Clinical trial NCT02059265
Conditions: Endometrial Clear Cell Adenocarcinoma Ovarian Clear Cell Cystadenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Uterine Corpus Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2014-02-14; Completion date: 2023-06-26
Enrollment: 35 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well dasatinib works in treating patients with ovarian, fallopian tube, endometrial, or peritoneal cancer that has come back or is persistent. Dasatinib may shrink patients' tumors by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

I. To assess the clinical activity of dasatinib in patients with recurrent or persistent ovarian, fallopian tube, primary peritoneal, and endometrial clear cell carcinoma using objective tumor response (complete and partial): in patients without loss of BRG-associated factor 250a (BAF250a) expression and in patients with loss of BAF250a expression.

SECONDARY OBJECTIVES:

I. To examine the nature and degree of toxicity in this patient population treated with this regimen in patients with and without loss of BAF250a expression.

II. To examine the progression-free survival and overall survival for this patient population receiving dasatinib in patients with and without loss of BAF250a expression.

TERTIARY OBJECTIVES:

I. To examine the agreement between BAF250a immunohistochemistry and AT rich interactive domain 1A (SWI-like) (ARID1A) mutation status using next generation sequencing performed in formalin-fixed, paraffin-embedded tumor tissue.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) 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 dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Dasatinib intervention 2: Laboratory Biomarker Analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Correlative studies

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 
 
i 
 
SUMMARY OF CHANGES 
For Protocol Amendment #5 
 
NCI Protocol #: GOG-0283 
Local Protocol #: GOG-0283 
 
NCI Version Date: May 18, 2016 
Protocol Date: May 18, 2016 
 
# 
Section 
Page(s) 
Comments 
1. 
Title 
Page 
1-3 
The NCI Version Date has been updated. 
Includes Amendments 1-5 has been added. 
Revised has been added to the footer 
2. 
3.11 
18 
Pathology eligibility has been updated.  
3. 
App VI 
75 
Contact information for distributing specimens for translational 
research has been updated 
 
4. 
ICD 
 
NCI Version Date has been updated. 
 


 
1 
 
PROTOCOL GOG-0283 
A PHASE II TRIAL OF DCTD-SPONSORED DASATINIB (NSC #732517 IND #120636) IN 
RECURRENT /PERSISTENT OVARY, FALLOPIAN TUBE, PRIMARY PERITONEAL, AND 
ENDOMETRIAL  CLEAR CELL CARCINOMA CHARACTERIZED FOR THE RETENTION OR 
LOSS OF BAF250a EXPRESSION 
NCI Version:  May 18, 2016 
Includes Amendments 1-5 
POINTS: 
PER CAPITA -10 
MEMBERSHIP -3 
Suggested TR Per Capita – Award based on specimen submission with 1 point for each FFPE and whole blood (MAX = 5 
points). 
Lead Organization: NRG/NRG Oncology 
STUDY CHAIR 
DAVID HYMAN, M.D. 
MEMORIAL SLOAN-KETTERING 
CANCER CENTER 
300 E 66th Street, Rm 1353 
New York, NY 10065 
PHONE: (646) 889-4544 
FAX: (646) 888-4586 
EMAIL: hymand@mskcc.org  
 
STUDY CO-CHAIR 
CAROL AGHAJANIAN, M.D. 
MEMORIAL SLOAN-KETTERING 
CANCER CENTER 
1275 York Avenue 
New York NY 10021 
PHONE: (212) 639-2252 
FAX: (212) 639-8865 
EMAIL: aghajanc@mskcc.org  
 
NURSE CONTACT 
KATHLEEN O’CONNOR, B.S.N. 
MEMORIAL SLOAN-KETTERING 
CANCER CENTER 
300 E 66th Street, Room 1353 
New York, NY 10065 
PHONE: (646) 888-4544 
FAX: (212) 639-2283 
EMAIL: oconnork@mskcc.org 
 
STUDY PATHOLOGIST 
ROBERT SOSLOW, M.D. 
(SEE GOG WEBSITE DIRECTORY) 
 
TRANSLATIONAL RESEARCH CO-CHAIR 
DOUGLAS A. LEVINE, M.D. 
(SEE GOG WEBSITE DIRECTORY) 
 
TRANSLATION RES. SCIENTIST 
HEATHER A. LANKES, PhD, MPH 
(SEE GOG WEBSITE DIRECTORY) 
STUDY STATISTICIAN 
WILLIAM BRADY, PhD 
(SEE GOG WEBSITE DIRECTORY) 
 
 
 
OPEN TO PATIENT ENTRY FEBRUARY 3, 2014;  
TEMPORARILY CLOSED TO PATIENT ENTRY DECEMBER 19, 2014; REVISED 
NOVEMBER 2, 2015; REOPENED TO PATIENT ENTRY NOVEMBER 9, 2015; REVISED 
JANUARY 27, 2016; REVISED 


2 
 
Clinical Screen
Patient
Eligible
BAF250a
LOSS
BAF250a 
RETAINED
Patients with recurrent or persistent ovarian, fallopian tube, peritoneum, endometrial, or endometriosis-associated 
clear cell carcinoma.
Must be ≥ 50% clear cell histomorphology and be negative for expression of the WT-1 antigen and estrogen 
reception (ER) antigen by immunohistochemistry (IHC)
SCHEMA
(1) Enter patient into Screening application
on GOG Web Menu
(2) Submit five unstained FFPE tumor tissue slides to central
study laboratory for determination of
BAF250a immunohistochemistry (IHC) status
Treatment Initiated, Dasatinib 140mg daily, Days 1-28
1 cycle = 28 days
CT scan every 2 cycles (8 weeks)
Treatment continues until POD or adverse effects prohibit further therapy.
Depending on the results of Stage 1, there are two possible enrollment scenarios for 
Stage 2 (if Stage 2 is opened):
   1) Enrollment of both patients with and without loss of BAF250a expression.
   2) Enrollment of patients only with loss of BAF250a expression.
Register patient
(Note: once, the required number of patients are reached in one of the groups, 
that group will no longer be enrolled.)
Loss
Group open to 
enrollment?
Retained
Group open to 
enrollment?
Patient not 
eligible
No
No
Yes
Yes
(11/2/15) 


3 
 
 
TABLE OF CONTENTS 
PAGE 
1.0 
OBJECTIVES 
5 
1.1 
Primary Objectives: 
5 
1.2 
Secondary Objectives 
5 
1.3 
Translational Research Objectives 
5 
2.0 
BACKGROUND AND RATIONALE 
6 
2.1 
Rationale for a Clear Cell Carcinoma Specific Trial 
6 
2.2 
Rationale for Inclusion of Ovarian and Endometrial Clear Cell Carcinoma 
6 
2.3  
Rationale for Dasatinib in Gynecologic Clear Cell Carcinoma 
6 
2.4 
Rationale for Using BAF250a Expression as a Marker for ARID1A Mutation  
Status  
10 
2.5 
Dasatinib 
11 
2.6 
Rationale for Examining Dasatinib in Patients based on BAF250 Expression 17 
2.7 
Inclusion of Women and Minorities 
17 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS 
18 
3.1 
Eligible Patients 
18 
3.2 
Ineligible Patients 
20 
4.0 
STUDY MODALITIES 
22 
4.1  
Dasatinib (BMS-354825) NSC# 732517 
22 
5.0 
TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE 
29 
5.1 
Patient Screening and Registration (11/2/15) 
29 
5.2 
Treatment Plan 
31 
5.3 
Criteria for removal from treatment 
32 
6.0 
TREATMENT MODIFICATIONS 
33 
6.1 
Dose Modifications 
33 
6.2 
Selected Agent-Related Hematologic and Non-Hematologic Adverse Events 33 
6.3 
General Management Guidelines for Agent-Related Non-Hematologic Toxicity34 
7.0 
STUDY PARAMETERS 
36 
7.1 
Observations and Tests (11/2/15) 
36 


4 
 
7.2 
CENTRAL PATHOLOGY REVIEW 
37 
7.3  
Translational Research 
38 
8.0 
EVALUATION CRITERIA 
40 
8.1 
Antitumor Effect – Solid Tumors 
40 
9.0 
DURATION OF STUDY 
48 
9.1  
Patients will continue on study until disease progression or adverse effects 
48 
9.2 
All patients will be treated (with completion of all required case report 
48 
9.3 
A patient is considered off study therapy when the patient has progressed 
48 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES 
49 
10.1 
ADVERSE EVENT REPORTING FOR AN INVESTIGATIONAL AGENT 49 
10.2 
 GOG DATA MANAGEMENT FORMS 
52 
11.0 
STATISTICAL CONSIDERATIONS 
55 
11.1 
Design Summary: 
55 
11.2 
Principal Parameters: 
55 
11.3 
Accrual: 
55 
11.4 
Primary Hypothesis, Sample Size, and Design 
56 
11.5 
Evaluability for efficacy and toxicity 
57 
11.6 
Data Safety and Monitoring 
57 
11.7 
Secondary Endpoints and Exploratory Analyses 
58 
11.8 
Anticipated Gender and Minority Inclusion: 
58 
12.0 
BIBLIOGRAPHY 
59 
Appendix I - NCI/DCTD Standard Protocol Language 
62 
APPENDIX II - NRG Oncology General Therapy Guidelines (11/2/15) 
64 
Appendix III - Patient Medication Calendar 
65 
Appendix IV - BAF250a IMMUNOHISTOCHEMISTRY TESTING 
67 
Appendix V - BAF250a IMMUNOHISTOCHEMISTRY REQUISITION 
69 
Appendix VI - Translational Research Specimen Procedures 
70 
 


GOG-0283 
 
5 
 
1.0 
OBJECTIVES 
 
1.1 
Primary Objectives:  
To assess the clinical activity of dasatinib in patients with recurrent or persistent 
ovarian, fallopian tube, primary peritoneal, and endometrial clear cell carcinoma 
using objective tumor response (complete and partial): 
• in patients without  loss of BAF250a expression, and  
• in patients with loss of BAF250a expression 
 
1.2 
Secondary Objectives 
 
1.21 
To examine the nature and degree of toxicity in this patient population  
treated with this regimen in patients with and without  loss of BAF250a 
expression. 
 
1.22 
To examine the progression-free survival and overall survival for  
this patient population receiving dasatinib in patients with and without loss 
of BAF250a expression. 
 
1.3 
Translational Research Objectives 
 
1.31 
To examine the agreement between BAF250a  
immunohistochemistry and ARID1A mutation status using next 
generation sequencing performed in formalin-fixed, paraffin-embedded 
tumor tissue. 
 


GOG-0283 
 
6 
 
 
2.0 
BACKGROUND AND RATIONALE 
 
2.1 
Rationale for a Clear Cell Carcinoma Specific Trial 
 
Approximately 22,000 cases of ovarian cancer and 46,000 cases of endometrial 
are diagnosed in the United States annually.1 The majority (≥80%) of these cases 
are of the serous (ovarian) or endometrioid (endometrial) histologies. Although 
the precise frequency of clear cell carcinoma of the ovary and endometrium varies 
by continent, this orphan disease represents only 3-5% of cases in the first-line 
clinical trials for ovarian cancer.2 Several meta-analyses have evaluated the 
outcome of large numbers of patients treated in first-line ovarian cancer clinical 
trials and have found that clear cell histology is an independent poor-prognostic 
feature.2, 3 Matched by stage, clear cell cancers have a lower-response rate to 
standard platinum-based chemotherapy, a higher recurrence rate, and inferior 
survival when compared to serous ovarian cancers.4 Consensus panels of 
gynecologic cancer experts have called on researchers to acknowledge these 
differences and design clear cell specific clinical trials moving forward.5 
 
2.2 
Rationale for Inclusion of Ovarian and Endometrial Clear Cell Carcinoma 
 
Historically, distinctions have been made between clear cell carcinomas of the 
gynecologic tract arising from the ovary and endometrium. Recently, however, 
molecular profiling has demonstrated that both clear cell carcinomas are patho-
physiologically linked to—and represent malignant transformation of—
endometriosis.6, 7 Clear cell ovarian carcinomas of the ovary, arising from 
endometriosis, and clear cell endometrial carcinomas arising de novo in the 
endometrium and are therefore increasingly viewed as a single disease entity with 
a shared genetic lineage.   
 
2.3  
Rationale for Dasatinib in Gynecologic Clear Cell Carcinoma 
 
As described above, we now understand that endometrial and gynecologic clear 
cell carcinomas are associated with endometriosis.7  In 2010, a report in the 
NEJM identified that ARID1A mutations are present in approximately 50% of 
endometriosis-associated clear cell carcinomas.8 ARID1A is a putative tumor 
suppressor gene that encodes a protein BAF250a.9 BAF250a is involved in 
chromatin remodeling and it is believed that dysregulation of this protein may 
alter the accessibility of transcription factors to chromatin. The central importance 
of ARID1A mutations to the genetic events associated with transformation of 
endometriosis into clear cell carcinoma is supported by the recent reports that 
ARID1A mutations are almost universally present in the precursor lesions 
adjacent to ARID1A-deficient gynecologic clear cell carcinomas including non-
atypical endometriosis, atypical endometriosis, and borderline clear-cell 
adenofibromas.10 Furthermore, the loss of ARID1A expression has been linked to 
shorter progression free survival and chemoresistance of endometriosis associated 


GOG-0283 
 
7 
 
clear cell carcinomas.11 A functional profiling of endometriosis associated clear 
cell carcinomas was recently presented at the 2012 ASCO meeting.12 An siRNA 
kinome screen identified colony stimulating factor-1 receptor (CSF1R) as a 
synthetically lethal target of ARID1A-deficient but not ARID1A-intact 
endometriosis associated clear cell carcinoma cell lines (Figure 1). The synthetic 
lethality of CSF1R inhibitor in ARID1A-deficient clear cell carcinomas was 
maintained across multiple cell lines. CSF1R is a member of the type II receptor 
tyrosine kinase family characterized by five immunoglobulin-like extracellular 
domains and a kinase insert.  CSF1R has been correlated with tumor invasiveness 
and poor prognosis in breast cancer.13 Dasatinib, a small molecule inhibitor of 
BRC-ABL, is also known to inhibit CSF1 at single-digit nanomolar 
concentrations.14 The ability of dasatinib to selectively inhibit ARID1A-deficient 
endometriosis associated clear cell lines at physiologically achievable levels (1-
10nM) in a series of confirmatory experiments (Figure 2).12 Finally, to 
demonstrate that CSF1R was the therapeutic target of dasatinib, ARID1A mutant 
and wild-type cell lines were treated with the selective CSF1R inhibitor, 
GW2580, again demonstrating selective inhibition (Figure 3). 
 


GOG-0283 
 
8 
 


GOG-0283 
 
9 
 


GOG-0283 
 
10 
 
 
2.4 
Rationale for Using BAF250a Expression as a Marker for ARID1A Mutation 
 
Status 
 
ARID1A is a large gene with over 80,000 base pairs and 20 exons. As is typical 
for large tumor suppressor genes, nonsense, missence, insertion and deletion 
mutations of ARID1A have been described across the entire length of the gene, 
the majority of which are protein truncating. The lack of a small number of “hot-
spot” mutations, as well as the overall size of the gene, make tumor selection by 
prospective sequencing challenging. Moreover, mutation data alone does not 
necessary provide information on the functional impact on BAF250a expression. 
Fortunately, loss of BAF250a expression as detected by immunohistochemistry 
(IHC) correlates well with presence ARID1A mutation with an estimated 
sensitivity and specificity of 73% and 89%, respectively.8, 10 Figure 4 
demonstrates representative BAF250a IHC in ovarian clear cell carcinoma 
samples. It is therefore reasonable to use BAF250a expression as a surrogate for 
ARID1A-difficient clear cell carcinomas. Because ARID1A mutations are an 
early event in the development of endometriosis associated clear cell carcinomas, 
BAF250a IHC status in archival tissue from the time of diagnosis should be 
reflective of the status in recurrent or persistent metastatic lesions. 


GOG-0283 
 
11 
 
 
 
 
 
 
2.5 
Dasatinib 
 
Dasatinib (BMS-354825), an aminothiazole analogue, is an orally administered 
(PO) protein tyrosine kinase (PTK) inhibitor with specificity for five 
kinases/kinase families that have been strongly linked to multiple forms of human 
malignancies17- 19.  These targets include:  BCR-ABL, c-SRc, c-KIT, PDGFβ 
receptor, and EPHA2.  In vivo and in vitro studies have established that dasatinib 
demonstrates potent antiproliferative activity in a wide spectrum of cancer cell 
lines/types, and clinical results suggest anticancer activity of dasatinib in chronic 
myelogenous leukemia (CML) and solid tumor patients20-23.  
 
Dasatinib potently and selectively inhibits the five oncogenic PTKs/kinase 
families by competing with ATP for the ATP-binding sites in the kinases:  SRC 
family kinases (IC50:  SRC = 0.55 nM, LCK = 1.1 nM, YES = 0.41 nM, FYN = 
0.2 nM); BCR-ABL (<3 nM); c-KIT (13 nM); EPHA2 (17 nM) and PDGF 
receptor (28 nM) 17.  The agent was found to be less potent against unrelated 
PTKs and several serine/threonine kinases.  Dasatinib also demonstrates potent 
inhibition of VEGF- and bFGF-driven proliferation of human umbilical vein 
endothelial cells (HUVECs), with IC50 values of 43 and 248 nM, respectively. 
 


GOG-0283 
 
12 
 
BCR-ABL, a constitutively active cytoplasmic tyrosine kinase, is present in >90% 
of all patients with CML and in 15-30% of adult patients with acute 
lymphoblastic leukemia (ALL).  The inhibition of BCR-ABL by imatinib, another 
PTK inhibitor, is effective in the management of CML thus providing proof-of-
concept for targeting PTKs.  However, resistance to imatinib therapy associated 
with BCR-ABL gene mutation/over-expression and activation of selected SRC 
kinases has been increasingly encountered24.  Dasatinib has activity in a number 
of imatinib-resistant tumors25- 27, 29, 30 in addition to being 500-fold more potent 
than imatinib in inhibiting BCR-ABL.  The ability of dasatinib to inhibit imatinib-
resistant forms of BCR-ABL is presumed to be due to its relaxed binding 
requirements because, unlike imatinib which binds only to the inactive 
conformation of the BCR-ABL kinase, dasatinib binds to both the active and 
inactive conformations31.    
 
2.51  
Nonclinical Studies 
 
Efficacy 
Dasatinib inhibits growth of multiple BCR-ABL-dependent leukemic cell 
lines and also shows activity against 14 of 15 imatinib-resistant BCR-ABL 
kinase mutants29.  Inhibition of CML cell lines established from patients 
who were resistant to imatinib therapy has also been reported23.  Dasatinib 
potently inhibits wild-type (IC50:  1-10 nM) and mutant (IC50:  10-100 nM) 
KIT kinases in M07E cells and human mast cell leukemia cell lines, 
respectively22.  Also of note, dasatinib selectively killed primary 
neoplastic bone marrow mast cells from patients with systemic 
mastocytosis while sparing other hematopoietic cells28. 
 
Dasatinib demonstrated antiproliferative activity in a wide-spectrum of 
solid tumor types, including mastocytoma, prostate, and breast cell lines 
with IC50 values ranging from 5.4-103 Nm18.  The agent also inhibited 
stem cell factor-driven proliferation of three small cell lung cancer 
(SCLC) cell lines with IC50 values in the range of 114-220 nM and 
showed activity in head and neck squamous cell carcinoma and non-small 
cell lung cancer cell lines32. 
 
When dasatinib was administered twice daily (BID) on a 5-days-on/2-
days-off schedule for a total of 14 to 25 days at doses of 10-50 
mg/kg/dose, in vivo antitumor activity of dasatinib was seen in prostate, 
colon, breast, and pancreatic  xenograft models18.  Similarly, dasatinib was 
effective against K562 and imatinib-resistant K562-R human CML 
xenografts in SCID mice at doses as low as 2.5-5 mg/kg/day26.  In 
combination with docetaxel, dasatinib produced antitumor 
effects against PC3 human prostate carcinoma xenografts that 
were substantially better than the effects of either single 
agent alone18. 
 


GOG-0283 
 
13 
 
Dasatinib at 20 or 50 mg/kg inhibited the T-cell 
proliferation response in mice following the transfer of 
lymphocytes from allogeneic donor mice17.  In addition, 
treatment of mice with dasatinib 25 mg/kg BID inhibited the 
graft-versus-host response in a non-vascularized model of 
murine heart transplant.  The 5-days-on/2-days-off regimen 
almost completely eliminated immunosuppressive activity in 
this model. 
 
SRC kinase is known to play a major role in osteoclast function.  In short-
term studies, dasatinib acted as a potent inhibitor of bone resorption as 
measured by its ability to reduce the release of 45calcium into the culture 
medium by fetal rat long bones in vitro (IC50 = 2 nM).  Dasatinib also 
inhibited parathyroid hormone (PTH)-stimulated release of 45calcium in a 
dose-dependent manner with an apparent IC50 of 2 nM.  At 5 nM, 
dasatinib completely blocked PTH-stimulated bone resorption in thyro-
parathyroidectomized rats.  The therapeutic utility of dasatinib in the 
treatment of cancer-related hypercalcemic syndromes has not been fully 
explored, and the long-term effects of dasatinib on bone physiology are 
also unknown. 
 
Nonclinical Pharmacokinetic and Pharmacodynamic Studies  
Nonclinical metabolic and pharmacokinetic (PK) studies were conducted 
with dasatinib in several species including mouse, rat, dog, and monkeys 
to assess the absorption, distribution, metabolism, and excretion of the 
compound in animals.  These studies showed that dasatinib has varying 
degrees of oral bioavailability, ranging from 15% in monkeys to 34% in 
dogs.  The permeability of dasatinib in the Caco-2 cell model is 102 
nm/sec at pH 7.4, suggesting that it has the potential for good (>50%) oral 
absorption in humans.  The agent is highly bound to serum proteins 
(>91%) and has extensive extravascular distribution.  Dasatinib is 
principally eliminated by hepatic metabolism and excreted in feces.  The 
agent is primarily metabolized by the CYP3A4 enzyme to produce 
multiple metabolites.   
 
The value of phospho-SRC as a biomarker of dasatinib efficacy has been 
explored in nonclinical studies33.  In nude mice bearing subcutaneous PC-
3 tumors (human prostate), measurement of phospho-SRC by western blot 
in tumor and peripheral blood mononuclear cells (PBMCs) following 
treatment with a single dose of dasatinib (15 or 50 mg/kg) produced 
similar results in both tissues.  Levels of phospho-SRC were maximally 
inhibited at 3 hours post dose, then recovered partially between 7 and 17 
hours and returned to the basal level by 24 hours after agent 
administration.  These results were quantitated by image scanning and 
compared to efficacy results when the agent was administered PO BID at 


GOG-0283 
 
14 
 
15-50 mg/kg/dose for 14 days on a 5-days-on/2-days-off schedule.  
Efficacy and phospho-SRC inhibition appeared to correlate, and this 
pharmacodynamic model permitted the authors to predict that the plasma 
concentration of dasatinib required to produce 90% inhibition of phospho-
SRC would be 164 nM and 91 nM in PC-3 tumor and PBMCs, 
respectively.  Studies to evaluate the clinical utility of phospho-SRC as a 
biomarker are ongoing. 
 
Toxicology 
A range of toxicology studies have been conducted to support the oral 
administration of dasatinib in humans.  The oral studies indicated that 
dasatinib induced reversible toxicities of the gastrointestinal (GI) and 
lymphoid systems in rats and monkeys, and of the hematopoietic system in 
rats.  Embryo fetal development studies in rats and rabbits indicated that 
dasatinib caused embryo lethality or skeletal malformations at doses that 
did not cause maternal toxicity, suggesting that it is a selective 
developmental toxicant.  An in vitro cytogenetics study in CHO cells 
indicated that it was clastogenic at concentrations >5 μg/mL, a level not 
achievable in vivo.  The agent is nongenotoxic and did not show 
significant potential for undesirable functional activity in 
in vitro receptor/ion channel binding and enzyme assays.  In 
vitro potassium channel current (HERG/IKr) and Purkinje fiber assays 
suggested that dasatinib could potentially prolong cardiac ventricular 
repolarization (QT interval), and a single-dose cardiovascular study in 
monkeys demonstrated that the agent at a dose of 10 mg/kg caused a 
minimal increase in blood pressure for approximately 2 hours post dose.  
There were no drug-related neurologic observations in rats 
or monkeys.  Dasatinib was found to be phototoxic in an in 
vitro assay in mouse fibroblasts. 
 
2.52 
Clinical Experience 
 
Over 2000 subjects have received dasatinib, the majority with CML 
refractory or intolerant to imatinib18.  Studies conducted in healthy 
volunteers include the following:  PK; formulation comparisons; the effect 
of food; drug interactions; and supportive care.  Data are available from 11 
phase 1 and phase 2 studies in patients with CML, Philadelphia 
chromosome-positive (Ph+) ALL, or solid tumors using different dosage 
regimens and designed to determine PK, pharmacodynamic, safety, and 
efficacy in these populations.  
 
Pharmacokinetics 
Pharmacokinetic (PK) studies were conducted using a single 100 mg dose 
of dasatinib administered to healthy volunteers in four different 
formulations:  50 mg clinical tablets x 2, 5 mg clinical tablets x 20, 20 mg 
commercial tablets x 5, and 50 mg commercial tablets x 2.  The PK profile 


GOG-0283 
 
15 
 
of the agent was similar in all four formulations.  The PK profile of 
dasatinib was also assessed in CML and Ph+ ALL patients providing data 
which showed that the PK parameters in the patient population appear to 
be similar to that in the healthy volunteers.  The agent was absorbed 
rapidly following oral administration; peak plasma concentrations were 
achieved in 0.5-3 hours and dose-related increases in plasma 
concentrations were observed.  The mean terminal half-life (t1/2) of 
dasatinib was 4 hours.  Dosing interval exposures and t1/2 values were 
comparable regardless of whether the agent was administered on a once 
daily or twice daily (BID) 5-day-on/2-day-off schedule, or BID 
continuously.    
A phase 1 study has been initiated in solid tumor patients to determine the 
effect of the CYP3A4 inhibitor ketoconazole on dasatinib PK.  In a 
study of 18 patients with solid tumors, 20 mg of dasatinib 
once daily co-administered with 200 mg of ketoconazole twice 
daily increased the dasatinib Cmax and AUC by four- and 
five-fold, respectively. 
 
Efficacy 
A phase I study treated patients with CML in chronic phase (CP) or 
advanced disease (accelerated phase or blast crisis) or Ph+ ALL who were 
intolerant or resistant to imatinib34, 30.  Dasatinib was administered once 
daily at doses ranging from 15 to180 mg/day or BID at doses ranging from 
25 to 50 mg for 5-7 consecutive days each week.  Complete hematologic 
response was documented in 37 of 40 CP patients (92%) and the rate was 
similar with both schedules (once daily or BID).  Fourteen CP patients 
(35%) achieved a complete cytogenetic response and four (10%) 
experienced partial responses.  In 44 patients with advanced CML or Ph+ 
ALL, 31 major hematologic responses were documented (70%).  
Cytogenetic responses were documented in 25 advanced CML or ALL 
patients, including complete responses in 11 patients. 
 
A phase 1 study has been conducted in patients with refractory solid 
tumors in order to evaluate the safety, tolerability, and the pharmacologic 
profile of dasatinib20.  Patients received escalating doses (25 to 120 mg) of 
dasatinib without food administered BID for 5 consecutive days every 
week followed by 2 days of rest (5D2 schedule), or on a continuous daily 
dosing (CDD) schedule.  There were no objective responses on CT scans, 
but stable disease (SD) was observed in 11 patients (16%), including three 
gastrointestinal stromal tumor (GIST) patients.  These 11 were comprised 
of seven (21%) of 33 patients on the 5D2 schedule and four (12%) of 34 
patients on the CDD schedule.  The median duration of SD was 3.6 
months (range 1.7 – 23.6 months).  The investigators noted that the 
clinical benefits of the agent in a subset of imatinib-resistant GIST patients 
have been encouraging. 
 


GOG-0283 
 
16 
 
In solid tumors, the recommended phase 2 dose for dasatinib was found to 
be 120 mg BID on the 5D2 schedule, or 70 mg BID on the CDD 
regimen20.  In October 2010, dasatinib was approved by the FDA for 
treatment of chronic, accelerated, and blast phase CML and Ph+ ALL with 
resistance or intolerance to imatinib.  Results from two phase 3 dose-
optimization studies supported starting doses of 100 mg once/day for CP 
CML and 140 mg once/day for imatinib-resistant accelerated phase CML, 
myeloid or lymphoid blast phase CML, or Ph+ ALL.  A randomized phase 
3 trial comparing dasatinib to imatinib led to FDA approval of dasatinib 
(100 mg once/day) for first-line therapy of newly diagnosed CML.  
 
Safety 
Myelosuppression, probably attributable to suppression of the Ph+ clone, 
was the most frequent adverse event (AE) in the phase 1 study in CML or 
Ph+ ALL, while the most significant AE was grade 3/4 thrombocytopenia 
(28%) 18.  Severe myelosuppression was reversible and easily managed 
with a short dose interruption; about 60% of patients required interruption 
of treatment, and the myelosuppression generally resolved within 3 
months, often in association with a cytogenetic response30.  Twenty-five 
percent of leukemia patients required a dose reduction.  In the phase 1 
study in solid tumor patients, hematologic AEs were uncommon:  two 
patients on the 5D2 schedule with grade 1 or 2 anemia developed grade 3 
anemia while on study drug, whereas on the CDD schedule one patient 
developed grade 4 neutropenia and another grade 3 anemia20.   
 
Non-hematologic AEs from the two phase 1 trials include GI intolerance 
(primarily diarrhea, nausea, and vomiting), GI hemorrhage, fatigue, 
dyspnea, anorexia, dehydration, fluid retention, pleural and pericardial 
effusion, a moderate increase in QTc F (with no QTc F >500 msec), 
elevated creatinine, depression, and tumor lyses syndrome.  In addition to 
these AEs, dasatinib treatment has the potential to produce skin rashes, 
other respiratory events, and CNS hemorrhage.  While neither 
immunosuppression nor osteoclast function abnormalities (e.g., 
osteoporosis) were observed in these short-term studies, SRC kinase 
inhibitors have the potential to cause these types of events.  
 
As of September 2010 in the overall population of 2840 subjects, a total of 
740 (26%) deaths were reported in adult dasatinib-treated subjects with 
CML or Ph+ ALL.  Of these 740 deaths, 296 occurred within 30 days of 
the last dose of study therapy.  Of the 740 deaths, 380 (51%) were due to 
disease progression and 11 (1.5%) have been positively attributed to study 
drug toxicity.  
 
2.53 
Potential Drug Interactions 
 


GOG-0283 
 
17 
 
Dasatinib is primarily metabolized by CYP3A4 and therefore, potent 
inhibitors of this enzyme are contraindicated (Investigator’s Brochure, 
2010).  Dasatinib is also a significant inhibitor of this hepatic enzyme but 
a weak inhibitor of other cytochrome enzymes, and the agent does not 
induce CYP3A4.  Thus, dasatinib may decrease the clearance of drugs that 
are significantly metabolized by the CYP3A4 enzyme, and caution should 
be used with concurrent use of such drugs or substances.  In a study in 
cancer patients, concomitant use of a potent CYP3A4 inhibitor 
(ketoconazole) produced >5-fold increase in exposure to dasatinib, while 
healthy subjects treated concurrently with dasatinib and a potent CYP3A4 
inducer experienced a 5-fold decrease in dasatinib exposure.  When the 
CYP3A4 substrate simvastatin was studied in combination with dasatinib, 
increased simvastatin exposure resulted, indicating the necessity of caution 
when dasatinib is administered with CYP3A4 substrates with a narrow 
therapeutic margin (e.g., cyclosporine). 
 
 
2.6 
Rationale for Examining Dasatinib in Patients based on BAF250 Expression 
 
Based on the above results showing that dasatinib selectively inhibits ARID1A-
deficient endometriosis associated clear cell lines at physiologically achievable 
levels (1-10nM), we expect dasatinib to be active in the histologic patient 
population under study here—if they have ARID1A mutations.  Moreover, we use 
BAF250 expression as a marker for ARID1A status as noted above. 
 
However, we investigate the efficacy of dasatinib in both patients with and 
without loss of BAF250 expression in the event that the agent works in an 
unselected patient population. 
 
2.7 
Inclusion of Women and Minorities 
 
The Gynecologic Oncology Group 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 patients into this protocol and therefore address the study 
objectives in a patient population representative of the entire clear cell ovarian, 
fallopian tube, peritoneal and endometrial cancer population treated by 
participating institutions. 
 
 


GOG-0283 
 
18 
 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS  
 
3.1 
Eligible Patients  
 
3.11 
Patients must have recurrent or persistent ovarian, fallopian tube, 
peritoneum, and endometrial clear cell carcinoma. Primary tumors must be 
at least 50% clear cell histomorphology in order to be eligible or have a 
histologically documented recurrence with at least 50% clear cell 
histomorphology. In addition, the tumors should be negative for 
expression of WT-1 antigen (with the exception of endometrial cancers 
where WT-1 stains are not required) and Estrogen Receptor (ER) antigen 
by immunohistochemistry. Focal, weak, ER staining of tumor cells (<5%) 
is permitted. Appropriate tissue sections must be available for histologic 
evaluation for central pathology review by GOG. Immunohistochemical 
stained slides for ER and WT-1 antigen must be available for review by 
GOG. (XX/XX/XX) 
 
• If the primary tumor had at least 50% clear cell histomorphology, a 
biopsy of the recurrent or persistent tumor is not required. 
However, immunohistochemical studies of the primary tumor for 
ER and WT-1 antigens should be performed and the slides 
submitted to the GOG for review. The percentage of clear cell 
histomorphology must be documented in the pathology report or in 
an addendum to the original report. If slides of the primary tumor 
are not available for review due to disposal of slides by the 
histology laboratory (typically 10 years after diagnosis), biopsy of 
recurrent or persistent disease is required. 
 
• If the primary tumor had less than 50% clear cell histomorphology 
(or if slides of the primary tumor are not available for review), a 
biopsy of the recurrent or persistent tumor is required to confirm at 
least 50% clear cell histomorphology and  lack of immuno-
reactivity for ER and WT-1 antigens by immunohistochemistry. 
The percentage of involvement must be documented in the 
pathology report or in an addendum to the original report. 
 
3.12 
Patients must have results from the determination of BAF250a 
immunohistochemistry (IHC) status (see Section 5.1 and Appendix IV) 
and must have a BAF250a expression status that is currently open to 
enrollment.  (11/2/15) 
 
3.13 
All patients must have measurable disease.  Measurable disease is defined 
by RECIST (version 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 


GOG-0283 
 
19 
 
measured by chest x-ray.  Lymph nodes must be > 15 mm in short axis 
when measured by CT or MRI (See section 8).  
 
3.14 
Patients must have had one prior platinum-based chemotherapeutic  
 
 
regimen for management of primary disease. Patients are allowed to  
 
 
receive, but are not required to receive, two additional cytotoxic regimens  
 
 
for management of recurrent or persistent disease. 
 
3.15 
Patients must be ≥ 3 weeks from last chemotherapy or radiation (6 weeks 
for nitrosoureas or mitomycin). 
 
3.16 
Patients must have progressed on, be ineligible for, or have declined 
participation in GOG-0254 provided that protocol is actively accruing 
patients. 
 
 
 
 
3.17 
Patients must have adequate organ function defined as follows: 
 
Bone Marrow: 
• Leukocytes ≥3,000/mcL 
• Absolute Neutrophil Count ≥1,500/mcL 
• Platelets  ≥100,000/mcL 
 
Renal: 
• Creatinine ≤ 1.5 times the ULN 
OR 
• 
Creatinine Clearance ≥ 60 mL/min/1.73 m2  
 
Hepatic: 
• Bilirubin ≤1.5 ULN 
• AST (SGOT) and ALT (SGPT) ≤ 3x ULN  
 
3.18 
Patients who are on concomitant medications that are STRONG inducers 
or inhibitors of the CYP3A4 enzyme should stop 2 weeks prior to first 
dose of dasatinib, if all other eligibility has been confirmed.  An updated 
list of STRONG CYP3A4 inducers and inhibitors can be found at: 
http://www.medicine.iupui.edu/clinpharm/ddis/ 
 
3.19 
QTc interval on electrocardiogram must be ≤ 480 msec (Fridericia 
correction). 
 
3.110 Patients who have received one prior regimen must have a GOG 
Performance Status of 0, 1 or 2.  Patients who have received two or more 
prior regimens must have GOG performance status of 0 or 1. 
 
3.111 Patients who have met the pre-entry requirements specified in Section 7.0. 
 


GOG-0283 
 
20 
 
3.112 Patients must have signed an approved informed consent and authorization 
permitting release of personal health information. 
 
3.2 
Ineligible Patients  
 
 
3.21 
Prior treatment with dasatinib, imatinib or nilotinib. 
 
3.22  As dasatinib can cause fluid shifts, patients with symptomatic effusions 
 
(pleural, pericardial, or peritoneal) and/or those who have required a 
 
procedure for symptomatic effusions within 4 weeks of start of dasatinib 
 
are ineligible. 
 
3.23  Patients with a history of cardiac disease including: (1) uncontrolled 
 
angina, congestive heart failure, or myocardial infarction within six 
 
months prior to study entry, (2) congenital long QT syndrome, (3) clinical 
 
significant ventricular arrhythmias. 
 
3.24  The concomitant use of H2 blockers and proton pump inhibitors (PPIs)  
with dasatinib is not recommended. The use of antacids should be 
considered in place of H2 blockers or proton pump inhibitors in patients 
receiving dasatinib therapy. If antacid therapy is needed, the antacid dose 
should be administered two hours before or after the dose of dasatinib. 
Patients who cannot tolerate discontinuation of H2 blockers or PPIs are 
ineligible. 
 
3.25  Therapeutic anticoagulation is not contraindicated, but for those patients  
on therapeutic anticoagulation, alteration in coagulation parameters is 
expected following initiation of dasatinib. For patients on therapeutic 
anticoagulation, coagulation parameters should be assessed weekly for the 
first cycle following initiation of dasatinib, weekly for the first cycle 
following a dose reduction, and weekly for a minimum of two weeks after 
stopping dasatinib. 
 
3.26 
Patients whose circumstances do not permit completion of the study or the 
required follow-up. 
 
3.27  Patients who are pregnant or nursing. The effects of dasatinib on the 
developing human fetus are unknown.  For this reason and because protein 
thyrosine kinase inhibitors are known to be teratogenic, women of child-
bearing potential must agree to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) prior to study entry and for the 
duration of study participation and for 3 months after completion of 
therapy.  Should a woman become pregnant or suspect she is pregnant 
while she or her partner is participating in this study, she should inform 
her treating physician immediately.   A negative serum pregnancy test 
within 72 hours of starting drug is required. 


GOG-0283 
 
21 
 
 
3.28 
Patients under the age of 18. 
 
3.29  Patients who have a major surgical procedure, or significant traumatic 
injury within 28 days prior to the first date of treatment on this study, or 
anticipation of need for major surgical procedure during the course of the 
study; patients with placement of vascular access device or core biopsy 
within 7 days prior to the first date of treatment on this study.  
 
3.210  Patients with other invasive malignancies, with the exception of non 
melanoma skin cancer, who had (or have) any evidence of other cancer 
present within the last 5 years or whose previous cancer treatment 
contraindicates this protocol therapy. 
 
3.211 HIV-positive patients on combination antiretroviral therapy are ineligible 
because of the potential for pharmacokinetic interactions with dasatinib.  
In addition, these patients are at increased risk of lethal infections when 
treated with marrow-suppressive therapy. 
 
3.212 Patients who are unable to swallow pills. 
 
 
 


GOG-0283 
 
22 
 
4.0 
STUDY MODALITIES   
 
4.1  
Dasatinib (BMS-354825) NSC# 732517 
 
 
 
4.11 
Chemical Name:  N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)- 
 
 
 
1-piperazinyl]-2methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide,  
 
 
 
monohydrate 
 
4.12 
Mechanism of Action:  Dasatinib is a potent, broad spectrum ATP-
competitive inhibitor of 5 critical oncogenic tyrosine kinase families:  BCR-
ABL, SRC family kinases, c-KIT, ephrin (EP) receptor kinases, and PDGFβ 
receptor.  Overexpression or activation of these kinases plays critical roles 
in the etiology of various cancer types 
 
4.13 
Molecular formula:  C22H26CIN7O2S· H20 
MW: Dasatinib monohydrate: 
506.02 daltons 
 
 
4.14 
Approximate Solubility:  Dasatinib’s solubility ranged from 18.42 mg/mL 
at pH 2.6 to < 0.001 mg/mL at pH 7. 
 
4.15 
How Supplied:  BMS supplies and CTEP, NCI, DCTD distributes dasatinib. 
Dasatinib is available in the following tablet/bottle sizes: 
 
• 5 mg round, plain white film-coated tablets containing 30 tablets per bottle. 
• 20 mg biconvex round, white to off-white film-coated tablets containing 30 
tablets per bottle.  The tablet is debossed with “20” on one side and “527” on 
the other side. 
• 50 mg biconvex oval, white to off-white film-coated tablets containing 30 
tablets per bottle.  The tablet is debossed with “50” on one side and “528” on 
the other side.  
   
Inactive ingredients include lactose, microcrystalline cellulose, 
croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate. The 
film-coating contains hypromellulose, titanium dioxide, glycerol triacetate 
(in the 5 mg), and polyethylene glycol (in the 20 mg tablets and 50 mg 
tablets).  
 
 
Note:  The 5 mg tablets are restricted to pediatric trials. 
 
4.14 
Storage:  Store the intact bottles at controlled room temperature (15°C-
25°C) and protect from light.  
 
 
 
4.18 
Stability:  Stability studies are ongoing.  
 
 
 
 


GOG-0283 
 
23 
 
 
 
4.19 
Route of Administration:  Oral. Tablets may be taken with or without food.    
They should be swallowed whole and not crushed or broken. 
 
4.20 
Potential Drug Interactions:  Dasatinib is primarily metabolized by the 
human CYP3A4 enzyme; therefore, potent CYP3A4 inducers and inhibitors 
are prohibited on dasatinib trials. 
 
Concomitant use of dasatinib and a CYP3A4 substrate may increase 
exposure to the CYP3A4 substrate. Therefore, caution is warranted when 
dasatinib is co-administered with CYP3A4 substrates of narrow 
therapeutic index. 
 
Systemic antacids (both H2 receptor antagonists and proton pump inhibitors) 
are prohibited on dasatinib trials.  Locally acting antacids can be given up to 
two hours prior or two hours following dasatinib administration.   
 
Dasatinib may prolong the QT/QTc interval.  Use caution when 
administering dasatinib with other potential QTc-prolonging medications. 
 
Due to the possibility of CNS, gastrointestinal, cardiac, and cutaneous 
hemorrhage, use caution in patients who require medications that inhibit 
platelet function or anticoagulants.  
 
 
4.21 
Special Handling:  Dasatinib tablets consist of a core tablet (containing the  
active drug) surrounded by a film coating to prevent exposure to the active 
drug substance.  If tablets are accidentally crushed or broken, caregivers 
should wear disposable chemotherapy gloves. Pregnant women should avoid 
exposure to crushed and/or broken tablets.  
 
 
 
 
 
4.22 
Reported Adverse Events and Potential Risks: (01/27/16) 
 
 
 
 
Comprehensive Adverse Events and Potential Risks list (CAEPR) 
for 
Dasatinib (BMS-354825, Sprycel, NSC 732517) 
 
The Comprehensive Adverse Events 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 and italicized 
text. This subset of AEs (SPEER) is a list of events that are protocol specific exceptions to expedited 
reporting to NCI (except as noted below).  Refer to the 'CTEP, NCI Guidelines: Adverse Event Reporting 
Requirements' http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguidelines.pdf  
for further clarification.  Frequency is provided based on 2937 patients. Below is the CAEPR for Dasatinib 
(BMS-354825, Sprycel). 
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 


GOG-0283 
 
24 
 
agents and has an AE listed on different SPEERs, use the lower of the grades to determine if 
expedited reporting is required. 
 
 
Version 2.6, September 1, 20151 
 
 Adverse Events with Possible  
 Relationship to Dasatinib (BMS-354825, Sprycel) 
 (CTCAE 4.0 Term) 
[n= 2937] 
 
 
 
 Specific Protocol Exceptions 
to Expedited Reporting 
(SPEER)  
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
Anemia 
 
 
 Anemia (Gr 3) 
 
Febrile neutropenia 
 
  
CARDIAC DISORDERS 
  
 
 
Heart failure 
  
 
 
Left ventricular systolic 
dysfunction 
  
 
 
Myocardial infarction 
  
 
Pericardial effusion 
 
  
GASTROINTESTINAL DISORDERS 
  
 
Abdominal distension 
 
  
 
Abdominal pain 
 
 Abdominal pain (Gr 2) 
 
Anal mucositis 
 
  
 
Constipation 
 
  
Diarrhea 
 
 
 Diarrhea (Gr 3) 
 
Dyspepsia 
 
  
 
Gastrointestinal hemorrhage2 
 
  
 
Mucositis oral 
 
  
Nausea 
 
 
 Nausea (Gr 3) 
 
Rectal mucositis 
 
  
 
Small intestinal mucositis 
 
  
 
Vomiting 
 
 Vomiting (Gr 3) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
 
Edema limbs 
 
  
Fatigue 
 
 
 Fatigue (Gr 3) 
 
Fever 
 
 Fever (Gr 2) 
 
General disorders and 
administration site conditions - 
Other (generalized edema) 
 
  
 
General disorders and 
administration site conditions - 
Other (superficial edema) 
 
 General disorders and 
administration site conditions - 
Other (superficial edema) (Gr 2) 
 
Non-cardiac chest pain 
 
  
 
Pain 
 
  
INFECTIONS AND INFESTATIONS 
  
 
Infection3 
 
 Infection3 (Gr 3) 
INVESTIGATIONS 
  
 
Alanine aminotransferase 
increased 
 
  
 
Aspartate aminotransferase 
increased 
 
  
 
 
Electrocardiogram QT corrected 
interval prolonged 
  


GOG-0283 
 
25 
 
 
 Adverse Events with Possible  
 Relationship to Dasatinib (BMS-354825, Sprycel) 
 (CTCAE 4.0 Term) 
[n= 2937] 
 
 
 
 Specific Protocol Exceptions 
to Expedited Reporting 
(SPEER)  
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
 
 
Neutrophil count 
decreased 
 
 
 Neutrophil count decreased (Gr 3) 
Platelet count decreased 
 
 
 Platelet count decreased (Gr 4) 
 
Weight gain 
 
  
 
Weight loss 
 
  
 
White blood cell decreased 
 
 White blood cell decreased (Gr 3) 
METABOLISM AND NUTRITION DISORDERS 
  
 
Anorexia 
 
 Anorexia (Gr 3) 
 
Hypocalcemia 
 
  
 
Hypokalemia 
 
  
 
Hypophosphatemia 
 
 Hypophosphatemia (Gr 3) 
 
 
Tumor lysis syndrome 
  
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
  
 
Arthralgia 
 
  
Myalgia 
 
 
 Myalgia (Gr 2) 
NERVOUS SYSTEM DISORDERS 
  
 
Dizziness 
 
  
Headache 
 
 
 Headache (Gr 3) 
 
 
Intracranial hemorrhage 
  
 
 
Leukoencephalopathy 
  
 
 
Reversible posterior 
leukoencephalopathy syndrome 
  
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
 
Cough 
 
  
Dyspnea 
 
 
 Dyspnea (Gr 3) 
 
Laryngeal mucositis 
 
  
 
Pharyngeal mucositis 
 
  
Pleural effusion 
 
 
 Pleural effusion (Gr 3) 
 
Pneumonitis 
 
  
 
 
Pulmonary hypertension 
  
 
Tracheal mucositis 
 
  
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Alopecia 
 
  
 
 
Erythema multiforme 
  
 
Pruritus 
 
  
 
Rash acneiform 
 
  
Rash maculo-papular 
 
 
 Rash maculo-papular (Gr 2) 
 
 
Stevens-Johnson syndrome 
  
 
 
Toxic epidermal necrolysis 
  
VASCULAR DISORDERS 
  
 
Flushing 
 
  
 
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.  
 


GOG-0283 
 
26 
 
2Gastrointestinal hemorrhage includes Anal hemorrhage, Cecal hemorrhage, Colonic hemorrhage, 
Duodenal hemorrhage, Esophageal hemorrhage, Esophageal varices hemorrhage, Gastric hemorrhage, 
Hemorrhoidal hemorrhage, Ileal hemorrhage, Intra-abdominal hemorrhage, Jejunal hemorrhage, Lower 
gastrointestinal hemorrhage, Oral hemorrhage, Pancreatic hemorrhage, Rectal hemorrhage, 
Retroperitoneal hemorrhage, and Upper gastrointestinal hemorrhage under the GASTROINTESTINAL 
DISORDERS SOC. 
 
3Infection includes all 75 sites of infection under the INFECTIONS AND INFESTATIONS SOC. 
 
4Gastrointestinal ulcer includes Anal ulcer, Colonic ulcer, Duodenal ulcer, Esophageal ulcer, Gastric ulcer, 
Ileal ulcer, Jejunal ulcer, Rectal ulcer, and Small intestine ulcer under the GASTROINTESTINAL 
DISORDERS SOC. 
 
 
Adverse events reported on Dasatinib (BMS-354825, Sprycel) trials, but for which there is 
insufficient evidence to suggest that there was a reasonable possibility that Dasatinib (BMS-
354825, Sprycel) caused the adverse event: 
 
CARDIAC DISORDERS - Acute coronary syndrome; Atrial fibrillation; Cardiac disorders - Other 
(cardiomegaly); Cardiac disorders - Other (heart rate increased); Chest pain - cardiac; Myocarditis; 
Palpitations; Pericarditis; Sinus tachycardia; Ventricular tachycardia 
CONGENITAL, FAMILIAL AND GENETIC DISORDERS - Congenital, familial and genetic disorders - 
Other (Keratosis follicular) 
EAR AND LABYRINTH DISORDERS - Ear pain; Middle ear inflammation; Tinnitus; Vertigo 
EYE DISORDERS - Blurred vision; Conjunctivitis; Dry eye; Eye disorders - Other (optic nerve neuritis) 
GASTROINTESTINAL DISORDERS - Ascites; Colitis; Dry mouth; Dysphagia; Enterocolitis; Esophagitis; 
Flatulence; Gastritis; Gastrointestinal disorders - Other (anal fissure); Gastrointestinal disorders - Other 
(hematemesis); Gastrointestinal disorders - Other (mouth ulceration); Gastrointestinal disorders - Other 
(oral soft tissue disorder); Gastrointestinal disorders - Other (oropharyngeal pain); Gastrointestinal 
disorders - Other (tongue eruption); Gastrointestinal ulcer4; Ileus; Oral pain; Pancreatitis; Periodontal 
disease; Stomach pain 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Edema face; Edema 
trunk; Flu like symptoms; Gait disturbance; General disorders and administration site conditions - Other 
(temperature intolerance); Localized edema; Malaise 
HEPATOBILIARY DISORDERS - Cholecystitis; Hepatobiliary disorders - Other (cholestasis) 
IMMUNE SYSTEM DISORDERS - Anaphylaxis 
INFECTIONS AND INFESTATIONS - Infections and infestations - Other (herpes virus infection) 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Bruising 
INVESTIGATIONS - Alkaline phosphatase increased; Blood bilirubin increased; Cardiac troponin T 
increased; CD4 lymphocytes decreased; CPK increased; Creatinine increased; GGT increased; 
Investigations - Other (bone densitometry); Investigations - Other (EKG T-wave inversion); Investigations 
- Other (pancytopenia); Investigations - Other (thermometry abnormal); Lymphocyte count decreased; 
Lymphocyte count increased 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hyperkalemia; Hyperuricemia; 
Hypoalbuminemia; Hypomagnesemia; Hyponatremia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthritis; Back pain; Bone pain; 
Chest wall pain; Generalized muscle weakness; Musculoskeletal and connective tissue disorder - Other 
(epiphyses delayed fusion); Musculoskeletal and connective tissue disorder - Other (muscle spasm); 
Musculoskeletal and connective tissue disorder -  Other (muscle stiffness); Musculoskeletal and 
connective tissue disorder - Other (nuchal rigidity); Musculoskeletal and connective tissue disorder - 
Other (rhabdomyolysis); Musculoskeletal and connective tissue disorder - Other (tendonitis); Myositis; 
Osteoporosis; Pain in extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - Neoplasms 
benign, malignant and unspecified (incl cysts and polyps) - Other (hemangiomatosis) 
NERVOUS SYSTEM DISORDERS - Acoustic nerve disorder NOS; Amnesia; Cognitive disturbance; 
Concentration impairment; Dysarthria; Dysgeusia; Ischemia cerebrovascular; Lethargy; Peripheral motor 


GOG-0283 
 
27 
 
neuropathy; Peripheral sensory neuropathy; Seizure; Somnolence; Syncope; Transient ischemic attacks; 
Tremor 
PSYCHIATRIC DISORDERS - Anxiety; Confusion; Depression; Insomnia; Libido decreased; Suicidal 
ideation 
RENAL AND URINARY DISORDERS - Acute kidney injury; Proteinuria; Urinary frequency 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Gynecomastia; Irregular menstruation 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Adult respiratory distress syndrome; 
Bronchospasm; Epistaxis; Hypoxia; Pulmonary edema; Sore throat 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Bullous dermatitis; Dry skin; Hyperhidrosis; Nail 
loss; Pain of skin; Palmar-plantar erythrodysesthesia syndrome; Periorbital edema; Photosensitivity; 
Purpura; Skin and subcutaneous tissue disorders - Other (acute febrile neutrophilic dermatosis); Skin and 
subcutaneous tissue disorders - Other (hair color changes); Skin and subcutaneous tissue disorders - 
Other (panniculitis); Skin ulceration; Urticaria 
VASCULAR DISORDERS - Hematoma; Hot flashes; Hypertension; Hypotension; Phlebitis; Superficial 
thrombophlebitis; Thromboembolic event; Vasculitis 
 
 
Note: Dasatinib (BMS-354825, Sprycel) in combination with other agents could cause an exacerbation of 
any adverse event currently known to be caused by the other agent, or the combination may result in 
events never previously associated with either agent. 
 
 
 
4.23 
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 drug be shipped directly to the institution where the 
patient is being 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, Supplemental Investigator Data 
Form (IDF), and Financial Disclosure Form.  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. 
 


GOG-0283 
 
28 
 
 
 
 
 
 
 
 
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 the PMB using the NCI Drug Accountability Record 
Form (DARF). See the CTEP web site for Policy and Guidelines for 
Accountability and Storage of Investigational Drugs at 
http://ctep.cancer.gov/requisition/ 
 
 
 
 
 
 
 
Requests for Investigator’s Brochures (IB) should be e-mailed to 
ibcoordinator@mail.nih.gov or you may call the IB coordinator at 240-
276-6570. 
 
 
 
4.24 
Drug Returns:  Only unreconstituted drug supplies should be returned to  
 
 
 
 
 
 
the PMB. When it is necessary to return study drug, investigators should 
return the study drug to the PMB using the NCI Return Drug List 
available on the CTEP home page (http://ctep.cancer.gov) or by calling the 
PMB at 240-276-6575. 
. 


GOG-0283 
 
29 
 
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 Screening and Registration (11/2/15) 
 
When a suitable candidate has been obtained for protocol entry, the following 
steps should be taken: 
 
Screening 
 
When a suitable candidate has been identified for protocol entry, the following 
steps should be taken: 
 
• An approved informed consent form and authorization permitting the release 
of personal health information must be signed by the patient or guardian. 
Current FDA, NCI and institutional regulations concerning informed consent 
will be followed. 
 
• All eligibility requirements indicated in Section 3.0 must be satisfied, with the 
exception of 3.12 (BAF250a expression results). 
 
• Log onto the GOG website, go to the Web Menu page and open the link to 
Screening to obtain a Screening Patient Identifier. 
 
• Obtain five (minimum four) unstained sections (charged, 4-6µm). Label each 
individual slide with the Screening Patient Identifier. Slides may also be 
labeled with the pathology accession and block number, but these identifiers 
are not required. Do not label slides with any personal identifying information 
(e.g., patient name, patient initials, date of birth).  See Appendix IV for 
further details. 
 


GOG-0283 
 
30 
 
• Complete the GOG-0283 BAF250a Immunohistochemistry Requisition 
(Appendix V). Ensure the Screening Patient Identifier on the slides matches 
the Screening Patient Identifier on the requisition. 
 
• Ship the slides along with a de-identified copy of the corresponding pathology 
report (labelled with the Screening Patient Identifier) to: 
 
ATTN: Jessica Menzel 
Memorial Sloan-Kettering Cancer Center 
Department of Pathology 
1275 York Ave 
New York, NY 10065 
Phone: 212-639-7297 
Fax: 646-422-2070 
Email: menzelj@mskcc.org 
 
• Receive the results of the central pathology review on the Screening web 
application. 
 
• If the patient’s BAF250a expression status is one to which the trial is open, 
proceed to patient registration in GOG-0283. 
 
 
Registration 
 
5.11 
The eligibility check list data must be gathered. 
 
5.12 
All site staff will use OPEN to enroll patients to this study.  OPEN can be  
accessed at on the GOG web menu page and 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. 
• 
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.  


GOG-0283 
 
31 
 
• 
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.  
  
Note:  The OPEN system will provide the site with a printable 
confirmation of registration and treatment information.   Please print this 
confirmation for your records.  
  
 
5.13 
The institution must enter the patient’s name, and GOG patient study ID,  
in the appropriate place in their Log Book to verify the patient’s entry. 
 
NOTE: If this protocol switches to selective enrollment (see Section 11) of only 
patients with loss of BAF250a expression, the protocol accrual will briefly halt 
and the protocol will undergo an amendment to reflect new screening and 
registration procedures. (11/2/15) 
 
 
5.2 
Treatment Plan  
 
5.21 
Treatment will be administered on an outpatient basis. Patients will 
receive dasatinib 140mg by mouth, once daily, on days 1-28. One cycle is 
4 weeks long (28 days). Dasatinib tablets may be taken with or without 
food as desired, but should be swallowed with at least 8 ounces (240 mL) 
of water.  A light meal is not required, but may improve gastric tolerance 
for dasatinib.  Tablets must be swallowed whole and may not be broken.  
If vomiting occurs within 30 minutes of swallowing the tablet(s), the dose 
may be replaced if the tablets can be seen and counted.  Four weeks (28 
days) constitutes one cycle of treatment. 
 
Patients will be provided with a Medication Diary for dasatinib (Appendix 
III), instructed in its use, and asked to bring the diary along with all pill 
bottles with them to each appointment. 
 
Treatment interruptions of up to one cycle (4 weeks) are permitted for 
resolution of treatment-related toxicities. Failure of resolution of 
treatment-related toxicity within 4 weeks will require discontinuation of 
study treatment. 
Laboratory parameters for cycle 1 day 1 are detailed in the Eligibility 
Criteria, Section 3.17. 
Laboratory parameters for all subsequent visits are as follows: 
-Absolute neutrophil count ≥1,000/mcL 
-Platelets ≥75,000/mcL 
-Creatinine ≤ 1.5 times the ULN -OR- creatinine clearance (calculated or 
measured) ≥ 60 mL/min/1.73 m2  


GOG-0283 
 
32 
 
-Bilirubin ≤1.5 ULN 
-AST (SGOT)/ ALT (SGPT) ≤ 3x ULN 
Dose modification for toxicity will be made as specified in Section 6.0. 
See the NRG Oncology General Therapy Guidelines for appropriate 
treatment windows (Appendix II). 
 
Treatment may continue until patient demonstrates objective progression 
of disease or experiences unacceptable treatment-related toxicity 
(attributed as possibly related or greater). (11/2/15) 
 
5.3 
Criteria for removal from treatment 
 
5.31 
Inability to tolerate toxicity. 
5.32 
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. 
5.33 
Patients with substantial non-compliance with study protocols which, in 
the opinion of the investigator, compromises the patient’s participation in 
the protocol. 
5.34 
The reason for removal from treatment must be documented in the case 
report form. 


GOG-0283 
 
33 
 
6.0 
TREATMENT MODIFICATIONS    
 
6.1 
Dose Modifications 
 
Patients requiring dose modification of dasatinib will be managed as follows. 
Patients that require more than a two dose level reduction due to drug related 
adverse events will be removed from study. 
 
Dose Level 
Dasatinib Dose 
Starting Dose 
140 mg once daily 
(Two 50mg tablets, Two 20mg tablets) 
-1 
100 mg once daily 
(Two 50mg tablets) 
-2 
70 mg once daily 
(One 50mg tablet, One 20mg tablet) 
 
 
6.2 
Selected Agent-Related Hematologic and Non-Hematologic Adverse Events 
 
Event 
AE Grade or 
Observation 
Dose modification 
Neutropenia 
Grade 1 or 2 
Maintain dose 
Grade 3 or 4 1 
Hold dasatinib until < grade 2, then reduce 1 dose 
level and resume treatment  
Thrombocytopenia 
Grade 1 or 2 
Maintain dose 
Grade 3 or 4 1 
Hold dasatinib until < grade 2, then reduce 1 dose 
level and resume treatment 
Hemorrhage/Bleeding/ 
Coagulopathy 
(without thrombocytopenia) 
Grade 1 
No interruption in treatment; maintain current 
dose. 
Monitor as clinically indicated 
Grade 2 
Hold dasatinib until AE resolved to ≤ grade 1. 
Discontinue treatment and withdraw subject from 
study.3 Follow up per protocol (see Section 5.3) 
Grade 3 or 4 
Discontinue treatment and withdraw subject from 
study. 
Follow up per protocol (see Section 5.3). 
Hemorrhage/Bleeding/Coagulopathy 
(with thrombocytopenia2) 
Grade 1 
Hold dasatinib until thrombocytopenia resolved 
to ≤ Grade 1, then reduce 1 dose level and resume 
treatment. 
Monitor as clinically indicated. 
Grade 2 
Hold dasatinib until AE resolved to ≤ grade 1 and 
thrombocytopenia resolved to ≤ Grade 1. 
Discontinue treatment and withdraw subject from 
study.3 Follow up per protocol (see Section 5.3) 
Grade 3 or 4 
Discontinue treatment and withdraw subject from 
study. Follow up per protocol (see Section 5.3) 
QTc Prolongation 
Grade 1 or 2 
Maintain dose. 
Grade 3 (> 500 
ms) 
Hold dasatinib. Correct electrolyte abnormalities 
and discontinue any contributory concomitant 
medications. When AE resolved to ≤ Grade 2, 


GOG-0283 
 
34 
 
then resume treatment. 
 
First recurrence: Management as above, then 
reduce 1 dose level and resume treatment. 
 
Second recurrence: Stop dasatinib and remove 
patient from study. Follow up per protocol (see 
Section 5.3) 
Grade 4 (>500 ms 
AND Torsade de 
pointes OR 
Ventricular 
arrhythmia) 
Discontinue treatment and withdraw subject from 
study. Follow up per protocol (see Section 5.3). 
Pleural Effusion, Pericardial 
Effusion, or Ascites 
Grade 1 
Continue dasatinib. 
Grade 2 or 3 
Hold dasatinib until AE resolved to ≤ grade 1 and 
institute support measures (drainage and/or 
diuretics as clinically indicated). Reduce 
dasatinib by 1 dose level. Recurrent grade 3 
events require study removal. 
Grade 4 
Discontinue treatment and withdraw subject from 
study. 
Follow up per protocol (see Section 5.3). 
1 
These recurrent grade 3 events require a 2nd dose reduction; recurrent grade 4 events require study 
removal. 
2. Dose modification instructions for thrombocytopenia must also be followed. 
3. Under very limited circumstances, it may be appropriate to resume treatment following a Grade 2 
hemorrhage/bleeding/coagulopathy AE. These includes circumstances where the intervention required 
to address bleeding was minimal such as holding pressure on a superficial bleeding wound or nasal 
packing. Investigators much first seek permission from the Study Chair prior to resuming treatment 
following Grade 2 hemorrhage/bleeding/coagulopathy. Under these circumstances, dasatinib will be 
reduced by 1 dose level. If grade 2 hemorrhage/bleeding/coagulopathy resumes following dose 
reduction, stop dasatinib and remove patient from study. 
 
 
6.3 
General Management Guidelines for Agent-Related Non-Hematologic Toxicity 
 
Severity 
Management 
Grade 2 
1st event: 
Institute supportive therapy.  May hold dasatinib, or continue 
without dose reduction, or reduce by one dose level 
2nd event: Hold dasatinib and maximize supportive therapy.  Decrease dose 
by one dose level  
3rd event: 
Hold dasatinib.  May discontinue if AE poorly controlled. 
Grade 3 
1st event: 
Hold dasatinib.  Institute supportive therapy.  Restart dasatinib 
with reduction by one dose level allowed. 
2nd event: Hold dasatinib.  Maximize supportive therapy.  Dasatinib may be 
restarted or discontinued if dose already reduced. 
Grade 4 
1st event: 
Hold dasatinib.  Maximize supportive therapy.  Dasatinib may be 
restarted with dose reduction by one dose level or discontinued. 
 
 
In general, dose will not be re-escalated after a dose reduction. If, however, the 
investigator feels the patient would benefit from re-escalation and this could be 


GOG-0283 
 
35 
 
accomplished safely, it will be permissible with the explicit permission of the 
Study Chair or Co-Study Chair. 


GOG-0283 
 
36 
 
7.0 
STUDY PARAMETERS   
 
7.1 
Observations and Tests (11/2/15) 
The following observations and tests are to be performed and recorded on the 
appropriate form(s): 
 
PARAMETER 
Pre-
Therapy 
Prior to Each 
Treatment 
Cycle 
After Cycle 2, 
then every other 
cycle 
Follow up7 
Every 3 
months x 2 
years; then 
every 6 
months x 3 
years 
History & Physical  
1 
X 
 
X 
Performance Status 
1 
X 
 
X 
Height 
1 
 
 
 
Weight 
1 
6 
 
X 
Vital Signs (blood pressure, heart 
rate and temperature) 
1 
X 
 
X 
Toxicity Assessment 
1 
X 
 
X 
CBC, differential, hemoglobin, 
platelets, Electrolytes, BUN, 
Creatinine, Ca, Mg, PO4, Bilirubin, 
AST/SGOT, ALT/SGPT, Alkaline 
Phosphatase 
 
2 
6 
 
 
 
X 
PT, INR 
2, 5 
 
5 
 
 
 
Pregnancy test 
3 
 
 
 
CA125 
2 
X 
 
X 
Chest Imaging (CT of Chest) 
1 
 
9 
9† 
Radiographic disease assessment 
1 
 
4 
4† 
Electrocardiogram 
1 
8 
 
 
Patient diary documenting dasatinib 
dosing 
 
X 
 
 
Central Confirmation of BAF250a 
IHC Expression Loss (Section 5.1 
and Appendix V) 
X 
 
 
 
† Until disease progression or death or until patient is put on non-protocol cancer therapy 
 
1. Must be obtained within 28 days prior to initiating protocol therapy. 


GOG-0283 
 
37 
 
2. Must be obtained within 14 days prior to initiating protocol therapy. 
3. If in the investigator’s opinion the patient is of child-bearing potential. Must be obtained within 72 hours 
prior to initiating protocol therapy. 
4. CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months;  
then every 3 months x 2; then every 6 months thereafter until disease progression; and at any other time if 
clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum 
tumor marker levels. Note that radiology must be done to confirm response per Section 8.135 for CR and 
PR cases. 
5. PT/INR for patients on therapeutic anticoagulation. INR should be between 2 and 3 on a stable dose of 
warfarin (or other anticoagulant) or on stable dose of heparin prior to restarting treatment. Coagulation 
parameters should be assessed weekly for the first cycle following initiation of drug. 
6. Must be obtained within 4 days before treatment or re-treatment with protocol therapy. 
CBC/Differential/Platelets, creatinine and LFTs (bilirubin, AST, ALT) and phosphate must be result prior 
to initiating treatment with dasatinib at the start of each cycle. 
7. Performed at time patient officially goes off-treatment due to disease progression or toxicity. 
8. Should be performed on Cycle 2, Day 1. If QTc interval is ≤ 480 msec, ECGs are not required to be 
repeated in subsequent cycles except as clinically indicated. If the QTc interval is >480 msec, follow 
guidelines in Section 6.0. 
9. Repeat chest imaging is required regardless of whether patient had chest involvement by tumor at baseline. 
Performed on same schedule as radiographic disease assessment. 
 
 
7.2 
CENTRAL PATHOLOGY REVIEW 
 
Pathology slides are required for central review by the GOG Pathology 
Committee.  Central pathology review by a panel of three pathologists will take 
place after registration and initiation of treatment. At least one representative 
stained slide (or slides) documenting the primary tumor must be submitted (unless 
slides have been disposed of by the pathology laboratory).  In addition, 
representative immunohistochemical studies of ER and WT-1 must be submitted 
to document lack of immuno-reactivity (unless slides/blocks have been disposed 
of by the pathology laboratory).  If the primary tumor had less than 50% clear cell 
histomorphology (or if slides of the primary tumor are not available for review), 
at least one representative stained histology slide to document recurrent or 
persistent disease must be submitted along with the negative 
immunohistochemical slides for ER and WT-1 performed on the 
recurrent/persistent biopsy specimen. A biopsy of the recurrent or persistent 
tumor is required to confirm at least 50% clear cell histomorphology. The 
percentage of involvement must be documented in the pathology report or in an 
addendum to the original report. When submitting pathology material to the GOG 
SDC, individual slides must be labeled with GOG Patient ID, patient initials, 
accession number and cut (i.e. A1, 2b, 34 etc.), and packed in plastic slide 
cassettes.  Tape plastic slide cassettes shut and wrap in bubble wrap or another 
type of padded material prior to shipping.  Please include the GOG Patient ID, 
patient initials, and protocol number on all pages of the pathology report and 
black out the patient’s name. Ship pathology slides and two copies of the official 
pathology report directly to: 
 
   
Pathology Materials Coordinator 
  
GOG Statistical and Data Center 
 


GOG-0283 
 
38 
 
  
Roswell Park Cancer Institute 
  
Research Studies Center 
  
Elm and Carlton Streets 
  
Buffalo, New York 14263 
  
Phone: (716) 845-570 
 
 
7.3  
Translational Research 
 
7.31 
Specimen Requirements (11/2/15) 
 
If the patient gives permission for her specimens to be collected and used 
for this optional translational research component, then participating 
institutions are required to submit the patient’s specimens as outlined 
below (unless otherwise specified). 
 
A detailed description of the translational research specimen requirements 
and procedures can be found in Appendix VI. 
 
Required Specimen 
(Specimen Code) 
Collection Time Point 
Ship To 
FFPE Primary Tumor (FP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to any treatment 
 
Preferred FFPE 
GOG Tissue Bank within 1 
week of registration1 
FFPE Metastatic Tumor (FM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to any treatment 
 
Optional if FP01, FRP01, FRM01, 
FPP01, or FPM01 is submitted 
FFPE Recurrent Primary Tumor 
(FRP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, FRM01, 
FPP01, or FPM01 is submitted 
FFPE Recurrent Metastatic Tumor 
(FRM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, FRP01, FPP01 
, or FPM01 is submitted 
FFPE Persistent Primary Tumor 
(FPP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, FRP01, 
FRM01, or FPM01is submitted 
FFPE Persistent Metastatic Tumor 
(FPM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, FRP01, 
FRM01, or FPP01 is submitted 
Whole Blood (WB01) 
7-10mL drawn into purple top (EDTA) 
tube(s) 
Prior to or after starting study treatment 
GOG Tissue Bank the day the 
specimen is collected1 
* A copy of the corresponding pathology report must be shipped with all tissue specimens sent to the GOG tissue Bank 


GOG-0283 
 
39 
 
1 GOG Tissue Bank / Protocol GOG-0283, Nationwide Children’s Hospital, 700 Children’s Drive, WA1340, Columbus, OH 
43205, Phone: (614) 722-2865, FAX: (614) 722-2897, email: GOGBank@nationwidechildrens.org 
 
7.32 
Laboratory Testing 
 
7.321 ARID1A Mutation Analysis 
 
FFPE and DNA isolated from whole blood will be used for next 
generation sequencing with a focus on ARID1A mutation status, clear cell 
ovarian and endometrial cancer “hotspots” (e.g., PIK3CA, KRAS, 
CTNNB1, PPP2R1A0), and targets of dasatinib (e.g., CSF-1R, SRC, 
FMS, EPHA1, PDGFβ). Because these tests will be done in a research 
laboratory, the results will not be returned to patients. 
 
7.33 
Future Research 
 
Details regarding the banking and use of specimens for future research can be 
found in Appendix VI. 


GOG-0283 
 
40 
 
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 
Definitions 
 
Evaluable for toxicity.  All patients will be evaluable for toxicity from the 
time of their first treatment on study. 
 
Evaluable for objective response.  Only those patients who have 
measurable disease present at baseline, have received at least one cycle of 
therapy, and have had their disease re-evaluated will be considered 
evaluable for response.  These patients will have their response classified 
according to the definitions stated below.  (Note:  Patients who exhibit 
objective disease progression prior to the end of cycle 1 will also be 
considered evaluable.) 
 
Evaluable Non-Target Disease Response.  Patients who have lesions 
present at baseline that are evaluable but do not meet the definitions of 
measurable disease, have received at least one cycle of therapy, and have 
had their disease re-evaluated will be considered evaluable for non-target 
disease.  The response assessment is based on the presence, absence, or 
unequivocal progression of the lesions.  
 
 
8.12 
Disease Parameters 
 
Measurable disease.  Measurable lesions are defined as those that can be 
accurately measured in at least one dimension (longest diameter to be 
recorded) as >20 mm by chest x-ray, as >10 mm with CT scan, or >10 mm 
with calipers by clinical exam.  All tumor measurements must be recorded 
in millimeters (or decimal fractions of centimeters). 
 
Note:  Tumor lesions that are situated in a previously irradiated area 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. Thus, a confirmed biopsy in an irradiated 
area at a date longer than 90 days post-completion of radiation can be 
considered a target lesion to assess progression and response. 
 


GOG-0283 
 
41 
 
Malignant lymph nodes.  To be considered pathologically enlarged and 
measurable, a lymph node must be >15 mm in short axis when assessed by 
CT scan (CT scan slice thickness recommended to be no greater than 5 
mm).  At baseline and in follow-up, only the short axis will be measured 
and followed. 
 
Non-measurable disease.  All other lesions (or sites of disease), including 
small lesions (longest diameter <10 mm or pathological lymph nodes with 
≥ 10 to <15 mm short axis), are considered non-measurable disease.  Bone 
lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonitis, inflammatory breast disease, and 
abdominal masses (not followed by CT or MRI), are considered as non-
measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically defined 
simple cysts should not be considered as malignant lesions (neither 
measurable nor non-measurable) since they are, by definition, simple 
cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered 
as measurable lesions, if they meet the definition of measurability 
described above. However, if non-cystic lesions are present in the same 
patient, these are preferred for selection as target lesions. 
 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per 
organ and 5 lesions in total, representative of all involved organs, should 
be identified as target lesions and recorded and measured at baseline.  
Target lesions should be selected on the basis of their size (lesions with 
the longest diameter), be representative of all involved organs, but in 
addition should be those that lend themselves to reproducible repeated 
measurements.  It may be the case that, on occasion, the largest lesion 
does not lend itself to reproducible measurement in which circumstance 
the next largest lesion which can be measured reproducibly should be 
selected.  A sum of the diameters (longest for non-nodal lesions, short axis 
for nodal lesions) for all target lesions will be calculated and reported as 
the baseline sum diameters.  If lymph nodes are to be included in the sum, 
then only the short axis is added into the sum.  The baseline sum diameters 
will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease. 
 
Non-target lesions.  All other lesions (or sites of disease) including any 
measurable lesions over and above the 5 target lesions should be identified 
as non-target lesions and should also be recorded at baseline.  
Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted 
throughout follow-up.  


GOG-0283 
 
42 
 
 
 
 
8.13 
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.   
 
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, 
and temporal resolution; however, there are many image acquisition 
variables involved in MRI, which greatly impact image quality, lesion 
conspicuity, and measurement.  Furthermore, the availability of MRI is 
variable globally.  As with CT, if an MRI is performed, the technical 
specifications of the scanning sequences used should be optimized for the 
evaluation of the type and site of disease.  Furthermore, as with CT, the 
modality used at follow-up should be the same as was used at baseline and 
the lesions should be measured/assessed on the same pulse sequence.  It is 
beyond the scope of the RECIST guidelines to prescribe specific MRI 
pulse sequence parameters for all scanners, body parts, and diseases.  
Ideally, the same type of scanner should be used and the image acquisition 
protocol should be followed as closely as possible to prior scans.  Body 
scans should be performed with breath-hold scanning techniques, if 


GOG-0283 
 
43 
 
possible. 
 
PET-CT: At present, the low dose or attenuation correction CT portion of 
a combined PET-CT is not always of optimal diagnostic CT quality for 
use with RECIST measurements.  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. 
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and 
should not be used as a method of measurement.  Ultrasound examinations 
cannot be reproduced in their entirety for independent review at a later 
date and, because they are operator dependent, it cannot be guaranteed that 
the same technique and measurements will be taken from one assessment 
to the next.  If new lesions are identified by ultrasound in the course of the 
study, confirmation by CT or MRI is advised.  If there is concern about 
radiation exposure at CT, MRI may be used instead of CT in selected 
instances. 
 
Endoscopy, Laparoscopy: The utilization of these techniques for objective 
tumor evaluation is not advised.  However, such techniques may be useful 
to confirm complete pathological response when biopsies are obtained or 
to determine relapse in trials where recurrence following complete 
response (CR) or surgical resection is an endpoint. 
 
CA125 (Ovarian, fallopian tube and primary peritoneal cancer trials): 
CA125 alone cannot be used to assess response.  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 which are to be integrated with 
objective tumor assessment for use in first-line trials in ovarian cancer 
[JNCI 92:1534-1535, 2000]. 
 
Cytology, Histology: These techniques can be used to differentiate 
between partial responses (PR) and complete responses (CR) in rare cases 
(e.g., residual lesions in tumor types, such as germ cell tumors, where 
known residual benign tumors can remain). 
 
 
 The cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment when the measurable tumor has met 
criteria for response or stable disease is mandatory to differentiate between 
response or stable disease (an effusion may be a side effect of the 
treatment) and progressive disease. 


GOG-0283 
 
44 
 
 
 
 
 
 
 
8.14 
Response Criteria 
 
 
 
 
8.141  
Evaluation of Target Lesions 
 
Complete Response (CR): Disappearance of all target lesions.  
Any pathological lymph nodes (whether target or non-target) 
must have reduction in short axis to <10 mm. 
 
 
 
 
 
 
 
 
Partial Response (PR): At least a 30% decrease in the sum of 
the diameters of target lesions, taking as reference the baseline 
sum diameters. 
 
Progressive Disease (PD): At least a 20% increase in the sum 
of the diameters of target lesions, taking as reference the 
smallest sum on study (this includes the baseline sum if that is 
the smallest on study).  In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of at 
least 5 mm.  (Note:  the appearance of one or more new lesions 
is also considered progressions). 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for 
PR nor sufficient increase to qualify for PD, taking as reference 
the smallest sum diameters while on study. 
 
 
 
 
8.142  
Evaluation of Non-Target Lesions 
 
Complete Response (CR): Disappearance of all non-target 
lesions and normalization of tumor marker level.  All lymph 
nodes must be non-pathological in size (<10 mm short axis). 
 
Note:  If CA125 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) and/or maintenance of CA125 level above the normal 
limits. 
 
Progressive Disease (PD): Appearance of one or more new 
lesions and/or unequivocal progression of existing non-target 
lesions.  Unequivocal progression should not normally trump 
target lesion status.  It must be representative of overall disease 
status change, not a single lesion increase. 
 


GOG-0283 
 
45 
 
Although a clear progression of “non-target” lesions only is 
exceptional, the opinion of the treating physician should 
prevail in such circumstances, and the progression status 
should be confirmed at a later time by the review panel (or 
Principal Investigator). 
  
8.143  Progression Based on Serum CA-125 
 
1. Patients with elevated CA-125 pretreatment and 
normalization of CA-125 must show evidence of CA-125 
greater than or equal to two times the upper normal limit on 
two occasions at least one week apart 
OR 
2. Patients with elevated CA-125 pretreatment, which never 
normalizes must show evidence of CA-125 greater than or 
equal to two times the nadir value on two occasions at least one 
week apart 
OR 
3. Patients with CA-125 in the normal range pretreatment must 
show evidence of CA-125 greater than or equal to two times 
the upper normal limit on two occasions at least one week apart 
 
When disease progression is defined by CA-125 criteria 
alone, imaging using the same modality and encompassing 
the same field as in the initial pretreatment evaluation 
should be obtained within 2 weeks that such progression is 
documented. The patient should continue therapy, as per 
protocol, until progressive disease is documented by 
imaging. 
 
 
 
 
8.144  
Evaluation of Best Overall Response 
 
The best overall response is the best response recorded from 
the start of the treatment until disease progression/recurrence 
(taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The 
patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-
CR/Non-PD 
No 
PR 
 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 


GOG-0283 
 
46 
 
PR 
Non-
CR/Non-
PD/not 
evaluated 
No 
PR 
SD 
Non-
CR/Non-
PD/not 
evaluated 
No 
SD 
documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
*      See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
**    Only for non-randomized trials with response as primary endpoint. 
***  In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
 
Note: 
Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
reported as “symptomatic deterioration.”  Every effort should be made to document 
the objective progression even after discontinuation of treatment. 
 
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is 
increasingly used as an endpoint for assessment of efficacy in some trials so to assign this 
category when no lesions can be measured is not advised 
 
 
 
8.15 
Duration of Response 
 
Duration of overall response:  The duration of overall response is 
measured from the time measurement criteria are met for CR or PR 
(whichever is first recorded) until the first date that recurrent or 
progressive disease is objectively documented (taking as reference for 
progressive disease the smallest measurements recorded since the 
treatment started). 
 
The duration of overall CR is measured from the time measurement 
criteria are first met for CR until the first date that progressive disease is 
objectively documented.  
 
Duration of stable disease:  Stable disease is measured from the start of the 
treatment until the criteria for progression are met, taking as reference the 
smallest measurements recorded since the treatment started, including the 
baseline measurements.  


GOG-0283 
 
47 
 
 
 
8.16 
Progression-Free Survival 
 
Progression-Free Survival (PFS) is defined as the duration of time from 
start of treatment to time of progression or death, whichever occurs first. 
 
 
8.17 
Survival 
Survival is defined as the duration of time from start of treatment to time 
of death or the date of last contact. 


GOG-0283 
 
48 
 
9.0 
DURATION OF STUDY    
 
 
9.1  
Patients will continue on study until disease progression or adverse effects  
 
prohibit further treatment. 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 or study withdrawal. Patients will then be 
followed (with physical exams and histories) 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 follow-up 
forms submitted via Medidata Rave unless consent is withdrawn. 
 
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 Cycle Drug 
Information Forms and adverse events on Toxicity forms until the patient 
qualifies as being off study therapy 
 
 


GOG-0283 
 
49 
 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES   
 
10.1 
ADVERSE EVENT REPORTING FOR AN INVESTIGATIONAL AGENT 
   
10.11 Definition of Adverse Events (AE) 
 
An adverse event (AE) is any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease that occurs in a 
patient administered a medical treatment, whether the event is considered 
related or unrelated to the medical treatment.  
 
CTCAE term (AE description) and grade:  The descriptions and 
grading scales found in the CTEP Active Version of the NCI Common 
Terminology Criteria for Adverse Events (CTCAE) will be utilized for AE 
reporting.  The CTEP Active Version of the CTCAE is identified and 
located on the CTEP website at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.ht
m.  All appropriate treatment areas should have access to a copy of the 
CTEP Active Version of CTCAE. 
 
The CTCAE 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 adverse reactions 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 Phase 1 and Early Phase 2 Studies:  Expedited Reporting  
Requirements for Adverse Events that Occur on Studies under an 
IND/IDE within 30 Days of the Last Administration of the Investigational 
Agent/Intervention 1, 2 


GOG-0283 
 
50 
 
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 and Grade 2 Timeframes 
Grade 3-5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 Calendar 
Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
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; 5 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 5 calendar days of the initial 24-hour report. 
o 
“10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 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 5 calendar days for: 
• 
All Grade 3, 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• 
Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
2For 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. 
Effective Date:  May 5, 2011 
Note:  All deaths on study require both routine and expedited reporting regardless  
of causality.   Attribution to treatment or other cause must be provided. 
 
• 
Expedited AE reporting timelines defined: 
➢ “24 hours; 3 calendar days” – The investigator must initially report the AE via 
AdEERS within 24 hours of learning of the event followed by a complete AdEERS 
report within 3 calendar days of the initial 24-hour report. 
➢ “7 calendar days” - A complete AdEERS report on the AE must be submitted within  
7 calendar days of the investigator learning of the event.  
 


GOG-0283 
 
51 
 
• 
Any medical event equivalent to CTCAE grade 3, 4, or 5 that precipitates hospitalization 
(or prolongation of existing hospitalization) must be reported regardless of 
attribution and designation as expected or unexpected with the exception of any 
events identified as protocol-specific expedited adverse event reporting exclusions. 
 
• 
Any event that results in persistent or significant disabilities/incapacities, congenital 
anomalies, or birth defects must be reported via AdEERS if the event occurs following 
treatment with an agent under a CTEP IND. 
 
• 
Use the NCI protocol number and the protocol-specific patient ID provided during trial 
registration on all reports. 
Additional Instructions or Exceptions to AdEERS Expedited Reporting Requirements for Phase 
2 and 3 Trials Utilizing an Agent under a CTEP-IND: 
 
• Grades 2-4 myelosuppression (including neutropenia, anemia, and thrombocytopenia) 
that do not require hospitalization are exempt from expedited reporting 
 
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 
your 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. 
 
 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. 
 
For the purposes of expedited reporting of adverse events to CTEP, 
unexpected events are those not listed in the Agent Specific 
Adverse Event List (ASAEL). The ASAEL is a subset of AEs 
within the Comprehensive Adverse Event and Potential Risks List 
(CAEPR). This list of events is based on CTEP’s clinical 


GOG-0283 
 
52 
 
experience with this agent and defines “expected” Grade 2 and 3 
AEs not requiring hospitalization as exempt from expedited 
reporting. The CAEPR is a complete list of reported and/or 
potential AEs associated with an agent under a CTEP IND. For 
questions or comments regarding the ASAEL or CAEPR, please 
contact the AdEERS MD Help Desk at adeersmd@tech-res.com. 
 
 
 
 
10.15 Routine Adverse Event Reporting  
 
For studies using investigational agents, the GOG Statistical and Data 
Center (SDC) routinely reports adverse events electronically to the CTEP 
Clinical Data Update System (CDUS Version 3.0).  The SDC submits this 
data quarterly.  The AEs reported through AdEERS will also be included 
with the quarterly CDUS data submissions. 
 
10.2 
 GOG DATA MANAGEMENT FORMS 
 
The following forms must be completed for all patients registered and submitted 
according to the schedule below. Protocol forms with the exception F forms and 
Pathology Reports must be submitted via the Medidata Rave Electronic Data  
Entry System which is available through the GOG Web Menu page  
(www.gogstats.org). All amendments to forms submitted through Medidata Rave 
must also be submitted through Medidata Rave. Note: Pathology material (path 
report and slides) may be submitted together via postal mail. Pathology 
report can also be submitted by using the upload feature of SEDES (stained 
slides must be submitted via postal mail). 
  
Form± 
Due within 
Copies* 
Comments 
Weeks 
Event 
Specimen Consent 
Application 
1 
Registration 
N/A 
Online 
Registration Form 
2 
Registration 
N/A 
Mandatory 
Submission 
via Medidata Rave 
Visit Information – 
Baseline Form 
Pre-Study History: 
- History Information Form 
- Primary Surgery Form♦ 
- Chemotherapy 
Information Form♦ 
2 
Registration 
N/A 
Mandatory 
submission via  
Medidata Rave 
 
Pre-Treatment Summary 
Form 
4 
Registration 
N/A 
Mandatory 
submission via  
Medidata Rave 


GOG-0283 
 
53 
 
 Solid Tumor Evaluation: 
- Target Lesions Form♦ 
- Non-Target Lesions 
Form♦ 
2 
Registration 
N/A 
Mandatory 
Submission 
via Medidata Rave 
 
Primary disease: 
Pathology Report 
Stained Slides  
 
Recurrent or Persistent 
Disease: 
Pathology Report 
Stained Slides  
 
6 
6 
 
 
 
6 
6 
 
Registration 
Registration 
 
 
 
Registration 
Registration 
 
2 
** 
 
 
 
2 
** 
 
Submit together to 
SDC via postal mail 
 
 
 
Submit together to 
SDC via postal mail 
Visit Information Form 
- Cycle Patient Information 
Form 
- Cycle Drug Information 
Form 
- Labs and Chemistries 
Form 
- Vital signs Assessment 
Form 
2 
Completion of 
each cycle of 
therapy 
N/A 
Mandatory 
submission via 
Medidata Rave 
Solid Tumor Evaluation: 
- Target Lesions Form♦ 
- Non-Target Form♦ 
- New Target Lesions 
Form♦ 
- Status and Response 
Form♦ 
2 
Clinical response 
assessment 
N/A 
Mandatory 
submission via 
Medidata Rave 
Toxicity Report 
- Section 1 Form 
- NADIRS Form 
- Adverse Event Form 
- Adverse Event Grades 
2 
Beginning of each 
subsequent cycle 
N/A 
Mandatory 
submission via 
Medidata Rave 
Treatment Completion 
Form 
 
2 
Completion of 
study Rx and 
change in Rx 
N/A 
Mandatory 
submission via 
Medidata Rave 
Visit Information Follow-
Up Form 
- Follow-Up Form 
Follow-Up Period Adverse 
Event: 
- Reporting Form – Part 1♦ 
- Reporting Form – Part 2♦ 
2 
Disease 
progression; death; 
normal follow-up 
N/A 
Mandatory 
submission via 
Medidata Rave 
quarterly for 2 years, 
semi-annually for 3 
more years 
Form TR-FP01- 0283*** 
FFPE primary tumor 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 


GOG-0283 
 
54 
 
Form TR-FM01- 0283*** 
FFPE metastatic tumor 
(optional) 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
Form TR-FRP01- 0283*** 
FFPE recurrent primary 
tumor (optional) 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
Form TR-FRM01- 
0283*** 
FFPE recurrent 
metastatic tumor 
(optional) 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
Form TR-FPP01-0283*** 
FFPE persistent primary 
tumor (optional) 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
Form TR-FPM01-0283*** 
FFPE persistent metastatic 
tumor (optional) 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
Form TR-WB01- 0283 
whole blood 
1 
Registration 
N/A 
Mandatory 
submission via 
Medidata Rave 
* 
The number of required copies including the original form which must be sent to the Statistical and Data 
Center. 
** At least one representative stained slide (or slides) documenting the primary.  For recurrent or persistent disease 
submit Pathology Report, and slides only if histologically documented (See Section 7.2 for additional 
requirements).  If the primary tumor had less than 50% clear cell histomorphology, a biopsy of the recurrent or 
persistent tumor is required to confirm at least 50% clear cell histomorphology. The percentage of involvement 
must be documented in the pathology report or in an addendum to the original report. 
*** A copy of the corresponding pathology report must be shipped with all tissue specimens sent to the GOG Tissue 
Bank 
♦Appropriate forms will be loaded based on answers reported on corresponding Visit Information Forms. 
 
This study will be monitored by the Complete Clinical Data System (CDUS) Version 3.0 CDUS 
data will be submitted quarterly to CTEP by electronic means. 


GOG-0283 
 
55 
 
 
11.0 
STATISTICAL CONSIDERATIONS   
 
The primary objective of this study is to assess the efficacy of dasatinib in patients with 
recurrent or persistent ovarian, fallopian tube, primary peritoneal, or endometrial clear 
cell carcinoma. The trial will examine the effect in patients with and without loss of 
BAF250a expression. 
11.1 
Design Summary:  
This is a two-group, single arm, Phase II clinical trial that will examine the 
efficacy of the study regimen in patients with and without loss of BAF250a 
expression.  No randomization is involved. All patients will be registered via 
OPEN.  Prior to registration, eligibility will be reviewed via Eligibility check list 
verification.  All reports will include a complete accounting of all patients 
registered to this protocol. 
 
11.2 
Principal Parameters: 
 
11.21 Efficacy Endpoints 
 
11.211 Primary: The proportion of patients with objective tumor response 
rate (complete [CR] or partial [PR]). 
 
11.212 Secondary: Duration of progression-free survival and overall 
survival 
 
11.24 Adverse effects:  frequency and severity of adverse effects as assessed by 
CTCAE version 4. 
 
11.26 Translational Research Endpoints: ARID1A mutation status using next-
generation exon-capture sequencing performed in FFPE. 
 
11.3 
Accrual:  
 
GOG 0254 is an ongoing study of clear cell ovarian patients (with no restriction 
on BAF250a expression) and has accrued approximately 1 patient per month.  
This planned study includes both ovarian and endometrial cancer patients, so we 
expect about twice as many patients available for screening, and we expect 
approximately 40% of patients will have loss of BAF250a expression.  Therefore, 
we project accrual to be approximately 2 patients per month when enrolling both 
patients with and without loss of BAF250a expression, and approximately 0.5 
patients per month when enrolling only patients with loss of BAF250a expression 
 
Each stage of accrual is expected to take approximately 24 months.  
 


GOG-0283 
 
56 
 
11.4 
Primary Hypothesis, Sample Size, and Design 
The primary hypothesis of this study tests the proportion of patients with 
objective tumor response. There are no historical data available on what the 
response rate is in this patient population, so we will test whether the response 
rate is indicative of treatment activity for the agent in this patient population. We 
will test the null hypothesis (H0) that the objective response rate is 10% or less 
against the alternative (H1) that it is greater than 10% assuming the true response 
rate for the agent is 30%. 
 
The guiding principle in selecting the design for this study is to limit the number 
of patients treated with clinically ineffective therapies but to estimate efficacy 
with reasonable precision for those agents that are clinically active. 
 
Within each BAF250a group, the optimal, flexible design of Chen and Ng will 
be used.  The first stage of this study will target an accrual of 15 eligible patients, 
but in practice will permit accrual to range from 11 to 18 patients for logistical 
reasons due to managing a multicenter study. If more than 1 out of 11-17 or 2 out 
of 18 patients experience a response (complete or partial) and clinical judgment 
indicates, accrual to the second stage of the trial will be initiated. Otherwise, the 
study will be stopped and the treatment regimen will be considered unworthy of 
further evaluation in this patient population. If the study advances to the second 
stage then an overall study accrual of 28 patients will be targeted, but the actual 
accrual will be permitted to range from 24 to 31 patients. If more than 3 out of 24, 
or 4 out of 25-28, or 5 out of 29-31 patients experience a response (complete or 
partial) then the regimen will be considered worthy of additional investigation in a 
subsequent study. If the true response rate is 10% (H0), these decision rules limit 
the average probability of wrongly designating the treatment as active to 10% 
(type I error), and the average probability of stopping after completing the first 
stage of accrual is 61%. On the other hand, if the true response rate is 30% (H1) 
then the average probability of correctly classifying the treatment as active is 
90%. The probability of type I error and the statistical power in this design are 
average probabilities and were computed from the individual probabilities 
averaged over all permitted accrual combinations and assuming each combination 
is equally likely. 
 
We target alpha and beta errors of 0.10 within each patient group without 
adjustment for multiplicity due to the rare nature of this disease in order to 
maintain reasonable sample sizes. 
 
Due to the expected activity in the patients with loss of BAF250a expression, if 
the first stage results indicate a second stage in patients without loss but do not 
indicate a second stage in patients with loss, both groups will be enrolled in Stage 
2. 
 


GOG-0283 
 
57 
 
The following table summarizes the accrual and decision guidelines for this study: 
Stage of 
Accrual 
Targeted 
Cumulative 
Accrual 
Limits of 
Actual Accrual 
Reject H1 (Reject Drug) if 
Response Rate ≤Ri/Ni 
1 
15 
11-18 
1/(11-17), 2/18 
2 
28 
24-31 
3/24, 4/(25-28), 5/(29-31) 
Ri: cumulative number of responses in stage i, i=1, 2. 
Ni: cumulative number of subjects in stage i, i=1, 2. 
 
11.5 
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 "unknown". This category will be 
listed and be reflected in the calculation of the response rate. 
 
11.6 
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, 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 Data Safety and Monitoring Board (DSMB) 
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) within two working days 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 Data and Safety 
Monitoring Board. However, patients currently receiving treatment may continue 


GOG-0283 
 
58 
 
to receive treatment in accordance protocol guidelines at the discretion of their 
physicians, unless directed otherwise.  
 
11.7 
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. 
 
The frequency of ARID1A mutation status using next-generation exon-capture 
sequencing performed in FFPE will be tabulated to determine the correlation 
between BAF250a IHC and ARID1A mutations (NB: technology in translational 
research is rapidly progressing and subject to change.) 
 
11.8 
Anticipated Gender and Minority Inclusion:   
This study restricts entry to women by nature of the site of disease.  The table 
below lists the projected numbers of patients by racial/ethnic subgroup in a total 
of 81 patients (the maximum potential, planned sample size).  There is no data 
that support differences in the intervention effect between racial/ethnic 
subgroups.  Therefore, the study design does not involve race.  
 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
 
5 
+ 
0 
=  
5 
Not Hispanic or Latino 
 
57 
+ 
0 
=  
57 
Ethnic Category: Total of all subjects  
62 
+ 
0 
=  
62 
Racial Category 
 
American Indian or Alaskan Native 
 
1 
+ 
0 
=  
1 
Asian 
 
1 
+ 
0 
=  
1 
Black or African American 
 
2 
+ 
0 
=  
2 
Native Hawaiian or other Pacific Islander  
1 
+ 
0 
=  
1 
White 
 
57 
+ 
0 
=  
57 
Racial Category: Total of all subjects 
 
62 
+ 
0 
=  
62 
 


GOG-0283 
 
59 
 
12.0 
BIBLIOGRAPHY   
 
 
1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating 
socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 
61(4): 212-36. 
 
2. Mackay HJ, Brady MF, Oza AM, et al. Prognostic relevance of uncommon ovarian 
histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer 
2010; 20(6): 945-52. 
 
3. Winter WE, 3rd, Maxwell GL, Tian C, et al. Prognostic factors for stage III epithelial 
ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25(24): 3621-
7. 
 
4. Sugiyama T, Kamura T, Kigawa J, et al. Clinical characteristics of clear cell carcinoma of 
the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based 
chemotherapy. Cancer 2000; 88(11): 2584-9. 
 
5. Vaughan S, Coward JI, Bast RC, Jr., et al. Rethinking ovarian cancer: recommendations 
for improving outcomes. Nat Rev Cancer 2011; 11(10): 719-25. 
 
6. Ness RB. Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Am J 
Obstet Gynecol 2003; 189(1): 280-94. 
 
7. Vigano P, Somigliana E, Chiodo I, Abbiati A, Vercellini P. Molecular mechanisms and 
biological plausibility underlying the malignant transformation of endometriosis: a 
critical analysis. Human reproduction update 2006; 12(1): 77-89. 
 
8. Wiegand KC, Shah SP, Al-Agha OM, et al. ARID1A mutations in endometriosis-
associated ovarian carcinomas. N Engl J Med 2010; 363(16): 1532-43. 
 
9. Guan B, Wang TL, Shih Ie M. ARID1A, a factor that promotes formation of SWI/SNF-
mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer 
Res 2011; 71(21): 6718-27. 
 
10. Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. Loss of ARID1A protein 
expression occurs as an early event in ovarian clear-cell carcinoma development and 
frequently coexists with PIK3CA mutations. Mod Pathol 2012; 25(4): 615-24. 
 
11. Katagiri A, Nakayama K, Rahman MT, et al. Loss of ARID1A expression is related to 
shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. 
Mod Pathol 2012; 25(2): 282-8. 
 
12. Miller R, Brough R, Bajrami I, Kaye SB, Lord CJ, Ashworth A. Functional profiling of 
clear cell ovarian cancer. ASCO Meeting Abstracts 2012; 30(15_suppl): 5035. 


GOG-0283 
 
60 
 
 
13. Kluger HM, Dolled-Filhart M, Rodov S, Kacinski BM, Camp RL, Rimm DL. 
Macrophage colony-stimulating factor-1 receptor expression is associated with poor 
outcome in breast cancer by large cohort tissue microarray analysis. Clin Cancer Res 
2004; 10(1 Pt 1): 173-7. 
 
14. Mashkani B, Griffith R, Ashman LK. Colony stimulating factor-1 receptor as a target for 
small molecule inhibitors. Bioorganic & medicinal chemistry 2010; 18(5): 1789-97. 
 
15. Wagle N, Berger MF, Davis MJ, et al. High-throughput detection of actionable genomic 
alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer 
discovery 2012; 2(1): 82-93. 
 
16. Chen TT and NG T. Optimal flexible designs in phase II clinical trials. Statistics in 
Medicine 1998;17:2301-12 
 
17. Hunter, T.  (1997). Oncoprotein networks.  Cell.  88:333-346. 
 
18. Investigator's Brochure.  (2010). Dasatinib.  BMS-354825.  Bristol-Myers Squibb. 
Version No:  10.  Version Date:  November 2010.  
 
19. Lombardo, L.J., F.Y. Lee, P. Chen, et al.  (2004). Discovery of N-(2-chloro-6-methyl-
phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-
5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor 
activity in preclinical assays.  J Med Chem. 47:6658-6661. 
 
20. Demetri, G.D., P. Lo Russo, I.R.J. MacPherson, et al.  (2009)  Phase I dose-escalation 
and pharmacokinetic study of dasatinib in patients with advanced solid tumors.  Clin 
Cancer Res. 15: 6232-6240. 
 
21. Li S., Y. Hu, S.J. Swerdlow, et al. (2004).  Simultaneous targeting of SRC and BCR-
ABL kinases by BMS-354825 cures Ph+ acute lymphoblastic leukemia in mice.  Blood.  
104: Abstr. 1976. 
 
22. Schittenhelm, M., S. Shiraga, F.Y. Lee, and M.C. Heinrich.  (2006). Dasatinib (BMS-
354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, 
juxtamembrane, and activation loop mutant KIT isoforms associated with human 
malignancies.  Cancer Res. 66: 473-481. 
 
23. Wu, J.Y., N.J. Donato, D.S. Hong, et al.  (2004). The SRC/ABL kinase inhibitor BMS-
354825 induces apoptosis and overcomes imatinib resistance in chronic myelogenous 
leukemia cell lines and patient specimens.  Proc Am Assoc Can Res.  45:A3850. 
 
24. Hochhaus, A., and T. Hughes.  (2004). Clinical resistance to imatinib:  Mechanisms and 
implications.  Hematol Oncol Clin North Amer 18:641-656. 
 


GOG-0283 
61 
 
25. Donato, N.J., J. Wu, L.Y. Kong, et al.  (2004). The SRC/ABL inhibitor BMS-354825 
overcomes resistance to imatinib mesylate in chronic myelogenous leukemia cells 
through multiple mechanisms.  Blood.  104:A1989. 
 
26. Lee, F.Y., L. Lombardo, R. Borzilleri, et al.  (2004). BMS-354825 - A potent dual 
SRC/ABL kinase inhibitor possessing curative efficacy against imatinib sensitive and 
resistant human CML models in vivo.  Proc Am Assoc Cancer Res.  45:A3987. 
 
27. Shah, N.P.  (2005). Loss of response to imatinib:  Mechanisms and management.  
Hematol.  183-187. 
 
28. Shah, N.P., F.Y. Lee, R. Luo, et al.  (2005). Dasatinib (BMS-354825) inhibits KITD816V, 
an imatinib-resistant activating mutation that triggers neoplastic growth in the majority of 
patients with systemic mastocytosis.  Blood.  108:286-291. 
 
29. Shah, N.P., C. Tran, F.Y. Lee, and C.L. Sawyers.  (2004). BMS-354825 is a novel orally 
bioavailable small molecule ABL tyrosine kinase inhibitor that successfully and safely 
inhibits the kinase activity of multiple imatinib-resistant BCR-ABL isoforms in vitro and 
in vivo.  Proc Am Assoc Can Res.  45:A5624. 
 
30. Talpaz, M., N.P. Shah, H. Kantarjian, et al.  (2006)  Dasatinib in imatinib-resistant 
Philadelphia chromosome-positive leukemias.  N Engl J Med.  354:2531-2541.  
 
31. Tokarski, J.S., J. Newitt, F.Y. Lee, et al.  (2004). The crystal structure of Abl kinase with 
BMS-354825, a dual SRC/ABL kinase inhibitor.  Blood.  104:A553. 
 
32. Johnson, F.M., B. Saigal, M. Talpaz, and N.J. Donato.  (2005).  BMS-354825 tyrosine 
kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head 
and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) 
cells.  Clin Cancer Res.  11:6924-6932. 
 
33. Luo F.R., Z. Yang, A. Camuso, et al.  (2005)  Pharmacodynamic biomarker.  Proc Am 
Assoc Cancer Res. 46:A4183. 
 
34. Sawyers, C.L., N.P. Shah, H.M. Kantarjian, et al.  (2005). A phase I study of BMS-
354825 in patients with imatinib-resistant and intolerant accelerated and blast phase 
chronic myeloid leukemia (CML):  Results from CA180002.  Proc Am Soc Clin Oncol.  
24:A6520. 
 
35. Chen, T.T. and T. H. Ng (1998). Optimal flexible designs in phase II clinical trials. 
Statistics in Medicine 17(20): 2301-2312. 


GOG-0283 
62 
 
Appendix I - NCI/DCTD Standard Protocol Language 
 
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) contained 
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 


GOG-0283 
63 
 
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. 
 
 


GOG-0283 
64 
 
 
APPENDIX II - NRG Oncology General Therapy Guidelines (11/2/15) 
 
• For 21 or 28 day cycles, a patient will be permitted to have a new cycle of 
therapy 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 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 doses to be delivered 
within a “24-hour window,” for example; “Day 8 therapy” can be delivered on 
Day 7, Day 8, or Day 9 and “Day 15 therapy” can be given on Day 14, Day 15, or 
Day 16. 
• 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). 
• 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 less than 10% weight changes. 


GOG-0283 
65 
 
Appendix III - Patient Medication Calendar 
 
A PHASE II TRIAL OF DASATINIB (NSC #732517) IN RECURRENT /PERSISTENT 
OVARY, FALLOPIAN TUBE, PRIMARY PERITONEAL AND ENDOMETRIAL CLEAR 
CELL CARCINOMA WITH LOSS OF BAF250a EXPRESSION 
 
 
This is a calendar on which you are to record the number of dasatinib tablets you take each day.  
The instructions on how to take the dasatinib are below.  
 
Use the calendar to record date, time and number of dasatinib tablets taken each day.  You will 
start by taking 140 mg (two 50mg tablets and two 20mg tablets) of dasatinib once each day for 
28 days. This 28 day time period is called a cycle. It is possible your doctor may reduce the 
amount of dasatinib you take while participating in this study.  Your doctor will discuss the new 
treatment plan with you at that time. Medication should be taken as instructed without skipping 
any medications.  If you have missed a dose please mark down as “0” on the # slot for that day.  
If your doctor changes the amount of dasatinib you take, please be sure to write down the correct 
number of pills and correct amount taken in the columns below. 
 
Dasatinib can be taken with or without a meal, but should be swallowed with at least 8 
ounces (240 mL) of water. A light meal is not required, but may improve stomach upset 
from dasatinib.  Tablets must be swallowed whole and may not be broken. Dasatinib can be 
taken in the morning or evening but should be taken at approximately the same time each 
day.  
 
You should not take H2 blockers or proton pump inhibitors while on this study. You can 
take certain antacid medications 2 hours prior to or 2 hours after taking dasatinib. Please 
ask your study doctor if you think you are taking one of these medications. 
 
Note to staff:  Please give patient a drug log at initial enrollment and every week 4 visit.  Instruct patient 
how to complete the diary log.  If they are taking the first pill at a visit complete the log with them.  
Remind them they must bring the log back at each visit along with pill bottles, empties included. 
 
 
Please note: Medication Calendar should be brought to each appointment 
along with medication bottles (empty included). 
 
 
PATIENT MEDICATION CALENDAR 
 
Patient Name________________________________  Patient Study ID____________ 
 
Total Daily Dose: ___ 50mg tablets, ___ 20mg tablets 
 
Day 
Date 
Time 
# of 50mg tablets 
# of 20mg tablets 
Comments 


 
 
GOG-0283 
 
66 
 
1  
 
 
 
 
 
2  
 
 
 
 
 
3  
 
 
 
 
 
4  
 
 
 
 
 
5  
 
 
 
 
 
6  
 
 
 
 
 
7 
 
 
 
 
 
8  
 
 
 
 
 
9 
 
 
 
 
 
10  
 
 
 
 
 
11 
 
 
 
 
 
12 
 
 
 
 
 
13 
 
 
 
 
 
14  
 
 
 
 
 
15 
 
 
 
 
 
16  
 
 
 
 
 
17 
 
 
 
 
 
18  
 
 
 
 
 
19 
 
 
 
 
 
20  
 
 
 
 
 
21 
 
 
 
 
 
22 
 
 
 
 
 
23 
 
 
 
 
 
24 
 
 
 
 
 
25 
 
 
 
 
 
26 
 
 
 
 
 
27 
 
 
 
 
 
28 
 
 
 
 
 
 
 
Patient Signature ___________________________________   Date _________________ 
 
Physician’s Office will complete this section:  
1. Date patient started protocol treatment____________________________________________________ 
2. Date patient started this cycle _________________         This is cycle #__________ 
3. Patient’s planned total daily dose for this cycle_____________________  
4. Total number of tablets taken this month__________________________________________________ 
5. Number or pills returned/unused this month ________________________________________________ 
6. Physician/Nurse/Data Manager’s Signature_________________________________________________ 
 


 
 
GOG-0283 
 
67 
 
Appendix IV - BAF250a IMMUNOHISTOCHEMISTRY TESTING 
 
An appropriate tumor specimen from each patient must be submitted to Memorial Sloan-
Kettering Cancer Center, Department of Pathology, and tested for BAF250a by 
immunohistochemistry (IHC). Patients must sign an approved informed consent to 
participate in the testing and treatment components of this study. 
 
1.   SLIDE REQUIREMENTS 
 
Only one tumor specimen is required to test for BAF250a by IHC. If more than one 
tumor specimen is available, the more advanced and most recently obtained specimen 
should be submitted (e.g., a metastatic lesion rather than a primary; recurrent or 
persistent tumor rather than a primary or metastatic tumor from a previously untreated 
patient). There must be clear cell carcinoma AND normal tissue present on the 
slides. 
 
Five (minimum four) unstained sections (charged, 4-6µm) must be shipped to 
Memorial Sloan-Kettering Cancer Center, Department of Pathology (address below) 
within 7 days of cutting the slides. 
 
 
3.   LABELING SLIDES 
 
Label each individual slide with the Screening Patient Identifier. Slides may also be 
labeled with the pathology accession and block number, but these identifiers are not 
required. Do not label slides with any personal identifying information (e.g., patient 
name, patient initials, date of birth). 
 
4.   SHIPPING SLIDES 
 
Complete the GOG-0283 BAF250a Immunohistochemistry Requisition (Appendix 
V). Please be sure the Screening Patient Identifier on the slides matches the Screening 
Patient Identifier on the requisition. 
 
Ship the slides along with a de-identified copy of the corresponding pathology report 
to: 
 
ATTN: Jessica Menzel 
Memorial Sloan-Kettering Cancer Center 
Department of Pathology 
1275 York Ave 
New York, NY 10065 
Phone: 212-639-7297 
Fax: 646-422-2070 
Email: menzelj@mskcc.org 
 


 
 
GOG-0283 
 
68 
 
5.   BAF250a IHC TESTING PROCEDURES 
 
One slide will be stained for BAF250a (Sigma, St. Louis) and one with hematoxylin 
and eosin (H&E). The H&E will confirm that there is normal tissue present on the 
slide to serve as a normal control. The slides will be reviewed by a gynecologic 
pathologist. 
 
The test result will be considered positive (RETAINED) if any of the tumor nuclei are 
immunoreactive and negative (LOSS) if all tumor nuclei show no staining. The result 
will be interpreted as a technical failure and subsequently repeated on an additional 
slide if the normal tissue shows no immunoreactivity. 
 
 
6.   REPORTING BAF250a IHC TESTING RESULTS 
 
BAF250a IHC will be reported as either RETAINED or LOSS. Result reporting may 
be delayed if a discrepancy occurs or if required information is missing on the 
requisition. 
 
Memorial Sloan-Kettering Cancer Center staff will be responsible for conveying the 
results to the GOG Statistical and Data Center, at which point, if the trial is open to 
patients with resulting BAF250a expression status, the patient can then be registered 
on trial. For the portion of the study where patients may be enrolled regardless of 
BAF250a IHC status, the result of this testing will not be communicated back to the 
GOG Institution where the testing was sent. This will be done to minimize the chance 
of bias for investigator assessed response assessments.  
 
 


 
 
GOG-0283 
 
69 
 
Appendix V - BAF250a IMMUNOHISTOCHEMISTRY REQUISITION 
 
PROTOCOL GOG-0283: A PHASE II TRIAL OF DCTD-SPONSORED DASATINIB (NSC 
#732517 IND # 73969) IN RECURRENT /PERSISTENT OVARY, FALLOPIAN TUBE, 
PRIMARY PERITONEAL, AND ENDOMETRIALCLEAR CELL CARCINOMA 
CHARACTERIZED FOR THE RETENTION OR LOSS OF BAF250a EXPRESSION 
 
TO: 
ATTN: Jessica Menzel 
Memorial Sloan-Kettering Cancer Center 
Department of Pathology 
1275 York Ave 
New York, NY 10065 
Phone: 212-639-7297 
Fax: 646-422-2070 
Email: menzelj@mskcc.org 
FROM: 
Institution: ______________________________ 
GOG Site Number: ________________________ 
C/O: ___________________________________ 
Address:________________________________ 
_______________________________________ 
Fax: __________________________________ 
Phone: _________________________________ 
Date Sent: ______________________________ 
 
GOG Patient ID (De-Identified): _____________________________ 
 
Primary Tumor Site: 
□ Ovary 
□ Fallopian Tube 
□ Peritoneum 
□ Endometrium 
□ Endometriosis 
 
Unstained Slides Submitted: 
 
Number: 
______________________ 
 
Thickness: 
______________________ 
 
 
*** Please include a de-identified copy of the corresponding pathology report. 
Label the pathology report with the GOG Patient ID. *** 


 
 
GOG-0283 
 
70 
 
Appendix VI - Translational Research Specimen Procedures (11/2/15)(XX/XX/XX) 
 
I. 
Summary of Translational Research Specimen Requirements 
 
If the patient gives permission for her specimens to be used for this optional 
translational research component, then participating institutions are required to 
submit the patient’s specimens as outlined below (unless otherwise specified). 
 
Required Specimen 
(Specimen Code) 
Collection Time Point 
Ship To 
FFPE Primary Tumor (FP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
Prior to all treatment 
 
Preferred FFPE 
GOG Tissue Bank within 1 week 
of registration1 
FFPE Metastatic Tumor (FM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
Prior to all treatment 
 
Optional if FP01, FRP01, 
FRM01, FPP01, or FPM01 is 
submitted 
FFPE Recurrent Primary Tumor 
(FRP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, 
FRM01, FPP01, FPM01 is 
submitted 
FFPE Recurrent Metastatic 
Tumor (FRM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
FFPE Persistent Primary Tumor 
(FPP01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, 
FRP01, FRM01, or FPM01is 
submitted 
FFPE Persistent Metastatic Tumor 
(FPM01)* 
1st Choice: block 
2nd Choice: 25 unstained slides (10 
charged, 5µm & 15 uncharged, 
10µm) 
Prior to study treatment 
 
Optional if FP01, FM01, 
FRP01, FRM01, or FPP01 is 
submitted 
Whole Blood (WB01) 
7-10mL drawn into purple top 
(EDTA) tube(s) 
Prior to or after starting study 
treatment 
GOG Tissue Bank the day the 
specimen is collected1 
* A copy of the corresponding pathology report must be shipped with all tissue specimens sent to the GOG Tissue 
Bank 
1 GOG Tissue Bank / Protocol GOG-GOG-0283, Nationwide Children’s Hospital, 700 Children’s Drive,  
WA1340, 
Columbus, OH 43205, Phone: (614) 722-2865, FAX: (614) 722-2897, Email: GOGBank@nationwidechildrens.org 
 
II. 
Obtaining a GOG Bank ID for Translational Research Specimens 
 


 
 
GOG-0283 
 
71 
 
Only one GOG Bank ID (# # # # - # # - G # # #) is assigned per patient. All 
translational research specimens and accompanying paperwork must be labeled 
with this coded patient 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’s study ID (GOG #) for all protocols with translational research 
specimen requirements before requesting a Bank ID from the Tissue Bank Portal. 
Be sure to indicate if the patient has a previous GOG # when registering. This 
will ensure that the patient is only assigned one Bank ID. The GOG ID – Bank ID 
Lookup on the Tissue Bank Portal can be used to search for an existing Bank ID. 
 
Please contact GOG User Support if you need assistance or have assigned more 
than one Bank ID to a patient (Email: support@gogstats.org; Phone: 716-845-
7767). 
 
III. Requesting Translational Research Specimen Kits 
 
Kits are not provided for this protocol. 
 
IV. Labeling Translational Research Specimens 
 
A waterproof permanent marker or printed label should be used to label each 
translational research specimen with: 
 
GOG Bank ID (# # # # - # # - G # # #) 
GOG protocol number (GOG- # # # #) 
specimen code (see section I) 
collection date (mm/dd/yyyy) 
surgical pathology accession number (tissue specimens only) 
block number (tissue specimens only) 
 
Note: If labeling slides, only label on the top, front portion of the slide. Do not place 
a label on the back of the slide or over the tissue. The label must fit on the slide and 
should not be wrapped around the slide or hang over the edge. 
 
V. 
Submitting Formalin-Fixed, Paraffin-Embedded Tissue 
 
Formalin-fixed, paraffin embedded (FFPE) tissue should be the most representative 
of the specimen type (primary, metastatic, recurrent). Primary and metastatic tumor 
should be collected prior to all treatment. Recurrent and persistent tumor should be 
collected prior to the study treatment. Recurrent or persistent tumor collected from 
the site of primary disease should be labeled recurrent primary or persistent 
primary, respectively. Recurrent or persistent tumor collected from a site other than 
the site of primary disease (e.g., lymph node) should be labeled recurrent metastatic 
or persistent metastatic, respectively. Only one block may be submitted per tissue 
type. 


 
 
GOG-0283 
 
72 
 
 
Every attempt should be made to provide a FFPE block; however, if a block cannot 
be provided on a permanent basis, then 25 unstained slides (10 charged, 5µm and 
15 uncharged, 10 µm) should be submitted. All tissue sections should be cut 
sequentially from the same block.  
 
Note: Unstained slides for screening and stained slides to confirm patient 
eligibility by central pathology review are required for this protocol, but are 
NOT sent to the GOG Tissue Bank (see protocol for details). If these slides will 
be cut from the same block that will be submitted for translational research, your 
pathology department should cut these slides prior to submitting the block for 
translational research. 
 
The type of specimen (block, slides) should be specified on Form TR. If submitting 
slides, the slide type, thickness, and count should also be specified.  
 
All FFPE tissue should be submitted with the corresponding pathology report. 
 
VI. Submitting Whole Blood 
 
1.  Label the lavender/purple top (EDTA) collection tube(s) as described above. 
Multiple tubes may be used to collect the required amount. 
 
2. Draw 7-10mL of blood into the labeled lavender/purple top tube(s). A minimum 
of 3mL is needed for processing. 
 
3.  Immediately after collection, gently invert the tube 5-10 times to mix the blood 
and EDTA. 
   
4. Whole blood specimens should be refrigerated (4°C) until the specimens can be 
shipped. Ship whole blood to the GOG Tissue Bank the day the specimen is 
collected. If the whole blood absolutely cannot be shipped the day it is 
collected, the tube(s) should be refrigerated (4°C) until the specimen can be 
shipped. 
 
VII. Submitting Form TR 
 
A completed copy of Form TR must accompany each specimen shipped to the GOG 
Tissue Bank (or alternate laboratory). Handwritten forms will not be accepted. 
 
Note: A copy does not need to be sent to the GOG Tissue Bank (or alternate 
laboratory) if specimens are not collected. 
 
Form TR should be printed from the Translational Research Form screen in Rave 
using the “PDF File” link at the top of the form. Clicking this link will generate a 
PDF of Form TR in a “SEDES style” format. Do not use the “Printable Version” or 


 
 
GOG-0283 
 
73 
 
“View PDF” links at the bottom of the form or any other method to print the form, 
as these formats will not be accepted. 
  
Retain a printout of the completed form for your records. 
  
Please contact User Support at the GOG Statistical and Data Center if you need 
assistance (Email: support@gogstats.org; Phone: 716-845-7767). 
 
VIII. Shipping Translational Research Specimens 
 
A completed copy of Form TR must be included for each translational 
research specimen. 
 
A. FFPE Tissue 
 
FFPE tissue and a copy of the corresponding pathology report should be 
shipped using your own container at your own expense to: 
 
GOG Tissue Bank / Protocol GOG-GOG-0283 
Nationwide Children’s Hospital 
700 Children’s Dr, WA1340 
Columbus, OH 43205 
Phone: (614) 722-2865 
FAX: (614) 722-2897 
Email: GOGBank@nationwidechildrens.org 
 
Do not ship FFPE tissue for Saturday delivery. 
 
B. Whole Blood 
 
All whole blood specimens should be shipped to the GOG Tissue Bank (address 
above). 
 
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 


 
 
GOG-0283 
 
74 
 
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, 
place 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). 
 
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. 
  
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 container (e.g., cardboard 
FedEx box). 
 
5. Insert a copy of Form TR for each specimen.  
 
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. 
 
IX. Distributing Specimens for Translational Research 
 
The GOG Statistical and Data Center and Tissue Bank (or alternate laboratory) will 
coordinate the distribution of specimens to approved investigators for translational 
research. 
 
Investigators will not be given access to any personal identifiers. 
 


 
 
GOG-0283 
 
75 
 
Investigators will be responsible for the direct supervision and oversight of 
translational research and for keeping accurate records. 
 
Investigators will ensure the results are linked to the appropriate specimen-specific 
identifiers and are responsible for transferring relevant laboratory data to the GOG 
Statistical and Data Center. 
 
At the discretion of the Chair of the Committee on Experimental Medicine and the 
Director of the GOG Tissue Bank, investigators may be required to ship any 
specimens (or by-products) remaining after the completion of the translational 
research to the GOG Tissue Bank. 
 
A. FFPE 
 
FFPE will be batch shipped on a monthly basis to Dr. Robert Soslow: 
 
ATTN: Carlene Gonzalez 
Memorial Sloan-Kettering Cancer Center 
Department of Pathology 
1275 York Ave 
New York, NY 10065 
Phone: 212-639-7297 
FAX: 929-321-5015 
Email: gonzalc5@mskcc.org 
 
B. Whole Blood 
 
The GOG Tissue Bank will extract DNA from whole blood. DNA will be batch 
shipped on a monthly basis to Dr. David Hyman: 
 
ATTN: Nancy Bouvier 
Center for Molecular Oncology 
Memorial Sloan Kettering Cancer Center 
408 E 69th #Z-320 
New York, NY 10021 
Phone: 646-888-3761 
Email: bouviern@mskcc.org, skicmopm@mskcc.org 
 
Please email prior to shipping specimens. 
 
X. 
Banking Translational Research Specimens for Future Research 
 
Translational research specimens will remain banked in the GOG Tissue Bank and 
made available for approved research projects if the patient has given permission to 
use her specimens for future health research. The patient’s choices will be recorded 
on the signed informed consent document and the online Specimen Consent 


 
 
GOG-0283 
 
76 
 
Application. At the time of specimen selection for project distribution, the most 
recent consent information will be used. 
 
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 revokes permission to use her specimens, the GOG Tissue Bank will 
destroy (or return) any remaining specimens. The patient’s specimens will not be 
used for any further research; however, any specimens distributed for research prior 
to revoking consent cannot be returned or destroyed. In addition, the patient cannot 
be removed from any research that has been done with her specimens prior to 
revoking consent. 
 
Note: If return of specimens is requested, shipping will be at the institution’s 
expense.