-ray.  Lymph nodes must 
be > 15 mm in short axis when measured by CT or MRI. 
 
3.13 
Patient must have at least one “target lesion” to be used to assess response on 
this protocol as defined by RECIST 1.1 (Section 8.1).  Tumors within a 
previously irradiated field will be designated as “non-target” lesions unless 
progression is documented or a biopsy is obtained to confirm persistence at least 
90 days following completion of radiation therapy. 
 
3.14 
Patients who have received one prior cytotoxic regimen must have a GOG 
Performance Status of 0, 1, or 2. 
 
 
Patients who have received two or three prior cytotoxic regimens must have a 
GOG Performance Status of 0 or 1. 
 
3.15 
Recovery from effects of recent surgery, radiotherapy, or chemotherapy 
 
3.151 Patients should be free of active infection requiring antibiotics (with the 
exception of uncomplicated UTI). 
 
3.152 Any hormonal therapy directed at the malignant tumor must be 
discontinued at least one week prior to registration.  Continuation of 
hormone replacement therapy is permitted. 
 
3.153 Any other prior therapy directed at the malignant tumor, including 
chemotherapy, biologic/targeted (non-cytotoxic) agents and 
immunologic agents, must be discontinued at least three weeks prior to 
registration.  Patients receiving nitrosoureas or mitomycin C must 
discontinue 6 weeks prior to registration. 
 
3.154 Any prior radiation therapy must be discontinued at least four weeks 
prior to registration. 
 
 


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3.16 
Prior therapy 
 
3.161 Patients must have had one prior platinum-based chemotherapeutic 
regimen for management of primary disease containing carboplatin, 
cisplatin, or another organoplatinum compound.  This initial treatment 
may have included intraperitoneal therapy, consolidation, 
biologic/targeted (non-cytotoxic) agents or extended therapy 
administered after surgical or non-surgical assessment. 
 
3.162 Patients are allowed to receive, but are not required to receive, two 
additional cytotoxic regimens for management of recurrent or persistent 
disease. 
 
 
3.163 Patients are allowed to receive, but are not required to receive, 
biologic/targeted (non-cytotoxic) therapy for management of recurrent or 
persistent disease.  Patients are allowed to receive, but are not required to 
receive, biologic/targeted (non-cytotoxic) therapy as part of their primary 
treatment regimen. 
 
3.164 Patients with both platinum-sensitive and platinum-resistant disease are 
eligible.  Patients with platinum-refractory disease are NOT eligible. 
 
Definitions: 
• Platinum sensitive ovarian cancer is defined as patients who respond 
to platinum-based therapy (complete or partial) and then 
progress/recur more than 6 months after their last platinum dose (i.e., 
platinum-free interval is > 6 months). 
• Platinum resistant ovarian cancer is defined as patients who respond 
to platinum-based therapy (complete or partial) and then 
progress/recur within 6 months of their last platinum dose (i.e., 
platinum-free interval is <= 6 months). 
• Platinum refractory ovarian cancer is defined as patients who have 
progression of disease while receiving platinum-based chemotherapy 
or who fail to achieve at least a partial response to platinum-based 
chemotherapy (i.e., best response to platinum-based chemotherapy is 
stable disease).   
 
 
 
3.17 Patients must have adequate: 
 
3.171 Bone marrow function: Absolute neutrophil count (ANC) greater than or 
equal to 1,500/mcl.  Platelets greater than or equal to 100,000/mcl. 
 
3.172 Renal function:  Creatinine less than or equal to 1.5 x institutional upper 
limit normal (ULN).  
 


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3.173 Hepatic function: Bilirubin less than or equal to 1.5 x ULN.  AST and 
ALT less than or equal to 3 x ULN.  Alkaline phosphatase less than or 
equal to 2.5 x ULN. 
 
3.18 
Patients must have signed an approved informed consent and authorization 
permitting release of personal health information. 
 
3.19 
Patients must meet pre-entry requirements as specified in section 7.0. 
 
3.110 Patients of childbearing potential must have a negative pregnancy test prior to 
the study entry and be practicing an effective form of contraception. 
 
3.111 Patients must be 18 years or older. 
 
3.2 
Ineligibility Criteria 
 
3.21 
Patients who have had previous treatment with veliparib (ABT-888) or any other 
PARP inhibitor (including olaparib).  Note:  Iniparib (BSI-201) cannot inhibit 
PARP1 at pharmacologically achievable concentrations, therefore prior iniparib 
therapy is allowed. 
 
3.22 
Patients with a history of other invasive malignancies, with the exception of 
non-melanoma skin cancer and other specific malignancies as noted in Sections 
3.23 and 3.24, are excluded if there is any evidence of other malignancy being 
present within the last three years. Patients are also excluded if their previous 
cancer treatment contraindicates this protocol therapy. 
 
3.23 
Patients who have received prior radiotherapy to any portion of the abdominal 
cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or 
primary peritoneal cancer within the last three years are excluded. Prior 
radiation for localized cancer of the breast, head and neck, or skin is permitted, 
provided that it was completed more than three years prior to registration, and 
the patient remains free of recurrent or metastatic disease.  
 
3.24 
Patients who have received prior chemotherapy for any abdominal or pelvic 
tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary 
peritoneal cancer within the last three years are excluded. Patients may have 
received prior adjuvant chemotherapy for localized breast cancer, provided that 
it was completed more than three years prior to registration, and that the patient 
remains free of recurrent or metastatic disease.  
 
3.25 
Patients with seizures or history or seizures are ineligible. 
 
Patients with history or evidence upon physical examination of CNS disease, 
including primary brain tumor, , any CNS metastases, or history of 
cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or 
subarachnoid hemorrhage within six months of the first date of treatment on this 


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study are ineligible.  Patients with CNS metastases must be stable for >3 months 
after treatment and off steroid treatment prior to study enrollment. (08/21/2012) 
 
3.26 
Inability or unwillingness to swallow pills. 
 
3.27 
Patients with clinical symptoms or signs of gastrointestinal obstruction and/or 
who require parenteral hydration or nutrition. 
 
3.28 
Patients who are pregnant or nursing. 
 
 


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4.0 
STUDY MODALITIES 
 
4.1 
ABT-888 Capsule, Veliparib, A-861695.0 (IND #77840) (NSC #737664) 
 
4.11 
Chemical Name/Molecular Formula: 1H-Benzimidazole-7-carboxamide, 2-
[(2R)-2-methyl-2-pyrrolidinyl]- 
 
 
C13H16N4O  
M.W.:  244.29 
 
 
 
 
     
  
 
 
 
 
 
 
 
4.13 
Mode of Action: ABT-888 inhibits the formation of poly (ADP-ribose) (PAR) 
polymers in vitro and in vivo.  It inhibits the repair of DNA when the DNA is 
damaged by cytotoxic agents.  ABT-888 increases antitumor efficacy when 
added to DNA-damaging therapies such as temozolomide, cisplatin, carboplatin, 
cyclophosphamide, irinotecan, or radiation therapy.  
 
 
 
 
 
 
 
 
4.16 
Route of Administration: Oral 
 
 
  
 
 
 
 
   
   
4.19 
Potential Drug Interactions: Clinical studies evaluating the metabolism of ABT-
888 have not been conducted.  However, results from the in vitro analysis reveal 
that this agent is metabolized by multiple isoenzymes – CYP1A1, 2D6, 2C19 
and 3A4.  ABT-888 is neither a potent inhibitor nor a potent inducer of the 


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CYP-450 isoenzymes.  Use caution when concomitantly administered with 
drugs that are substrate, inhibitor, inducer of CYP1A1, 2D6, 2C19 and 3A4. 
 
 
ABT-888 clears primarily in the urine as intact parent drug along with 
metabolites suggesting that renal function plays an important role in the drug 
clearance and its metabolites. Use caution when concomitantly administered 
with oxaliplatin, carboplatin, cisplatin, and topotecan in patients with pre-
existing renal impairment.  
 
 
 
 
 
4.110 Drug Ordering and Accountability: NCI-supplied agents may be requested by 
the Principal Investigator (or their authorized designee) at each participating 
institution.  Pharmaceutical Management Branch (PMB) policy requires that 
agent be shipped directly to the institution where the patient is to be treated.  
PMB does not permit the transfer of agents between institutions (unless prior 
approval from PMB is obtained).  The CTEP-assigned protocol number must be 
used for ordering all CTEP-supplied investigational agents.  The responsible 
investigator at each participating institution must be registered with CTEP, 
DCTD through an annual submission of FDA Form 1572 (Statement of 
Investigator), Curriculum Vitae, Supplemental Investigator Data Form (IDF), 
and Financial Disclosure Form (FDF).  If there are several participating 
investigators at one institution, CTEP-supplied investigational agents for the 
study should be ordered under the name of one lead investigator at that 
institution. 
 
 
 
 
 
 
 
Active CTEP-registered investigators and investigator-designated shipping 
designees and ordering designees can submit agent requests through the PMB 
Online Agent Order Processing (OAOP) application (https://eapps-
ctep.nci.nih.gov/OAOP/pages/login.jspx).  Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account 
(https://eapps-ctep.nci.nih.gov/iam/) and the maintenance of an “active” account 
status and a “current” password.  For questions about drug orders, transfers, 
returns, or accountability, call 240-276-6575 Monday through Friday between 
8:30 am and 4:30 pm (ET) or email PMBAfterHours@mail.nih.gov anytime. (  ) 
 
4.111 Agent Inventory Records: The investigator, or a responsible party designated by 
the investigator, must maintain a careful record of the inventory and disposition 
of all agents received from DCTD using the NCI Drug Accountability Record 
Form (DARF).  (See the NCI Investigator’s Handbook for Procedures for Drug 
Accountability and Storage.) 
 
 
 
4.112 Comprehensive Adverse Events and Potential Risks list (CAEPR) For Veliparib 
(ABT-888, NSC 737664) (08/21/2012) (  ) 
 
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a 
single list of reported and/or potential adverse events (AE) associated with an 
agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Specific Protocol Exceptions to Expedited 
Reporting (SPEER), appears in a separate column and is identified with bold 


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and italicized text. This subset of AEs (SPEER) is a list of events that are 
protocol specific exceptions to expedited reporting to NCI via AdEERS (except 
as noted below).  Refer to the 'CTEP, NCI Guidelines: Adverse Event Reporting  
Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguid
elines.pdf for further clarification.  Frequency is provided based on 2310 
patients. Below is the CAEPR for Veliparib (ABT-888). 
 
NOTE: Report AEs on the SPEER ONLY IF they exceed the grade noted in parentheses next to 
the AE in the SPEER.  If this CAEPR is part of a combination protocol using multiple 
investigational agents and has an AE listed on different SPEERs, use the lower of the grades to 
determine if expedited reporting is required. 
 
Version 2.3, March 4, 20161 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
  
 
 
 
 
  
 


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1This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all Principal 
Investigators at the time of revision.  The current version can be obtained by contacting PIO@CTEP.NCI.NIH.GOV.  Your 
name, the name of the investigator, the protocol and the agent should be included in the e-mail. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


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5.0       TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE  
 
Sites must submit all IRB approvals (initial and continuing) on NCI- sponsored adult 
Cooperative Group phase I, II & III prevention and treatment studies to the CTSU Regulatory 
Office, at the Coalition of Cancer Cooperative Groups in Philadelphia. A CTSU 
IRB/Regulatory Approval Transmittal Sheet should be submitted along with the CTSU IRB 
Certification Form or its equivalent. (CTSU forms can be downloaded at 
https://www.ctsu.org/public/rss2_page.aspx).  IRB submissions can be faxed or e mailed 
(preferred methods) or mailed to: 
 
Cancer Trials Support Unit (CTSU) 
ATTN: Coalition of Cancer Cooperative Groups (CCCG) 
Suite1100 
1818 Market Street 
Philadelphia, PA 19103 
FAX: 1-215-569-0206 
CTSURegulatory@ctsu.coccg.org 
 
5.1   
Patient Entry and Registration 
 
When a suitable candidate has been identified for protocol entry, the following steps 
should be taken: 
 
OPEN Registration: All site staff will use OPEN to enroll patients to this 
study.  OPEN can be accessed on the GOG web menu page by clicking on the OPEN 
link.  
  
Prior to accessing OPEN site staff should verify the following: 
  
• 
All eligibility criteria have been met within the protocol stated timeframes. Site 
staff should use the registration forms provided on the group web site as a tool 
to verify eligibility. 
• 
Sites will provide documentation of germline BRCA 1 or 2 mutation status 
• 
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable).  
  
Access requirements for OPEN: 
  
• 
Site staff will need to be registered with CTEP and have a valid and active 
CTEP-IAM account. This is the same account (user id and password) used for 
the CTSU members' web site.  
• 
To perform registrations, the site user must have been assigned the 'Registrar' 
role on the GOG or CTSU roster.  
• 
To perform registrations you must have an equivalent 'Registrar' role on the 
Lead Group roster.  Role assignments are handled through the Groups in which 
you are a member.  
  


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Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information.   Please print this confirmation for your records.  
  
Further instructional information is provided on the CTSU members' web site OPEN tab 
or within the OPEN URL. For any additional questions contact the CTSU Help Desk at 
1-888-823-5923 or ctsucontact@westat.com.  
 
            5.2 
Treatment Plan 
 
 
 
5.21 
Treatment: 
 
Veliparib 400 mg will be taken orally twice daily (about the same time every 
day).  The doses should be taken about 12 hours apart. 
 
If a patient is more than 4 hours late in taking a dose, the dose should be 
skipped. 
 
Pills may be taken with or without food.  Pills should be swallowed with 
approximately 8 ounces of water. 
 
One cycle = 28 days.  Patients will receive therapy until disease progression or 
adverse effects prohibit further therapy. 
 
Patients will self administer Veliparib and record doses on a pill calendar.  See 
Patient Pill Calendar (Appendix III).  Patients should be instructed to bring any 
unused pills, pill bottles and completed pill calendar to each appointment. 
 
 
 
5.22 
See the GOG General Chemotherapy Guidelines (Appendix II) 
 
5.3 
Criteria for removal from treatment 
 
 
5.31 
Inability to tolerate veliparib (ABT-888) at the lowest doses because of toxicity. 
 
 
5.32 
Patients who experience a seizure while on study should be removed from study 
therapy. 
 
 
5.33 
Patients who become pregnant while on study should be removed from study 
therapy. 
 
 
5.34 
Patients may withdraw from the study at any time for any reason.  Patients with 
evidence of disease progression or significant side effects will be removed from 
study. 


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6.0 
TREATMENT MODIFICATIONS 
 
 
Study Drug  
2 Level reduction 
1 Level reduction 
Initial dose level 
 
ABT-888 
200 mg oral twice 
daily 
300 mg oral twice 
daily 
400 mg oral twice 
daily 
 
Please note:  Patients may manifest nausea.  Dose reduction for non-tolerable grade 1-2 
nausea is allowed.  Dose reductions can be made during a treatment cycle or at the start 
of the next cycle.  Dose reduction is preferable to prolonged treatment interruption or 
study discontinuation.  Grade 3 (or greater) nausea requires reduction of one dose level 
and delay in subsequent therapy for a maximum of 3 weeks until recovered to grade 1.  
See section 6.21. 
 
Please note all CTCAE grading below refers to version 4.0. 
 
A maximum of two dose reductions is allowed for each patient.  Patients experiencing 
toxicity (hematologic or non-hematologic) that meets criteria for further dose reduction, 
after this maximum, will be removed from study therapy. 
 
6.1 
Hematologic toxicity 
 
6.11 
Initial treatment modifications will consist of cycle delay and/or dose reduction 
as indicated below. The use of hematopoietic cytokines and protective reagents 
are restricted as noted: 
 
6.111 Patients will NOT receive prophylactic G-CSF. 
 
6.112 Patients will NOT receive prophylactic thrombopoietic agents. 
 
6.113 Patients may receive erythropoietin (EPO), iron supplements, and/or 
transfusions as clinically indicated for management of anemia. Treating 
physicians should be aware of the recent changes in prescribing 
information for the erythropoiesis stimulating agents (including Aranesp, 
Epogen and Procrit) which note that there is a potential risk of shortening 
the time to tumor progression or disease-free survival, and that these 
agents are administered only to avoid red blood cell transfusions. They 
do not alleviate fatigue or increase energy. They should not be used in 
patients with uncontrolled hypertension. They can cause an increased 
incidence of thrombotic events in cancer patients on chemotherapy. The 
updated package inserts should be consulted.   
http://www.fda.gov/Medwatch/safety/2007/safety07.htm  
 
6.12 
Treatment decisions will be based on the absolute neutrophil count (ANC) rather 
than the total white cell count (WBC). 
 


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6.13 
Subsequent cycles of therapy will not begin until the ANC is ≥ 1500 cells/mcl 
and the platelet count is ≥ 100,000/mcl.  Therapy will be delayed for a 
maximum of three weeks until these values are achieved.  Patients who achieve 
adequate counts after a delay will receive ABT-888 with a 1 dose level 
reduction. Patients who fail to recover adequate counts within three weeks will 
be removed from study therapy. 
 
6.14 
For febrile neutropenia, and/or documented grade 4 neutropenia persisting ≥ 7 
days, reduce ABT-888 by one dose level on subsequent cycles. 
 
6.15 
There will be no dose modifications on the basis of uncomplicated granulocyte 
nadirs lasting less than 7 days. 
 
6.16 
Patients with grade 3 or 4 thrombocytopenia or active bleeding will have a 1 
level dose reduction. 
 
 
6.2 
Non-hematologic toxicity 
 
6.21 
Patients may manifest nausea.  Dose reduction for non-tolerable grade 1-2 
nausea is allowed.  Dose reductions can be made during a treatment cycle or at 
the start of the next cycle.  Dose reduction is preferable to prolonged treatment 
interruption or study discontinuation.  Grade 3 (or greater) nausea requires 
reduction of one dose level and delay in subsequent therapy for a maximum of 3 
weeks until recovered to grade 1.   
 
6.22 
Grade 2 (or greater) peripheral neuropathy requires reduction of one dose level 
and delay in subsequent therapy for a maximum of 3 weeks until recovered to 
grade 1. 
 
6.23 
Grade 2 (or greater) renal toxicity (and elevations in creatinine), requires 
reduction of one dose level and delay in subsequent therapy for a maximum of 3 
weeks until recovered to grade 1. 
 
6.24 
Grade 3 (or greater) elevations in AST, ALT, alkaline phosphatase or bilirubin 
requires reduction of one dose level and delay in subsequent therapy for a 
maximum of 3 weeks until recovered to grade 1. 
 
6.25 
There will be no dose modifications for alopecia or fatigue. 
 
 
6.26 
It is expected that patients with diarrhea or constipation will receive appropriate 
medical management without dose modification. However, patients with 
persistent (greater than 24 hours) grade 3 (or greater) toxicity in spite of optimal 
medical management require reduction of one dose level and delay in 
subsequent therapy for a maximum of 3 weeks until recovered to grade 1. 
 


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6.27 
Other non-hematologic toxicities with an impact on organ function of grade 2 
(or greater) require reduction of one dose level and delay in subsequent therapy 
for a maximum of 3 weeks until recovered to grade 1, or pre-therapy baseline. 
 
6.3 
Dose escalations 
 
There will be no dose escalations or re-escalations on this study. 
 
7.0       STUDY PARAMETERS & SERIAL OBSERVATIONS 
 
7.1 
Observations and Tests 
The following observations and tests are to be performed and recorded on the 
appropriate form(s). Specimen requirements for translational research are provided 
in Section 7.3. 
 
 
Parameter 
 
 
Pre-
Therapy 
Prior to 
Each cycle 
Every  
Other  
Cycle 
 
Off of all study therapy 
History & Physical 
1 
X 
 
 
Vital Status 
 
 
 
7 
Performance status 
1 
 
 
 
Toxicity Assessment 
2 
X 
 
7, 8 
CBC/Differential/Platelets 
2 
4 
 
 
Electrolytes, BUN, creatinine, 
Ca, Mg 
2 
X 
 
 
Urinalysis 
2 
 
 
 
Bilirubin, AST, ALT,  
Alkaline Phosphatase 
2 
X 
 
 
Pregnancy test (for patients of 
child bearing potential) 
3 
 
 
 
Chest imaging (X-ray or CT of 
the chest) 
1 
 
5 
5† 
Radiographic tumor 
measurement 
1, 6 
 
6 
6† 
CA-125 
2 
X 
 
 
Genetic Testing Report(s) 
(BRCA) (07/09/2012) 
9 
 
 
 
Electrocardiogram (ECG) 
1 
 
 
 


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Patient Pill Calendar 
 
10 
 
 
 
†       Until disease progression or until patient initiates a subsequent cancer therapy  
 
Notes: 
 
1. Must be obtained within 28 days prior to initiating protocol therapy. 
2. Must be obtained within 14 days prior to initiating protocol therapy. 
3. Must be obtained within 7 days prior to initiating protocol therapy. 
4. CBC/Differential/Platelets must be obtained within 4 days before re-treatment with protocol therapy. 
 
 
5. Repeat chest imaging if initially abnormal or if required to monitor tumor response.  CT scan to follow 
lesion for measurable disease every other cycle (or equivalent time frame for patients off treatment prior to 
disease progression) for the first 6 months; then every 3 months thereafter until disease progression is 
confirmed; also repeat at any other time if clinically indicated based on symptoms or physical signs 
suggestive of progressive disease.  Responses (CR and PR) require confirmation at greater than or equal to 4 
weeks from initial documentation (see section 8).  
6. CT scan or MRI every other cycle (or equivalent time frame for patients off treatment prior to disease 
progression) for the first 6 months; then every 3 months thereafter until disease progression is confirmed; 
also repeat at any other time if clinically indicated based on symptoms or physical signs suggestive of 
progressive disease.  Responses (CR and PR) require confirmation at greater than or equal to 4 weeks from 
initial documentation (see section 8).  
7. Follow-up every 3 months for 2 years and then every 6 months for 3 years.  Follow-up forms (Form Q) are 
collected for the 5 year follow-up period or until study termination. 
8. Report all adverse events that occur within 30 days of last protocol treatment on the T form for the last cycle 
of therapy administered.  For reporting of delayed toxicity, see section 10.14. 
9. Patients enrolled on this trial are required to have a known germline mutation in BRCA1 or BRCA2. 
Submission of the reports detailing this testing is required.  The following is the usual method for BRCA 
testing: If the patient is of Ashkenazi Jewish/Eastern European Jewish descent, testing begins with 
Multisite3 BRCAnalysis, continuing on to (“Reflex to”) Comprehensive BRCAnalysis if negative. Testing 
of non-Ashkenazi patients starts with Comprehensive BRCAnalysis.  Patients who are negative for the 
above testing can have BRCAnalysis Rearrangement Testing (BART).  Genetic counseling is strongly 
recommended before and after BRCA1/2 testing.  
10. See Appendix III. 
 
 
7.2 
Pathology Requirements 
 
7.21 
Pathology report for histologic confirmation of primary tumor 
 
7.22 
Pathology report for recurrent or persistent disease if histologically documented. 
 
7.23 
Stained slides to confirm eligibility by Central Pathology Committee Review are 
not required for this protocol. 
 
7.3 
Translational Research 
 
If the patient gives permission for her specimens to be collected and used for 
this optional translational research component, then participating institutions 


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are required to submit the patient’s specimens as outlined below (unless 
otherwise specified). 
 
Required Specimen 
(Specimen Code) 
Collection Time Point 
Ship To 
Pre-Treatment FFPE 
Recurrent Tumor (FR01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Prior to Veliparib treatment 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment FFPE 
Metastatic Tumor (FM01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Prior to Veliparib treatment 
(may be archival pre-
treatment) 
 
If FR01or FP01 cannot be 
submitted 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment FFPE Primary 
Tumor (FP01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Archival pre-treatment 
 
If FR01 or FM01 cannot be 
submitted 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment Frozen 
Recurrent Tumor (RR01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Prior to Veliparib treatment 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Frozen 
Metastatic Tumor (RM01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Prior to Veliparib treatment 
(may be archival pre-
treatment) 
 
If RR01or RP01 cannot be 
submitted 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Frozen Primary 
Tumor (RP01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Archival pre-treatment 
 
If RR01 or RM01 cannot be 
submitted 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Serum (SB01) 
prepared from 7-10mL blood 
drawn into a plain red top tube 
Prior to Veliparib treatment 
GOG Tissue Bank within 2 
weeks of registration1 
Whole Blood (WB01) 
7-10mL drawn into purple top 
(EDTA) tube(s) 
Prior to or after initiating 
Veliparib treatment 
GOG Tissue Bank the day the 
blood is collected1 
Post-Treatment FFPE Biopsy, 
FNA or surgical resection 
(FR02) 
1st Choice: Block 
Optional - Post-treatment, if 
patient has biopsy, FNA or 
surgery at time of progression 
as part of standard care 
GOG Tissue Bank within 32 
weeks of registration1 


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2nd Choice: Unstained Slides 
(10 5µm charged ; 10 10µm 
uncharged, if possible) 
(07/09/2012) 
Post-Treatment FFPE Cell 
Pellet from Peritoneal Fluid 
(PF01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged ; 10 10µm 
uncharged, if possible) 
Optional - Post-treatment, if 
patient has peritoneal fluid 
removed at time of 
progression as part of standard 
care (07/09/2012) 
 
If FR02 cannot be submitted 
GOG Tissue Bank within 32 
weeks of registration1 
1 
GOG Tissue Bank / Protocol GOG-0280, Nationwide Children’s Hospital, 700 Children’s Drive, WA1340, Columbus, OH 
43205, Phone: (614) 722-2865, FAX: (614) 722-2897, Email: GOGBanc@nationwidechildrens.org 
 
7.31 
Laboratory Testing 
 
Formalin-fixed, paraffin-embedded specimens and DNA isolated from whole 
blood will be shipped to Drs. Michael Birrer and Elizabeth Swisher for analysis 
of single nucleotide polymorphisms (SNPs) in DNA repair genes (e.g., BRCA1, 
Fanconi). SNP analysis will be run using the best platform identified at the time 
of testing. 
 
Serum will be banked for future research. 
 
 
 
7.32 
Future Research 
 
Details regarding the banking and use of specimens for future research can be 
found in Appendix IV. 
 
7.4 
Quality of Life 
 
 
Not applicable. 


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8.0 
EVALUATION CRITERIA 
 
8.1 
Antitumor Effect – Solid Tumors 
 
Response and progression will be evaluated in this study using the new international 
criteria proposed by the revised Response Evaluation Criteria in Solid Tumors 
(RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].  Changes in the largest 
diameter (unidimensional measurement) of the tumor lesions and the shortest diameter 
in the case of malignant lymph nodes are used in the RECIST criteria. 
 
 
8.11 
Disease Parameters 
 
Measurable disease.  Measurable lesions are defined as those that can be 
accurately measured in at least one dimension (longest diameter to be recorded) 
as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers 
by clinical exam.  All tumor measurements must be recorded in decimal 
fractions of centimeters. 
 
Note:  Tumor lesions that are situated in a previously irradiated area will not be 
considered measurable unless progression is documented or a biopsy is obtained 
to confirm persistence at least 90 days following completion of radiation 
therapy. 
 
Malignant lymph nodes.  To be considered pathologically enlarged and 
measurable, a lymph node must be >15 mm in short axis when assessed by CT 
scan (CT scan slice thickness recommended to be no greater than 5 mm).  At 
baseline and in follow-up, only the short axis will be measured and followed. 
 
Non-measurable disease.  All other lesions (or sites of disease), including small 
lesions (longest diameter <10 mm or pathological lymph nodes with ≥ 10 to <15 
mm short axis), are considered non-measurable disease.  Leptomeningeal 
disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, 
inflammatory breast disease, and abdominal/pelvic masses (identified by 
physical exam and not CT or MRI), are considered as non-measurable. 
 
Notes: 
Bone lesions:  Lytic bone lesions or mixed lytic-blastic lesions, with identifiable 
soft tissue components, that can be evaluated by CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of 
measurability described above.  Blastic bone lesions are non-measurable. 
 
Cystic lesions that meet the criteria for radiographically defined simple cysts 
should not be considered as malignant lesions (neither measurable nor non-
measurable) since they are, by definition, simple cysts.  ‘Cystic lesions’ thought 
to represent cystic metastases can be considered as measurable lesions, if they 
meet the definition of measurability described above. However, if non-cystic 
lesions are present in the same patient, these are preferred for selection as target 
lesions. 


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Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ 
and 5 lesions in total, representative of all involved organs, should be identified 
as target lesions and recorded and measured at baseline.  Target lesions should 
be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, and in addition should be those that lend 
themselves to reproducible repeated measurements.  It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in 
which circumstance the next largest lesion which can be measured reproducibly 
should be selected.  A sum of the diameters (longest for non-nodal lesions, short 
axis for nodal lesions) for all target lesions will be calculated and reported as the 
baseline sum diameters.  If lymph nodes are to be included in the sum, then only 
the short axis is added into the sum.  The baseline sum diameters will be used as 
reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. 
 
Non-target lesions.  All other lesions (or sites of disease) including any 
measurable lesions over and above the 5 target lesions should be identified as 
non-target lesions and should also be recorded at baseline.  Measurements of 
these lesions are not required, but the presence, absence, or in rare cases 
unequivocal progression of each should be noted throughout follow-up.  
 
 
8.12 
Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler 
or calipers.  All baseline evaluations should be performed as closely as possible 
to the beginning of treatment and never more than 4 weeks before the beginning 
of the treatment. 
 
The same method of assessment and the same technique should be used to characterize each identified and reported 
lesion at baseline and during follow-up. Imaging-based evaluation is preferred to evaluation by clinical examination 
unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam. 
 
Clinical lesions: Clinical lesions will only be considered measurable when they 
are superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm 
diameter as assessed using calipers (e.g., skin nodules).  In the case of skin 
lesions, documentation by color photography, including a ruler to estimate the 
size of the lesion, is recommended.  
 
Chest x-ray: Lesions on chest x-ray are acceptable as measurable lesions when 
they are clearly defined and surrounded by aerated lung.  However, CT is 
preferable.  
 
Conventional CT and MRI: This guideline has defined measurability of lesions 
on CT scan based on the assumption that CT slice thickness is 5 mm or less.  If 
CT scans have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness.  MRI is also acceptable in 
certain situations (e.g. for body scans), but NOT lung.   
 


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Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and 
temporal resolution; however, there are many image acquisition variables 
involved in MRI, which greatly impact image quality, lesion conspicuity, and 
measurement.  Furthermore, the availability of MRI is variable globally.  As 
with CT, if an MRI is performed, the technical specifications of the scanning 
sequences used should be optimized for the evaluation of the type and site of 
disease.  Furthermore, as with CT, the modality used at follow-up should be the 
same as was used at baseline, and the lesions should be measured/assessed on 
the same pulse sequence.  It is beyond the scope of the RECIST guidelines to 
prescribe specific MRI pulse sequence parameters for all scanners, body parts, 
and diseases.  Ideally, subsequent image acquisitions should use the same type 
of scanner and follow the baseline imaging protocol as closely as possible.  If 
possible, body scans should be performed with breath-hold scanning techniques. 
 
PET-CT: At present, the low dose or attenuation correction CT portion of a 
combined PET-CT is not always of optimal diagnostic CT quality for use with 
RECIST measurements.  PET-CT scans are not always done with oral and IV 
contrast.  In addition, the PET portion of the CT introduces additional data 
which may bias an investigator if it is not routinely or serially performed.  For 
these reasons, the GOG will not allow PET-CT use for RECIST 1.1 
response criteria. 
 
FDG-PET:  While FDG-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of FDG-PET scanning to 
complement CT scanning in assessment of progression (particularly possible 
“new” disease).  New lesions on the basis of FDG-PET imaging can be 
identified according to the following algorithm:  
a. 
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is 
a sign of PD based on a new lesion. 
b. 
No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the 
positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD.  If the positive FDG-PET at follow-up is 
not confirmed as a new site of disease on CT, additional follow-up CT  
scans are needed to determine if there is truly progression occurring at 
that site (if so, the date of PD will be the date of the initial abnormal 
FDG-PET scan).  If the positive FDG-PET at follow-up corresponds to a 
pre-existing site of disease on CT that is not progressing on the basis of 
the anatomic images, this is not PD. 
 
 Note:  A “positive” FDG-PET scan lesion means one that is FDG avid with an 
uptake greater than twice that of the surrounding tissue on the attenuation 
corrected image. 
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not 
be used as a method of measurement.  Ultrasound examinations cannot be 
reproduced in their entirety for independent review at a later date and, because 
they are operator dependent, it cannot be guaranteed that the same technique and 
measurements will be taken from one assessment to the next.  If new lesions are 


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identified by ultrasound in the course of the study, confirmation by CT or MRI 
is advised.  If there is concern about radiation exposure at CT, MRI may be used 
instead of CT in selected instances. 
 
Endoscopy, Laparoscopy: The utilization of these techniques for objective tumor 
evaluation is not advised.  However, such techniques may be useful to confirm 
complete pathological response when biopsies are obtained or to determine 
relapse in trials where recurrence following complete response (CR) or surgical 
resection is an endpoint. 
 
CA-125 (Ovarian, fallopian tube and primary peritoneal cancer trials): CA125  
cannot be used to assess response or progression in this study.  If CA125 is 
initially above the upper normal limit, it must normalize for a patient to be 
considered in complete clinical response.  Specific guidelines for CA-125 
response (in recurrent ovarian cancer) have been published [JNCI 96:487-488, 
2004].    In addition, the Gynecologic Cancer Intergroup has developed CA-125 
progression criteria that are to be integrated with objective tumor assessment for 
use only in first-line trials in ovarian cancer [JNCI 92:1534-1535, 2000]. 
 
Cytology, Histology: These techniques can be used to differentiate between 
partial responses (PR) and complete responses (CR) in rare cases, e.g., residual 
lesions in tumor types, such as germ cell tumors, where known residual benign 
tumors can remain. 
 
 
It is mandatory to obtain cytological confirmation of the neoplastic origin of any 
effusion that appears or worsens during treatment when measurable disease has 
met criteria for response or stable disease.  This confirmation is necessary to 
differentiate response or stable disease versus progressive disease, as an effusion 
may be a side effect of the treatment. 
 
 
 
8.13 
Response Criteria 
 
 
Determination of response should take into consideration all target (See 8.131) 
and non-target lesions (See 8.132) and, if appropriate, biomarkers (See 8.133). 
 
 
 
 
8.131  
Evaluation of Target Lesions 
 
Complete Response (CR): Disappearance of all target lesions.  Any 
pathological lymph nodes (whether target or non-target) must have 
reduction in short axis to <10 mm. 
 
 
 
 
 
 
 
 
Partial Response (PR): At least a 30% decrease in the sum of the 
diameters of target lesions, taking as reference the baseline sum 
diameters. 
 
Progressive Disease (PD): At least a 20% increase in the sum of the 
diameters of target lesions, taking as reference the smallest sum on 
study (this includes the baseline sum if that is the smallest on study).  


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In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm.  (Note:  the 
appearance of one or more new lesions is also considered 
progressions). 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR 
nor sufficient increase to qualify for PD, taking as reference the 
smallest sum diameters while on study. 
 
 
 
 
8.132  
Evaluation of Non-Target Lesions 
 
Complete Response (CR): Disappearance of all non-target lesions. 
All lymph nodes must be non-pathological in size (<10 mm short 
axis). 
 
Note:  If CA-25 is initially above the upper normal limit, it must 
normalize for a patient to be considered in complete clinical 
response. 
 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) 
Progressive Disease (PD): Appearance of one or more new lesions 
and/or unequivocal progression of existing non-target lesions.  
Unequivocal progression should not normally trump target lesion 
status.  It must be representative of overall disease status change, not 
a single lesion increase. 
 
Not evaluable (NE):  When at least one non-target lesion is not 
evaluated at a particular time point. 
 
Although a clear progression of only “non-target” lesions is 
exceptional, the opinion of the treating physician should prevail in 
such circumstances, and the progression status should be confirmed 
at a later time by the review panel (or Principal Investigator). 
 
8.133 
Evaluation of Biomarkers 
 
If serum CA-125 is initially above the upper normal limit, it must 
normalize for a patient to be considered in complete clinical 
response. 
 
Progression cannot be based upon biomarkers, such as serum CA-
125, for this study. 
  
 
 
 
8.134  
Evaluation of Best Overall (unconfirmed) Response 
 
The best overall response is the best time point response recorded 
from the start of the treatment until disease progression/recurrence 
(taking as reference for progressive disease the smallest sum 


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recorded since baseline).  The patient's best response assignment will 
depend on the achievement of both measurement and confirmation 
criteria in some circumstances. 
 
Time Point Response for Patients with Measurable Disease at baseline (i.e., 
Target Disease) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time Point Response for Patients with only Non-Measurable Disease at 
baseline (i.e., Non-Target Disease) 
 
Non-Target 
Lesions 
Biomarker 
CA-125 
New 
Lesions* 
Time Point 
Response 
CR 
Within normal 
limits 
No 
CR 
CR 
Above normal 
limits 
No 
Non-CR/non-
PD* 
Non-CR/non-PD 
Any value 
No 
Non-CR/non-
PD* 
NE 
Any value 
No 
NE 
Unequivocal PD 
Any value 
Yes or No 
PD 
Any 
Any value 
Yes 
PD 
*See RECIST 1.1 manuscript for further details on what is evidence of a new lesion  
**  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target 
disease since SD is increasingly used as an endpoint for assessment of 
efficacy in some trials so to assign this category when no lesions can be 
measured is not advised 
 
8.135 Best Overall Confirmed Response  
Target 
Lesions 
Non-Target 
Lesions 
Biomarker 
CA-125 
New 
Lesions* 
Time Point  
Response 
CR 
CR 
Within 
normal 
limits 
No 
CR 
CR 
Non-CR/Non-PD 
Any value 
No 
PR 
CR 
NE 
Any value 
No 
PR 
PR 
Non-PD or NE 
Any value 
No 
PR 
SD 
Non-PD or NE 
Any value 
No 
SD 
NE 
Non-PD 
Any value 
No 
NE 
PD 
Any 
Any value 
Yes or 
No 
PD 
Any 
PD** 
Any value 
Yes or 
No 
PD 
Any 
Any 
Any value 
Yes 
PD 
 
*See RECIST 1.1 manuscript for further details on what is evidence of a new lesion  
 
** In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 


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Confirmation of CR and PR for determination of best overall 
response is required for studies with a primary endpoint that 
includes response. 
 
 
Confirmed CR and PR for best overall confirmed response 
 
Time Point Response 
First time point 
Time Point Response 
Subsequent time point 
BEST overall confirmed 
response 
CR 
CR 
CR 
CR 
PR 
SD, PD or PR* 
CR 
SD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD  
PR 
PD 
SD provided minimum criteria for SD 
duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD 
duration met, otherwise, NE 
NE 
NE 
NE 
 
*If a CR is truly met at first time point, then any disease seen at a 
subsequent time point, even disease meeting PR criteria relative to 
baseline, makes the disease PD at that point (since disease must have 
reappeared after CR).  However, sometimes ‘CR’ may be claimed when 
subsequent scans suggest small lesions were likely still present and in 
fact the patient had PR or SD, not CR at the first time point. Under these 
circumstances, the original CR should be changed to PR or SD and the 
best response is PR or SD.  
 
In non-randomized trials where response is part of the primary endpoint, 
confirmation of CR or PR is needed to deem either one the “best overall 
response.”   Responses (CR and PR) require confirmation at greater 
than or equal to 4 weeks from initial documentation. 
 
For this study, the minimum criteria for SD duration is 8 weeks. 
 
Patients with a global deterioration of health status requiring 
discontinuation of treatment or die without objective evidence of disease 
progression at that time should be reported to be off study treatment due 
to “symptomatic deterioration.”  Every effort should be made to 
document the objective progression even after discontinuation of 
treatment. 
  
 
 


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8.14 
Duration of Response 
 
Duration of overall response:  The duration of overall response is measured from 
the time measurement criteria are met for CR or PR (whichever is first recorded) 
until the first date that recurrent or progressive disease is objectively 
documented (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are 
first met for CR until the first date that progressive disease is objectively 
documented.  
 
Duration of stable disease:  Stable disease is measured from the start of the 
treatment until the criteria for progression are met, taking as reference the 
smallest measurements recorded since date of study entry, including the baseline 
measurements.  
 
 
8.15 
Progression-Free Survival 
 
Progression-Free Survival (PFS) is defined as the duration of time from study 
entry to time of progression or death, whichever occurs first. 
 
 
8.16 
Survival 
 
Survival is defined as the duration of time from study entry to time of death or 
the date of last contact. 
 
 
 
 
 
 
 


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9.0 
DURATION OF STUDY 
 
9.1 
Patients will receive therapy until disease progression or intolerable toxicity intervenes. 
The patient can refuse the study treatment at any time. 
 
9.2 
All patients will be treated (with completion of all required case report forms) until 
disease progression, initiation of a subsequent cancer treatment or study withdrawal.  
Patients will then be followed every three months for the first two years and then every 
six months for the next three years.  Patients will be monitored for delayed toxicity and 
survival for this 5-year period with Q forms submitted to the GOG Statistical and Data 
Center, unless consent is withdrawn.  Q forms will no longer be required if the study is 
terminated prior to the completion of the 5-year follow-up period.  
 
9.3  
A patient is considered off study therapy when the patient has progressed or died, a 
subsequent drug or therapy (directed at the disease) is initiated or all study therapy is 
discontinued. Report all treatment received on Form D2R and adverse events on Form T 
until the patient qualifies as being off study therapy. 


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10.0 
STUDY MONITORING & REPORTING PROCEDURE 
 
 
10.1 
ADVERSE EVENT REPORTING FOR AN INVESTIGATIONAL AGENT (CTEP 
IND) 
   
10.11 Definition of Adverse Events (AE) 
 
Adverse event (21 CFR 312.32(a)):  Any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug 
related. 
 
The descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized 
for AE reporting. All appropriate treatment areas should have access to a copy 
of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be 
downloaded from the CTEP web site (http://ctep.cancer.gov). The CTCAE v4.0 
Manual is also available on the GOG member web site (http://www.gog.org 
under MANUALS). 
 
10.12 Reporting Expedited Adverse Events 
 
 
Depending on the phase of the study, use of investigational agents, and role of 
the pharmaceutical sponsor, an expedited AE report may need to reach multiple 
destinations.  For patients participating on a GOG trial, all expedited AE reports 
should be submitted by using the CTEP automated system for expedited 
reporting (AdEERS).  All AdEERS submissions are reviewed by GOG before 
final submission to CTEP.  Submitting a report through AdEERS serves as 
notification to GOG, and satisfies the GOG requirements for expedited AE 
reporting. All AdEERS reports will be immediately directed to the Study Chair 
for further action. 
 
 
The requirement for timely reporting of AEs to the study sponsor is specified in 
the Statement of Investigator, Form FDA-1572.  In signing the FDA-1572, the 
investigator assumes the responsibility for reporting AEs to the NCI.  In 
compliance with FDA regulations, as contained in 21 CFR 312.64, AEs should 
be reported by the investigator. 
 
 
 
10.13 Late Phase 2 and Phase 3 Studies:  Expedited Reporting Requirements for 
Adverse Events that Occur on Studies under a CTEP IND/IDE within 30 Days 
of the Last Administration of the Investigational Agent/Intervention1, 2 
 
 
 
 
 
 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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Late Phase 2 and Phase 3 Studies:  Expedited Reporting Requirements for Adverse Events that Occur on 
Studies under a CTEP IND/IDE within 30 Days of the Last Administration of the Investigational 
Agent/Intervention 1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not they are 
considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 An adverse event is considered serious if it results in ANY of the following outcomes:   
1) Death 
2) A life-threatening adverse event  
3) An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 hours  
4) A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) A congenital anomaly/birth defect.  
6) Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. (FDA, 21 CFR 312.32; ICH 
E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via AdEERS 
within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 
Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
7 Calendar Days 
24-Hour 3 Calendar Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
7 Calendar Days 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in the Specific 
Protocol Exceptions to Expedited Reporting (SPEER) portion of the CAEPR 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” - The AE must initially be reported via AdEERS within 24 hours of learning of 
the AE, followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” - A complete expedited report on the AE must be submitted within 7 calendar days of 
learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• 
All Grade 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• 
Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• 
Grade 3 adverse events 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered.  Footnote “1” above 
applies after this reporting period. 


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Additional Instructions or Exceptions to AdEERS Expedited Reporting Requirements: 
 
• Reference the SPEER (Specific Protocol Exceptions to Expedited Report) for the subset of AEs 
that are protocol specific exceptions to expedited reporting via AdEERS.  Report AEs on the 
SPEER ONLY IF they exceed the grade noted in parentheses next to the AE in the SPEER.  If 
the CAEPR for a protocol agent is part of a combination protocol using multiple investigational 
agents and has an AE listed on different SPEERs, use the lower of the grades to determine if 
expedited reporting is required.  For questions or comments regarding the SPEER or CAEPR, 
please contact the AdEERS MD Help Desk at adeersmd@tech-res.com. 
 
10.14 Procedures for Expedited Adverse Event Reporting: 
 
10.141 AdEERS Expedited Reports: Expedited reports are to be submitted using 
AdEERS available at http://ctep.cancer.gov. The CTEP, NCI Guidelines: 
Adverse Event Reporting Requirements for expedited adverse event 
reporting requirements are also available at this site.  
 
 
AML/MDS events must be reported via AdEERS (in addition to  routine 
AE reporting mechanisms). In CTCAE v4.0, the event(s) may be 
reported as either: 1) Leukemia secondary to oncology chemotherapy, 2) 
Myelodysplastic syndrome, or 3) Treatment related secondary 
malignancy. Any malignancy possibly related to cancer treatment 
(including AML/MDS) should also be reported via the routine reporting 
mechanisms outlined in each protocol. (07/09/2012) 
 
 
In the rare event when Internet connectivity is disrupted a 24-hour 
notification is to be made to NCI by telephone at: 301-897-7497. An 
electronic report MUST be submitted immediately upon re-establishment 
of internet connection. Please note that all paper AdEERS forms have 
been removed from the CTEP website and will NO LONGER be 
accepted. 
  
 
 
 
 


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10.2 
GOG DATA MANAGEMENT FORMS 
The following forms must be completed and submitted to the GOG Statistical and Data 
Center (SDC) in accordance with the schedule below.  All forms except the BDR form,  
Pathology Report and BRCA Report(s) must be submitted via the SDC Electronic Data 
Entry System (SEDES) which is available through the GOG website 
(www.gogstats.org).  The BDR Form should be submitted via mail.  The GOG 
Uploader Application in SEDES is an alternate method for submitting pathology 
reports, BDR form and BRCA Report(s) to the GOG SDC. 
 
Form 
Due within 
Copies
* 
Comments 
Weeks 
Event 
Specimen Consent Application 
1 
Registration 
N/A 
Complete online 
Form R (Registration Form) 
 
2 
Registration 
1 
Mandatory Submission 
via SEDES 
Form OHR (Recurrent 
Gynecologic Cancer-On Study 
History Form) 
2 
Registration 
1 
Mandatory Submission 
via SEDES  
Form DR (Pre-Treatment 
Summary Form) 
4 
Registration 
1 
Mandatory Submission 
via SEDES  
Form BDR (Pre-Treatment Body 
Diagram Form) 
4 
Registration 
2 
Submit to SDC via postal 
mail or via report 
uploader in SEDES 
Form D2M (Solid Tumor 
Evaluation Form) 
4 
Registration 
1 
Mandatory Submission 
via SEDES  
Primary disease:** 
 
Pathology Report 
 
Recurrent or Persistent Disease:** 
Pathology Report (only if 
histologically documented)  
 
 
6 
 
 
6 
 
 
 
Registration 
 
 
Registration 
 
 
 
1 
 
 
1 
 
 
 
Submit to SDC via postal 
mail or via report 
uploader in SEDES 
 
 
Genetic Test Report (e.g., 
BRCAnalysis Report [actual report 
is required])*** (07/09/2012) 
6 
Registration 
2 
Submit to SDC via postal 
mail or via report 
uploader in SEDES 
 
BRCAnalysis Rearrangement 
(BART) Report (actual report, if 
performed)*** (07/09/2012) 
6 
Registration  
2 
Submit to SDC via postal 
mail or via report 
uploader in SEDES 
 
Form BMR (CA-125 reporting) 
(Biomarker Reporting Form) 
2 
Registration and 
completion of each cycle 
of therapy and disease 
assessment 
1 
Submit via SEDES 
Form D2R (Cycle Dose Drug 
Form) 
 
2 
Completion of each cycle 
of therapy 
1 
Mandatory Submission 
via SEDES  
Form D2M (Solid Tumor 
Evaluation Form) 
2 
Clinical response 
assessment 
1 
Mandatory Submission 
via SEDES  
Form T (Common Toxicity 
2 
Beginning of each 
1 
Mandatory Submission 


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Reporting Form) 
subsequent cycle 
via SEDES  
Form SP-FR01-0280 
Pre-Rx FFPE Recurrent EOC, FT, 
PPC 
8 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-FM01-0280 (optional) 
Pre-Rx FFPE Metastatic Tumor 
8 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-FP01-0280 (optional) 
Pre-Rx FFPE Primary EOC, FT, 
PPC 
8 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-RR01-0280 
Pre-Rx Frozen Recurrent EOC, FT, 
PPC 
2 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-RM01-0280 (optional) 
Pre-Rx Frozen Metastatic Tumor 
2 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-RP01-0280 (optional) 
Pre-Rx Frozen Primary EOC, FT, 
PPC 
2 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-SB01-0280 
Pre-Rx Serum 
2 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-WB01-0280 
Whole Blood for DNA Extraction 
32 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-FR02-0280 (optional) 
Post-Rx FFPE EOC, FT, PPC 
Biopsy or FNA 
32 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form SP-PF01-0280 (optional) 
Post-Rx FFPE Cell Pellet from 
Peritoneal Fluid 
32 
Registration 
N/A 
Mandatory Submission 
via SEDES†  
Form Q0 (Treatment Completion 
Form) 
 
2 
Completion of study Rx 
and change in Rx 
1 
Mandatory Submission 
via SEDES  
Form Q (Follow-up Form) 
 
 
2 
Disease progression; 
death; normal follow-up 
1 
Mandatory Submission 
via SEDES quarterly for 
2 years, semi-annually for 
3 more years 
* 
The number of required copies including the original form which must be sent to the Statistical 
and Data Center. 
** 
Pathology slides for Central Pathology Committee Review are not required on this study.   
*** Patients enrolled on this trial are required to have a known germline mutation in BRCA1 or BRCA2. 
Submission of the reports detailing this testing is required.  The following is the usual method for BRCA 
testing: If the patient is of Ashkenazi Jewish/Eastern European Jewish descent, testing begins with 
Multisite3 BRCAnalysis, continuing on to (“Reflex to”) Comprehensive BRCAnalysis if negative. Testing 
of non-Ashkenazi patients starts with Comprehensive BRCAnalysis.  Patients who are negative for the 
above testing can have BRCAnalysis Rearrangement Testing (BART).  Genetic counseling is strongly 
recommended before and after BRCA1/2 testing.  
† 
Form SP must be submitted regardless of whether the specimen is submitted for research. 
 
This study will be monitored by the Complete Clinical Data Update System (CDUS) version 3.0. 
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are due 
January 31, April 30, July 31 and October 31. 


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11.0     STATISTICAL CONSIDERATIONS 
 
The primary objective of this study is to assess the efficacy of the study agent in patients with 
recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer who carry a 
germline BRCA1 or BRCA2 mutation.  The primary measures of efficacy will be objective 
response. 
 
11.1 
This is a Phase II study and no randomization is involved, however, patient registration 
will be accomplished in the usual fashion. 
 
11.11 Primary Endpoints: 
 
11.111 The frequency of patients who have objective tumor response. 
 
11.112 Frequency and severity of adverse effects as assessed by CTCAE v4.0. 
 
11.12 Secondary Endpoints: 
 
11.121 Duration of progression-free survival and overall survival. 
 
11.122 The proportion of patients who survive progression-free for at least 6 
 
months. 
 
11.13 Translational Research and Exploratory Endpoints: 
 
11.131 SNPs with DNA repair genes, tumor response, PFS, OS, and patient 
demographics (e.g. age, race, tumor grade). 
 
11.132 BRCA mutation in primary tumor tissue. 
 
11.2 
The anticipated annual accrual is 50 patients. 
 
11.21 The anticipated period of active accrual for the first stage is 5.5 months. 
 
11.22 The anticipated period of active accrual for the second stage is 6.0 months. 
 
11.3 
The study plan is a single arm, 2-stage phase II clinical trial. 
 
End point and design selection 
The agent studied in this particular protocol is expected to reduce tumor burden, 
producing objective responses.  
 
The guiding principle in selecting the design for this study is to limit the number of 
patients treated with clinically ineffective therapies; yet tend to estimate efficacy with 
reasonable precision for those agents that are clinically active.  Strict adherence to a 
two-stage sampling design with ‘optimal’ early stopping rules is not practical because 
the accrual is complicated by the logistics of managing a multi-center phase II study.  
Instead, flexible stopping rules are used that tend to maximize the probability of 


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rejecting the treatment when the agent is indeed not active.  When the targeted sample 
size is attained, those patients who have already been approached will be permitted to 
register. 
 
Historical Data and Design Parameters 
There is not a substantial historical control available that examines the proportion of 
patients responding or PFS who have germline BRCA1 or BRCA2 mutations.   Audeh 
et al.2 studied a PARP inhibitor, olaparib, in a phase II study with recurrent ovarian 
cancer patients at two dose levels: 100 mg BID and 400 mg BID.  The first cohort of 33 
patients enrolled on the study evaluated the dose at 400 mg.  Another cohort of 24 
patients was enrolled at the 100 mg dose.  11 of 33 (33%; 95% CI 20-51%) evaluable 
patients responded to the drug at the 400 mg dose whereas 3 of 24 (13%; 95% CI 4-
31%) responded to the 100 mg dose.  Approximately 15 of 33 (45%) patients remained 
progression-free at 6 months with the 400 mg dose, and 5 of 24 (21%) remained 
progression-free at 6 months with the 100 mg dose.  Another internal ancillary study of 
patients with high grade serous cancer, which are believed to have a higher proportion 
of patients with BRCA mutations, concluded that the proportion of patients responding 
or PFS at 6 months was approximately the same as the general ovarian cancer 
population (at least for inactive agents).  Based on this data, we propose the following 
null hypothesis for uninteresting activity: 
H0: πr≤ 0.10  
 
To evaluate this hypothesis in a two-stage design, a method provided by Chen and Ng 
will be used to decide whether there are sufficient numbers of patients with objective 
responses to continue study in a second stage (at the interim analysis) or deem the drug 
worthy of further investigation in a randomized study (at the end of stage 2).17  In 
particular, the following decision rule will be applied where Xr(1) is the number of 
patients with objective tumor responses (partial or complete) after the first stage, Xr is 
the cumulative number of patients with responses after stage 2, Cr(1) is the critical value 
for Xr(1), and Cr is the critical value for Xr: 
 
Decision Rule: If Xr(1)> Cr(1) after the first stage, then the study will open to a second 
stage of accrual to further evaluate the activity of the drug.  If Xr > Cr after the second 
stage and clinical judgment indicates, then the agent will be deemed clinically 
interesting and worthy of further investigation. 
 
The targeted accrual for the first stage will be 23 eligible and evaluable patients but 
permitted to range from 19 to 26 for administrative reasons.  The cumulative targeted 
accrual for the second stage will be 48 eligible and evaluable patients but permitted to 
range from 44 to 51 for administrative reasons.  Critical values for each stage are 
provided below: 
 
Table 11.1: Critical values for the number of 
patients with objective responses. 
Stage 1 
n(1)* 19 20 21 22 23 24 25 26 
Cr(1) 
2 
2 
2 
2 
2 
2 
2 
3 


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* n(1) is the sample size for the first stage of     
  accrual. 
 
 Table 11.2: Critical values for the number of patients with objective 
responses. 
Stage 2 
 
n* 44 45 46 47 48 49 50 51 
Cr 
6 
6 
7 
7 
7 
7 
7 
7 
* n is the cumulative sample size after the second stage of accrual. 
 
This study has 10% alpha and 90% power when the probability of response is 25%. 
 
 
 
 
Figure 11.1: Average Probability of Early Termination (APET; solid line) and Average 
Total Probability of Rejecting the Treatment (ATPRT; dashed line) as a function of the 
true probability of response. 
 
11.4 
Evaluability for efficacy and toxicity 
Only those patients who are deemed "ineligible" or who receive no therapy will be 
eliminated from the analysis.  All patients who receive any therapy will be evaluated for 
both treatment efficacy and toxicity.  While on occasion, circumstances may prevent the 
determination of treatment efficacy, such patients will be included in the analysis and 
labeled as "indeterminate".  This category will be listed and be reflected in the 
calculation of the response rate or proportion surviving progression-free for at least 6 
months. 
 
11.5 
Data Safety and Monitoring 
Data sheets from studies on this protocol will be reviewed before each semi-annual 
meeting and will also be reviewed by the Study Chairperson in conjunction with the 
Statistical and Data Center.  In some instances, because of unexpectedly severe toxicity, 
APET/ATPRT
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Probability of Response
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
0.22
0.24
0.26
0.28
0.30


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the Statistical and Data Center may elect, after consultation with the Study Chairperson 
and the Medical Oncology Committee, to recommend early closure of a study. 
 
The frequency and severity of all toxicities are tabulated from submitted case report 
forms and summarized for review by the study chairperson, Developmental 
Therapeutics Committee, and GOG Safety Review Committee (SRC) in conjunction 
with each semi-annual GOG meeting. For studies sponsored by the Cancer Therapy 
Evaluation Program (CTEP) of the National Cancer Institute (NCI), standardized 
toxicity reports are also submitted to the drug and disease monitors at the 
Investigational Drug Branch (IDB) and Clinical Investigation Branch (CIB).  The initial 
overall review of toxicity is usually performed after completion of the first stage of 
accrual, at which point accrual is generally suspended pending formal analysis of 
response and toxicity. 
 
All serious and/or unexpected events are communicated to the Study Chair, sponsor, 
and regulatory agencies as mandated in the protocol. These reports are reviewed by the 
Study Chair (or designated co-chair) for consideration of investigator notification, 
amendment, or immediate study suspension.  All participating institutions will then 
receive notification of the toxicities and reason for study suspension.   Under these 
circumstances, accrual cannot be re-activated until the study is reviewed by the GOG 
SRC.  However, patients currently receiving treatment may continue to receive 
treatment in accordance protocol guidelines at the discretion of their physicians, unless 
directed otherwise. 
 
11.6 
Secondary Endpoints and Exploratory Analyses 
 
Overall survival and progression-free survival will be characterized with Kaplan-Meier 
plots and estimates of the median time until death or progression. 
 
If the clinical trial goes to the second stage and there is sufficient variability in the 
SNPs, then patients can be categorized by the nature of their SNPs and assessed for 
prognostic value through survival analysis (e.g. log-rank tests and Cox proportional 
hazards modeling).  These analyses will be conducted as hypothesis generating rather 
than hypothesis testing.  If the variability in SNPs is relatively low, assessment of 
prognostic value can be conducted with odds ratios of patients responding or surviving 
progression-free for at least 6 months.  These techniques will use exact methods such as 
Fisher’s Exact Test.  In addition, associations with demographic characteristics, for 
example race, cell type, and tumor grade, will be examined with methods that use 
categorical data (e.g. exact Chi-square tests), and tables may be provided for those 
associations deemed interesting. 
 
BRCA mutational status will be tabulated against the germline mutation to see what 
proportion of patients have a mutation reversal within the tumor and whether such 
reversals can explain resistance to the regimen under study.   
 
 


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11.7 
Accrual Targets 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
0 
+ 
 
= 
0 
Not Hispanic or Latino 
51 
+ 
 
= 
51 
Ethnic Category: Total of all subjects 
51 
+ 
 
 
= 
51 
Racial Category 
 
American Indian or Alaskan Native 
0 
+ 
 
= 
0 
Asian 
1 
+ 
 
= 
1 
Black or African American 
2 
+ 
 
= 
2 
Native Hawaiian or other Pacific Islander 
0 
+ 
 
= 
0 
White 
48 
+ 
 
= 
48 
Racial Category: Total of all subjects 
51 
+ 
 
 
= 
51 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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12.0 
BIBLIOGRAPHY 
 
1. Fong PC, Boss DS, Yap TA, et al.  Inhibition of poly(ADP-Ribose) polymerase in tumors 
from BRCA mutation carriers.  N Engl J Med 2009;361:123-34. 
 
2. Audeh MW, Carmichael J, Penson RT, et al.  Oral poly(ADP-ribose) polymerase inhibitor 
olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer:  a 
proof-of-concept trial.  Lancet 2010;376:245-51.  
 
3. Tutt A, Robson M, Garber JE, et al.  Oral poly(ADP-ribose) polymerase inhibitor olaparib 
in patients with BRCA1 or BRCA2 mutations and advanced breast cancer:  a proof-of-
concept trial.  Lancet 2010;376:235-44. 
 
4. Fong PC, Yap TA, Boss DS, et al.  Poly(ADP)-Ribose polymerase inhibition:  frequent 
durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.  J 
Clin Oncol 2010;28:251219. 
 
5. Sakai W, Swisher EM, Jacquemont C, et al.  Functional restoration of BRCA2 protein by 
secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma.  Cancer Res 
2009;69:6381-6386. 
 
6. Sakai W, Swisher EM, Karlan BY, et al.  Secondary mutations as a mechanism of cisplatin 
resistance in BRCA2-mutated cancers.  Nature 2008;451:1116-1120. 
 
7. Edwards SL, Brough R, Lord CJ, et al.  Resistance to therapy caused by intragenic deletion 
in BRCA2.  Nature 2008;451:1111-1115. 
 
8. Swisher EM, Sakai W, Karlan BY, et al.  Secondary BRCA1 mutations in BRCA-1 mutated 
ovarian carcinomas with platinum resistance.  Cancer Res 2008;68:2581-2586. 
 
9. Norquist B, Wurz KA, Pennil CC, et al.  Secondary somatic mutations restoring BRCA 1/2 
predict chemotherapy resistance in hereditary ovarian carcinoma.  J Clin Oncol 
2011;29:3008-3015. 
 
10. Gelmon KA, Tischkowitz M, Mackay H, 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 
Sep;12(9):852-61. 
 
11. Kaye SB, Lubinski J, Matulonis U, et al.  Phase II, open-label, randomized, multicenter 
study comparing the efficacy and safety of olaparib, a Poly (ADP-Ribose) Polymerase 
inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 
mutations and recurrent ovarian cancer.  J Clin Oncol 2012;30:372-379. (07/09/2012) 
 
12. Ledermann J, Harter P, Gourley C, et al.  Olaparib maintenance therapy in platinum-
sensitive relapsed ovarian cancer.  N Engl J Med 2012;366:1382-92. (07/09/2012) 
 


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13. Molife LR, Forster MD, Krebs M, et al.  A phase I study to determine the comparative 
bioavailability of two different oral formulations of the PARP inhibitor, olaparib 
(AZD2281), in patients with advanced solid tumors.  J Clin Oncol 2010;28:suppl; abstr 
2599. 
 
14. Liu X, Palma J, Kinders R, et al. An enzyme-linked immunosorbent Poly (ADP-ribose) 
polymerase (PARP) biomarker assay for clinical trials of PARP inhibitors. Analytical Chem 
2008;381:240-247. 
 
15. Palma J, Rodriguez L, Bontcheva-Diaz V, et al.  The PARP inhibitor, ABT-888, potentiates 
temozolomide: correlation with drug levels and reduction in PARP activity in vivo. 
Anticancer Res 2009;28:2625-2635. 
 
16. Kummar S, Kinders R, Gutierrez ME, et al.  Phase 0 clinical trial of the poly (ADP-ribose) 
polymerase inhibitor ABT-888 in patients with advanced malignancies.  J Clin Oncol 
2009;27:2705-11. 
 
17. Chen TT and NG TH.  Optimal flexible designs in phase II clinical trials.  Statistics in 
Medicine (17) 2301-2312, 1998. 
 
 
 
 
 


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APPENDIX I  
 
NCI/ DCTD Standard Language to Be Incorporated into All Protocols Involving Agent(s) Covered 
by a Clinical Trials Agreement (CTA) a Cooperative Research and Development Agreement 
(CRADA)or a Clinical Supply Agreement, hereinafter referred to as Collaborative Agreement: 
 
 
The agent(s) supplied by CTEP, DCTD, NCI used in this protocol is/are provided to the 
NCI under a Collaborative Agreement (CRADA, CTA, CSA) between the Pharmaceutical 
Company(ies) (hereinafter referred to as “Collaborator(s)”) and the NCI Division of Cancer 
Treatment and Diagnosis.  Therefore, the following obligations/guidelines, in addition to 
the provisions in the “Intellectual Property Option to Collaborator” 
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm) ontained within 
the terms of award, apply to the use of the Agent(s) in this study: 
 
1.   Agent(s) may not be used for any purpose outside the scope of this protocol, nor can 
Agent(s) be transferred or licensed to any party not participating in the clinical study.  
Collaborator(s) data for Agent(s) are confidential and proprietary to Collaborator(s) and 
shall be maintained as such by the investigators.  The protocol documents for studies 
utilizing Agents contain confidential information and should not be shared or 
distributed without the permission of the NCI.  If a copy of this protocol is requested by 
a patient or patient’s family member participating on the study, the individual should 
sign a confidentiality agreement.  A suitable model agreement can be downloaded from: 
http://ctep.cancer.gov. 
 
2.   For a clinical protocol where there is an investigational Agent used in combination with 
(an)other Agent(s), each the subject of different Collaborative Agreements, the access 
to and use of data by each Collaborator shall be as follows (data pertaining to such 
combination use shall hereinafter be referred to as "Multi-Party Data”): 
 
a.  NCI will provide all Collaborators with prior written notice regarding the existence 
and nature of any agreements governing their collaboration with NCI, the design of 
the proposed combination protocol, and the existence of any obligations that would 
tend to restrict NCI's participation in the proposed combination protocol. 
 
b.  Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical 
trial by any other Collaborator solely to the extent necessary to allow said other 
Collaborator to develop, obtain regulatory approval or commercialize its own 
Agent. 
 
c.  Any Collaborator having the right to use the Multi-Party Data from these trials must 
agree in writing prior to the commencement of the trials that it will use the Multi-
Party Data solely for development, regulatory approval, and commercialization of 
its own Agent. 
 
3.   Clinical Trial Data and Results and Raw Data developed under a Collaborative 
Agreement will be made available to Collaborator(s), the NCI, and the FDA, as 
appropriate and unless additional disclosure is required by law or court order as 


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described in the IP Option to Collaborator 
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm).  
Additionally, all Clinical Data and Results and Raw Data will be collected, used and 
disclosed consistent with all applicable federal statutes and regulations for the 
protection of human subjects, including, if applicable, the Standards for Privacy of 
Individually Identifiable Health Information set forth in 45 C.F.R. Part 164. 
 
4.   When a Collaborator wishes to initiate a data request, the request should first be sent to 
the NCI, who will then notify the appropriate investigators (Group Chair for 
Cooperative Group studies, or PI for other studies) of Collaborator's wish to contact 
them. 
 
5.   Any data provided to Collaborator(s) for Phase 3 studies must be in accordance with the 
guidelines and policies of the responsible Data Monitoring Committee (DMC), if there 
is a DMC for this clinical trial. 
 
6.   Any manuscripts reporting the results of this clinical trial must be provided to CTEP by 
the Group office for Cooperative Group studies or by the principal investigator for non-
Cooperative Group studies for immediate delivery to Collaborator(s) for advisory 
review and comment prior to submission for publication.  Collaborator(s) will have 30 
days from the date of receipt for review.  Collaborator shall have the right to request 
that publication be delayed for up to an additional 30 days in order to ensure that 
Collaborator’s confidential and proprietary data, in addition to Collaborator(s)’s 
intellectual property rights, are protected.  Copies of abstracts must be provided to 
CTEP for forwarding to Collaborator(s) for courtesy review as soon as possible and 
preferably at least three (3) days prior to submission, but in any case, prior to 
presentation at the meeting or publication in the proceedings.  Press releases and other 
media presentations must also be forwarded to CTEP prior to release.  Copies of any 
manuscript, abstract and/or press release/ media presentation should be sent to: 
 
Email:  ncicteppubs@mail.nih.gov  
 
The Regulatory Affairs Branch will then distribute them to Collaborator(s).  No 
publication, manuscript or other form of public disclosure shall contain any of 
Collaborator’s confidential/ proprietary information. 
 
 


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Appendix II  - GOG General Chemotherapy Guidelines 
 
 
• For 21 or 28 day cycles, a patient will be permitted to have a new cycle of 
chemotherapy delayed up to 7 days (without this being considered to be a protocol 
violation) for major life events (e.g., serious illness in a family member, major holiday, 
vacation which is unable to be re-scheduled).  Documentation to justify this decision 
should be provided. 
• It will be acceptable for individual chemotherapy doses to be delivered within a “24-
hour window before and after the protocol-defined date” for “Day 1” treatment of 21 or 
28 day cycles.  If the treatment due date is a Friday, and the patient cannot be treated on 
that Friday, then the window for treatment would include the Thursday (1 day earlier 
than due) through the Monday (day 3 past due). 
• For weekly regimens, it will be acceptable for individual chemotherapy doses to be 
delivered within a “24-hour window,” for example; “Day 8 chemotherapy” can be 
delivered on Day 7, Day 8, or Day 9 and “Day 15 chemotherapy” can be given on Day 
14, Day 15, or Day 16. 
• Chemotherapy doses can be “rounded” according to institutional standards without 
being considered a protocol violation (most institutions use a rule of approximately +/- 
5% of the calculated dose). 
• Chemotherapy doses are required to be recalculated if the patient has a weight change 
of greater than or equal to 10%.  Patients are permitted to have chemotherapy doses 
recalculated for <10% weight changes. 
 
 


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APPENDIX III - PATIENT PILL CALENDAR 
 
Patient Name: _________________________ 
Month/Date of first dose on calendar: ____________________ 
Patient Study ID______________________________ 
Visit Log is returned at: each visit 
  
 
This is a calendar on which you are to record the number of pills you take each day for 4 weeks.   You will get a 
new calendar for each 4-week cycle.  
• 
You should take your dose of Veliparib two times a day, about the same time every day. 
• 
The doses should be taken about 12 hours apart.   
• 
If you are more than 4 hours late in taking a dose, the dose should be skipped.  
• 
Pills may be taken with or without food, please swallow pills with about 8 ounces of water.   
• 
If you develop any side effects, please record side effects, the day they occurred and anything else you 
would like to tell the doctor in the space provided below the calendar.   
• 
If you are more than 4 hours late in taking a dose, the dose should be skipped.  Call your doctor’s office 
if you do not know what to do. 
• 
Bring any unused pills, pill bottles and your completed calendar to your next appointment.   
• 
Please record the date drug was taken in each box.   
 
Date:        
              
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
             
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
              
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                       
  
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                     
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
             
 
AM Time 
___ 
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
 Date:       
              
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
             
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
              
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                       
  
AM Time 
___ 
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
                     
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
Date: 
             
 
AM Time 
___ 
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
 Date:       
              
 
AM Time 
Date: 
             
 
AM Time 
Date: 
              
 
AM Time 
Date: 
                
 
AM Time 
Date: 
                       
  
AM Time 
Date: 
                     
 
AM Time 
Date: 
             
 
AM Time 


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___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
___   
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
___ 
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
 
 Date:       
             
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
             
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
              
 
AM Time 
___   
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
                
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
                       
  
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
                     
 
AM Time 
___  
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
Date: 
             
 
AM Time 
___ 
# of pills   
___ 
 
PM Time 
___ 
# of pills   
___ 
 
 
Side effects: 
 
 
__________________________________________________________________________________________
__________________________________________________________________________________________ 
__________________________________________________________________________________________ 
__________________________________________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
___________ 
 
SIGNATURE OF PATIENT 
 
 
 
 
 
 
DATE 
 
Note to staff: Please give patient a drug log at initial enrollment and prior to each cycle. 
 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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Appendix IV - Specimen Procedures 
 
Specimen Procedures 
 
I. 
Summary of Specimen Requirements 
 
Required Specimen 
(Specimen Code) 
Collection Time Point 
Ship To 
Pre-Treatment FFPE 
Recurrent Tumor (FR01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Prior to Veliparib treatment 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment FFPE 
Metastatic Tumor (FM01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Prior to Veliparib treatment 
(may be archival pre-
treatment) 
 
If FR01or FP01 cannot be 
submitted 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment FFPE Primary 
Tumor (FP01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged + 10 10µm 
uncharged) 
Archival pre-treatment 
 
If FR01 or FM01 cannot be 
submitted 
GOG Tissue Bank within 8 
weeks of registration1 
Pre-Treatment Frozen 
Recurrent Tumor (RR01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Prior to Veliparib treatment 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Frozen 
Metastatic Tumor (RM01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Prior to Veliparib treatment 
(may be archival pre-
treatment) 
 
If RR01or RP01 cannot be 
submitted 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Frozen Primary 
Tumor (RP01) 
1st Choice: Snap Frozen 
2nd Choice: OCT Embedded 
Archival pre-treatment 
 
If RR01 or RM01 cannot be 
submitted 
GOG Tissue Bank within 2 
weeks of registration1 
Pre-Treatment Serum (SB01) 
prepared from 7-10mL blood 
drawn into a plain red top tube 
Prior to Veliparib treatment 
GOG Tissue Bank within 2 
weeks of registration1 
Whole Blood (WB01) 
7-10mL drawn into purple top 
(EDTA) tube(s) 
Prior to or after initiating 
Veliparib treatment 
GOG Tissue Bank the day the 
blood is collected1 
Post-Treatment FFPE Biopsy 
Optional - Post-treatment, if 
GOG Tissue Bank within 32 


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or FNA (FR02) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged ; 10 10µm 
uncharged, if possible) 
patient has biopsy or FNA at 
time of progression 
weeks of registration1 
Post-Treatment FFPE Cell 
Pellet from Peritoneal Fluid 
(PF01) 
1st Choice: Block 
2nd Choice: Unstained Slides 
(10 5µm charged ; 10 10µm 
uncharged, if possible) 
Optional - Post-treatment at 
time of progression 
 
If FR02 cannot be submitted 
GOG Tissue Bank within 32 
weeks of registration1 
1 
GOG Tissue Bank / Protocol GOG-0280, Nationwide Children’s Hospital, 700 Children’s Drive, WA1340, Columbus, OH 
43205, Phone: (614) 722-2865, FAX: (614) 722-2897, Email: GOGBanc@nationwidechildrens.org  
 
II. 
Obtaining a GOG Bank ID 
 
Only one GOG Bank ID (# # # # - # # - G # # #) is assigned per patient. All specimens and 
accompanying paperwork must be labeled with this coded and confidential tracking number. A 
GOG Bank ID can be obtained online via the Tissue Bank Portal on the GOG website (under 
Tools on the Web Menu page). 
 
Obtain the patient study ID for all protocols with specimen requirements before requesting a 
GOG Bank ID from the Tissue Bank Portal.  
 
Please contact the User Support Department at the GOG Statistical and Data Center at 
support@gogstats.org or by phoning 716-845-7767 if you need assistance. 
 
III. 
Requesting Specimen Kits 
 
A. 
Ordering Specimen Kits 
 
Specimen kits may be ordered online via the Kit Management link on the GOG website 
(under Data Entry on the Web Menu page). 
 
Please contact the GOG Tissue Bank at GOGBank@nationwidechildrens.org or by 
phoning 866-GOG-BANC (866-464-2262) if you need assistance. 
 
Please plan ahead to allow time for kits to be shipped by ground transportation. 
 
B. 
Materials Provided in the Specimen Kits 
 
One specimen kit will be provided per patient for the collection and shipment of frozen 
specimens. Each kit will consist of: 
 
• 
single-chamber shipping container 
• 
five cryovials 
• 
one transfer pipettes 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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• 
one 15mL conical tubes 
• 
one piece of foil 
• 
one secondary shipping envelope(s) with absorbent material 
• 
one Tyvek envelope(s) 
• 
Dry ice label (UN1845) 
• 
Exempt Human Specimen sticker 
 
If there are supplies needed to satisfy the specimen requirements that are not provided in 
the kit (and are not available at your site), please contact the GOG Tissue Bank. 
 
C. 
Unused Materials and Specimen Kits 
 
Unused materials and specimen kits should be returned to the GOG Tissue Bank. 
Contact the bank if you have any questions about the return of unused materials. 
 
IV. 
Submitting Formalin-Fixed, Paraffin-Embedded Tumor 
 
A. 
Requirement 
 
If the patient gives permission for her tumor specimens to be used for this optional 
translational research component, then the participating institution is required to submit 
specimens as outlined in Section I. 
 
Every attempt should be made to provide FFPE blocks. 
 
If tumor blocks cannot be provided, please provide unstained slides – 10 5µm charged 
and 10 10µm uncharged. 
 
If FFPE biopsy or FNA blocks cannot be provided, please provide unstained slides - at 
least 10 5µm charged; if possible, also provide 10 10µm uncharged. 
 
The type of specimen (block or slides) should be specified on Form SP. 
 
B. 
Purpose 
 
DNA extracted from FFPE tumor will be used for genomic analysis. 
 
C. 
Time Points 
 
Pre-treatment FFPE tumor should be collected prior to Veliparib treatment. 
 
Recurrent tumor is the preferred specimen. If recurrent tumor cannot be submitted, 
submit metastatic tumor collected prior to Veliparib treatment (or archival metastatic 
tumor). If recurrent or metastatic tumor cannot be submitted, submit archival, pre-
treatment primary tumor. 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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Post-treatment FFPE biopsy or FNA should be collected post-Veliparib treatment, if the 
patient has a biopsy or FNA at the time of progression. 
 
D. 
Format for Labeling the Specimen 
 
Label the specimen with the GOG protocol number (GOG-0280), GOG Bank ID (# # # 
# - # # - G # # #), specimen code (FP01 for primary, FM01 for metastatic, FR01 for 
recurrent, FR02 for post-treatment biopsy or FNA), and collection date (mm/dd/yyyy). 
 
V. 
Submitting Frozen Tumor 
 
A. 
Requirement 
 
If the patient gives permission for her tumor specimens to be used for this optional 
translational research component, then the participating institution is required to submit 
specimens as outlined in Section I. 
 
Please submit at least 0.2 grams of frozen tissue. 
 
Every attempt should be made to provide snap frozen tissue; however, if snap frozen 
tissue cannot be provided, frozen tissue may be OCT-embedded. 
 
The type of specimen (snap frozen or OCT-embedded) should be specified on Form SP. 
 
B. 
Purpose 
 
DNA extracted from frozen tumor will be used for genomic analysis. 
 
C. 
Time Points 
 
Pre-treatment frozen tumor should be collected prior to Veliparib treatment. 
 
Recurrent tumor is the preferred specimen. If recurrent tumor cannot be submitted, 
submit metastatic tumor collected prior to Veliparib treatment (or archival metastatic 
tumor). If recurrent or metastatic tumor cannot be submitted, submit archival, pre-
treatment primary tumor. 
 
D. 
Format for Labeling the Specimen 
 
Label the specimen with the GOG protocol number (GOG-0280), GOG Bank ID (# # # 
# - # # - G # # #), specimen code (RP01 for primary, RM01 for metastatic, RR01 for 
recurrent), and collection date (mm/dd/yyyy). 
 
VI. 
Submitting Serum 
 
A. 
Requirement 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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If the patient gives permission for her blood specimens to be used for this optional translational 
research component, then the participating institution is required to submit specimens as outlined in 
Section I. 
 
B. 
Purpose 
 
Pre-treatment serum will be banked for future research. 
 
C. 
Time Points 
 
Serum should be collected at prior to Veliparib treatment. 
 
D. 
Format for Labeling the Specimen 
 
Label the specimen with the GOG protocol number (GOG-0280), GOG Bank ID (# # # # - # # - G # # 
#), specimen code (SB01), and collection date (mm/dd/yyyy). 
 
E. 
Instructions for Preparing the Specimen 
 
1.  
Label five screw-cap cryotubes as described above.  
 
2.  
Draw 7-10mL of blood into plain red top tube(s).  
 
3.  
Allow the blood to clot at room temperature for at least 30 minutes*. 
 
 
*If the clotted blood cannot be centrifuged immediately, it can be stored at 4°C 
(or in a bucket with ice) for up to 3 hours. 
 
4.  
Centrifuge the clotted blood to separate the serum (transparent, straw colored 
liquid) from the fibrin clot and blood cells. 
 
 
When the appropriate equipment is available, centrifuge blood at 3500g at 4°C 
for 10 minutes. Blood must be centrifuged at a minimum of 1000g at room 
temperature for 15 minutes* (the longer centrifugation time will help 
compensate for the slower speed). 
 
 
*Avoid centrifugation without refrigeration longer than 15 minutes as excess 
heat may damage the serum.  
 
5.  
Transfer the serum into a 15mL conical tube and gently mix. Quickly, evenly 
dispense (aliquot) the serum into the pre-labeled cryotubes and cap the tubes 
securely. 
 
6.  
Immediately freeze the serum in an upright position using an appropriate 
freezing/storage space (i.e., ultra cold ≤-70oC freezer, liquid nitrogen, or direct 
exposure with dry ice). Frozen serum specimens should be stored in an ultra 
cold freezing/storage space until the specimens can be shipped. 
 


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VII. 
Submitting Whole Blood 
 
A. 
Requirement 
 
If the patient gives permission for her blood specimens to be used for this optional translational 
research component, then the participating institution is required to submit specimens as outlined in 
Section I. 
 
B. 
Purpose 
 
DNA extracted from whole blood will be used for genomic analysis. 
 
C. 
Time Points 
 
Whole blood can be collected at any time prior to or after initiating Veliparib treatment. 
 
D. 
Format for Labeling the Specimen 
 
Label the specimen with the GOG protocol number (GOG-0280), GOG Bank ID (# # # # - # # - G # # 
#), specimen code (WB01), and collection date (mm/dd/yyyy). 
 
E. 
Instructions for Preparing the Specimen 
 
1.  
Label the purple top whole blood collection tube(s) (containing EDTA) as 
described above.  
 
2. 
Draw 7-10mL of blood into the labeled purple top tube(s).  
 
3.  
Mix the blood with the EDTA by gently inverting the tube 5-10 times. 
   
4. 
Ship the whole blood specimen to GOG Tissue Bank the day the specimen is 
collected*. Whole blood specimens should be stored at room temperature until 
the specimens can be shipped. 
 
 
* If the whole blood absolutely cannot be shipped the day it is collected, the tube 
may be placed in the refrigerator overnight. Please note that the blood was 
refrigerated overnight in the comment box on Form SP (item 15). 
 
VIII. Submitting Formalin-Fixed, Paraffin-Embedded Cell Pellet from Peritoneal Fluid 
 
A. 
Requirement 
 
If the patient gives permission for her peritoneal specimens to be used for this optional translational 
research component, then the participating institution is required to submit specimens as outlined in 
Section I. 
 
Every attempt should be made to provide FFPE cell pellet blocks. 
 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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If blocks cannot be provided, please provide unstained slides - at least 10 5µm charged; if possible, 
also provide 10 10µm uncharged. 
 
The type of specimen (block or slides) should be specified on Form SP. 
 
B. 
Purpose 
 
DNA extracted from FFPE cell pellets will be used for genomic analysis. 
 
C. 
Time Points 
 
Post-treatment FFPE cell pellets from peritoneal fluid should be collected post-Veliparib treatment at 
the time of progression, if a biopsy or FNA is not collected. 
 
D. 
Format for Labeling the Specimen 
Label the specimen with the GOG protocol number (GOG-0280), GOG Bank ID (# # # # - # # - G # # 
#), specimen code (PF01), and collection date (mm/dd/yyyy). 
 
IX. 
Submitting Form SP 
 
A. 
Form SP Requirements 
 
Form SP must be completed and submitted online to the GOG Statistical and Data Center (SDC) using 
the SDC Electronic Data Entry System (SEDES). Form SP must be submitted for each specimen 
required for the protocol regardless of the specimen submission status. Specific instructions for 
completing Form SP are available via SEDES by scrolling down to the SP Forms for the specific 
protocol. 
 
B. 
Instructions for Submitting Form SP Online 
 
Form SP must be submitted online using SEDES which is available on the GOG Web 
Menu under Registration/Data Entry. A copy of the completed form must also 
accompany each specimen shipped to the GOG Tissue Bank. Retain a printout of the 
completed form for your records. Form SP does not need to be sent to the GOG Tissue 
Bank when specimens are not collected. 
 
To access Form SP for online submission, log onto the GOG Web Menu and use 
SEDES to electronically enter Form SP data. Any questions about access or problems 
should be directed to the User Support Department at the GOG Statistical and Data 
Center at support@gogstats.org or by phoning 716-845-7767. 
 
X. 
Shipping Specimens 
 
A. 
FFPE 
 
FFPE specimens should be shipped using your own container at your own expense to: 
 
GOG Tissue Bank / Protocol GOG-0280 


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Nationwide Children’s Hospital 
700 Children’s Dr, WA1340 
Columbus, OH 43205 
Phone: (614) 722-2865 
FAX: (614) 722-2897 
Email: GOGBank@nationwidechildrens.org  
 
B. 
Whole Blood 
 
All whole blood specimens should be shipped to the GOG Tissue Bank using your own 
container and a pre-paid FedEx shipping label: 
 
GOG Tissue Bank / Protocol GOG-0280 
Nationwide Children’s Hospital 
700 Children’s Dr, WA1340 
Columbus, OH 43205 
Phone: (614) 722-2865 
FAX: (614) 722-2897 
Email: GOGBank@nationwidechildrens.org  
 
Whole blood specimens can be shipped to the GOG Tissue Bank Monday through 
Friday for Tuesday through Saturday delivery. Please do not ship whole blood the day 
before a holiday. Use your own shipping container to ship specimens via FedEx priority 
overnight. 
 
When shipping whole blood specimens, please be aware that your Institution must 
comply with IATA standards (www.iata.org). If you have questions regarding your 
shipment, contact the GOG Tissue Bank at GOGBank@nationwidechildrens.org or by 
phoning 866-GOG-BANC (866-464-2262).  
 
To ship whole blood specimens you will need (1) a sturdy shipping container (e.g., a 
cardboard or styrofoam box), (2) a leak proof biohazard envelope with absorbent 
material*, (3) a puncture and pressure resistant envelope (e.g. Tyvek envelope), (4) an 
Exempt Human Specimen Sticker, and (5) a pre-paid FedEx air bill. 
 
*If you will be shipping whole blood specimens from more than one patient, please put 
each specimen in a separate plastic zip-lock bag before placing the specimens in the 
shipping bag. You may include up to four different blood specimens in one biohazard 
envelope. 
 
If you do not have these materials available at your Institution, you may order them 
from any supplier (e.g., Saf-T-Pak; Phone: 800-814-7484; Website: www.saftpak.com). 
 
Instructions for Shipping Whole Blood Using Your Own Shipping Container 
 
1. 
Place the whole blood specimen in a biohazard envelope containing absorbent 
material. Expel as much air as possible before sealing the bag. 
  


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NCI Version Date:  05/02/2016                                                                                                                              
 
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2. 
Wrap the biohazard envelope in bubble wrap or another padded material. 
 
3. 
Place the padded tube(s) into a Tyvek envelope. Expel as much air as possible 
before sealing the envelope. 
 
4. 
Place the Tyvek envelope in a sturdy shipping contained (e.g., cardboard FedEx 
box). 
 
5. 
Insert a copy of the SP Form(s) into the box.  
 
6. 
Attach an Exempt Human Specimen Sticker to the outside of the shipping 
container. 
 
7. 
Print a pre-paid FedEx air bill using the Kit Management application (found under 
Data Entry on the Web Menu page). Attach the air bill. 
 
8. 
Make arrangements for FedEx pick-up through your usual institutional 
procedure or by calling 800-238-5355. 
 
C. 
Frozen Serum and Tumor 
 
Frozen specimens can be shipped to the GOG Tissue Bank using the kit provided. Ship 
frozen specimens Monday through Thursday for Tuesday through Friday delivery. 
Please do not ship frozen specimens on Fridays or the day before a holiday. 
 
Instructions for Shipping Frozen Specimens Using a Specimen Kit  
 
1. 
Pre-fill the specimen kit about 1/3 full with dry ice. 
 
2. 
Place each frozen specimen in a separate zip-lock bag. 
 
3. 
Put the zip-lock bags in the biohazard envelope containing absorbent material. Put 
the secondary envelope into a Tyvek envelope. Expel as much air as possible 
before sealing all envelopes. 
 
4. 
Place the Tyvek envelope containing the frozen specimens into the kit and fill the 
chamber to the top with dry ice. 
 
5. 
Insert the SP Forms.  
 
6. 
Place the styrofoam cover on top of the kit. Tape the outer box of the kit closed 
with filament or other durable sealing tape. Please do not tape the inner 
(styrofoam) chamber.  
 
7. 
Print a pre-paid FedEx air bill using the Kit Management application (found under 
Data Entry on the Web Menu page). Attach the air bill. 
 
8. 
Attach the dry ice label (UN1845) and the Exempt Human Specimen sticker. 


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9. 
Arrange for FedEx pick-up through your usual Institutional procedure or by 
calling 800-238-5355.  
 
XI. 
Distributing Specimens for Laboratory Testing 
 
The GOG SDC and Tissue Bank (or alternate laboratory) will coordinate the distribution of 
specimens to approved investigators for laboratory testing. Specimen selection will be based 
on information regarding specimen procurement and condition as well as patient eligibility, 
evaluation criteria, statistical considerations, and relevant clinical information. 
 
For each shipment, bank staff will provide the investigator and the SDC an electronic file that 
includes an inventory of all specimens included in the shipment. 
 
The SDC will provide the investigator an electronic file containing the specimen identifiers 
with relevant information regarding specimen condition, suitability for testing, 
eligibility/evaluability for a given component of the research study, and fields for the 
laboratory data. Investigators will not be given access to any personal identifiers. 
 
Investigators will be responsible for the direct supervision and oversight of the laboratory 
testing performed and for keeping accurate records of all specimen testing. 
 
Investigators will ensure that the laboratory testing results are linked to the appropriate 
specimen-specific identifiers and are responsible for transferring relevant laboratory data to 
the SDC. 
 
A. 
FFPE 
 
Unstained sections of FFPE will be batch shipped to: 
 
Dr. Michael Birrer 
Massachusetts General Hospital 
Yawkey 9072 
55 Fruit St. 
Boston, MA 02114 
Phone: 617-726-8624 
Fax: 617-724-6898 
Email: mbirrer@partners.org  
 
B. 
Whole Blood 
 
DNA extracted from whole blood will be batch shipped to: 
 
Dr. Michael Birrer 
Massachusetts General Hospital 
Yawkey 9072 
55 Fruit St. 
Boston, MA 02114 


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NCI Version Date:  05/02/2016                                                                                                                              
 
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Phone: 617-726-8624 
Fax: 617-724-6898 
Email: mbirrer@partners.org 
 
C. 
Frozen Tumor 
 
Frozen tumor will be batch shipped to: 
 
Dr. Michael Birrer 
Massachusetts General Hospital 
Yawkey 9072 
55 Fruit St. 
Boston, MA 02114 
Phone: 617-726-8624 
Fax: 617-724-6898 
Email: mbirrer@partners.org  
 
XII. 
Banking Specimens for Future Research 
 
Specimens will remain banked in the GOG Tissue Bank and made available for approved 
cancer and/or non-cancer research projects if the patient in question has provided permission 
for the use of her specimens for future cancer and/or non-cancer research. The patient’s choices 
will be recorded on the informed consent document the patient signs and electronically via the 
online Specimen Consent Application. 
 
GOG Institutions can amend a patient’s choices regarding the future use of her specimens at 
any time if the patient changes her mind. 
 
If the patient does not give permission for the use of her specimens, the GOG Tissue Bank will 
be instructed to destroy (incinerate) any remaining specimens to insure that the patient’s wishes 
are honored.