Randomized Phase III Clinical Trial of Adjuvant Radiation Versus Chemoradiation in Intermediate Risk, Stage I/IIA Cervical Cancer Treated With Initial Radical Hysterectomy and Pelvic Lymphadenectomy (NCT #01101451)
Phase: PHASE3
Conditions: Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma, Not Otherwise Specified, Stage I Cervical Cancer AJCC v6 and v7, Stage IA Cervical Cancer AJCC v6 and v7, Stage IB Cervical Cancer AJCC v6 and v7, Stage IIA Cervical Cancer AJCC v7
Sponsor: GOG Foundation

i 
 
SUMMARY OF CHANGES 
Protocol Amendment #7 to: GOG-0263 
 
NCI Protocol #: GOG-0263 
Local Protocol #: GOG-0263 
 
NCI Version Date: March 14, 2022 
Protocol Date: March 14, 2022 
 
# 
Section 
Change 
1 
Title 
Page(s) 
NCI Version Date has been updated  
 
2 
11.1 
Administratively edited “post surgical” to hyphenated form “post-surgical” 
3 
11.4 
• Accrual description has been revised, justification added to support 
closing the study.  
• Figure added to reflect current data as of 1/7/2022 
 
4 
11.52 
Revised accrual section to support plans for study closure.  
5 
11.82 
Administratively edited the words “one sided” to hyphenated form “one-sided” 
6 
11.84 
• Added sub-section 11.84 to describe updated analysis plan titled 
“Suspending Follow-up for the Final Analysis (1/2022)” 
• Updated RFS analysis table added.  
 
7 
ICF 
• NCI Version Date updated.  No other changes were made. 

NCI Protocol #: GOG-0263 
Version Date: March 14, 2022 
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PROTOCOL GOG-0263 
RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS CHEMORADIATION 
IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED WITH INITIAL RADICAL 
HYSTERECTOMY AND PELVIC LYMPHADENECTOMY (NCT #01101451) (05/12/2014) 
NCI Version:  March 14, 2022 
Includes Revisions 1-7 
POINTS: 
PER CAPITA – 20 
MEMBERSHIP – 6 
TR PER CAPITA – Award based on specimen submission with 1.0 point for whole blood (05/12/2014). 
Lead Organization: NRG / NRG Oncology (05/12/2014) 
 
 
 
 
 
 
STUDY CHAIR  
 
 
 
 
STUDY CO-CHAIR (05/12/2020) 
SANG YOUNG RYU, MD  
 
 
KEVIN ALBUQUERQUE, M.D., MS, FRCS 
DEPT OB/GYN, KOREA CANCER CTR  
 
HAROLD C. SIMMONS COMP CANCER CTR 
215-4 GONGNEUNG-DONG, NOWAN-GU 
 
RAD/ONC, U.T. SOUTHWESTERN MED CTR 
SEOUL, KOREA, 139-709 
 
 
 
2280 INWOOD ROAD 
TEL:  +82-2-970-1227 
 
 
 
 
DALLAS, TX 753 
FAX:  +82-2-970-1227 
 
 
 
 
TEL: (214) 645-8309 
Email : ryu@kcch.re.kr 
 
 
 
 
FAX :  (214) 645-8527 
 
 
 
 
 
 
 
Email:  kevin.albuquerque@utsouthwestern.edu 
 
NURSE CONTACT (05/12/2020)  
 
 
 
ANNE HEUGEL, RN, OCN, CCRP 
UNIVERSITY HOSPITALS           
 
 
PATHOLOGIST 
CASE WESTERN MED. CENTER 
 
           WILLIAM RODGERS, M.D., Ph.D. 
DEPT GYN/ONC                  
 
 
 
See GOG Website Directory 
11100 EUCLID AVE, MAC 7128 
CLEVELAND, OH 44106  
 
 
 
QUALITY OF LIFE 
TEL: (216) 844-8160 
 
 
 
 
KAREN M. GIL, Ph.D. 
FAX: (216) 844-8596 
 
 
 
 
See GOG Website Directory 
Email:  anne.heugel@UHhospitals.org 
 
 
 
 
 
 
 
 
TRANSLATIONAL RES SCI. (05/12/2014) 
STATISTICIAN  
 
 
 
 
HEATHER A. LANKES, Ph.D., MPH 
WEI DENG, Ph.D. 
 
 
 
See GOG Website Directory 
See GOG Website Directory 
 
 
 
 
 
 
 
 
 
 
 
RTOG CO-CHAIR (05/12/2014) 
TRANSLATIONAL RESEARCH CHAIR  
 
WILLIAM SMALL, M.D. 
MICHAEL BIRRER, M.D., Ph.D.  
 
 
See GOG Website Directory 
See GOG Website Directory 
 
 
 
 
 
OPEN TO PATIENT ENTRY APRIL 12, 2010; REVISED MAY 25, 2010; REVISED JUNE 13, 2011; REVISED MAY 
12, 2014; REVISED MARCH 5, 2018; REVISED APRIL 23, 2018; REVISED MAY 12, 2020; REVISED MARCH 14, 
2022.  
 
This protocol was designed and developed by the Gynecologic Oncology Group (GOG). It is intended to be used only in 
conjunction with institution-specific IRB approval for study entry. No other use or reproduction is authorized by GOG 
nor does GOG assume any responsibility for unauthorized use of this protocol. 
Participating Organizations (05/12/2014) 
 
ALLIANCE / Alliance for Clinical Trials in Oncology 
ECOG-ACRIN / ECOG-ACRIN Cancer Research Group 
SWOG / SWOG 

NCI Protocol #: GOG-0263 
Version Date: March 14, 2022 
- 2 - 
 
PROTOCOL GOG-0263 
RANDOMIZED PHASE III CLINICAL TRIAL OF ADJUVANT RADIATION VERSUS 
CHEMORADIATION IN INTERMEDIATE RISK, STAGE I/IIA CERVICAL CANCER TREATED 
WITH INITIAL RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY  
NCI Version:  March 14, 2022 
CONTACT INFORMATION (05/12/2014)(05/12/2020) 
For regulatory 
requirements: 
For patient enrollments: 
For data submission 
Regulatory 
documentation must be 
submitted to the CTSU 
via the Regulatory 
Submission Portal. 
 (Sign in at 
www.ctsu.org, and select 
the Regulatory > 
Regulatory Submission.)  
 
Institutions with patients 
waiting that are unable 
to use the Portal should 
alert the CTSU 
Regulatory Office 
immediately at 1-866-
651-2878 to receive 
further instruction and 
support. 
 
Contact the CTSU 
Regulatory Help Desk at 
1-866-651-2878 for 
regulatory assistance. 
Refer to the patient 
enrollment section of the 
protocol for instructions on 
using the Oncology Patient 
Enrollment Network 
(OPEN). OPEN is accessed 
at 
https ://www.ctsu.org/OPE
N_SYSTEM/ or 
https://OPEN.ctsu.org. 
 
Contact the CTSU Help 
Desk with any OPEN-
related questions by phone 
or email : 1-888-823-5923 
or ctsucontact@westat.com. 
 
 
Use the SDC Electronic Data Entry System 
(SEDES) online application found at the GOG 
Web Menu page, to view and print a copy of 
each form along with instructions, and to 
submit forms electronically.  All amendments 
to forms submitted through SEDES must also 
be submitted through SEDES.  The original 
form and required copies for forms NOT 
submitted online must be mailed to the GOG 
SDC. 
 
GOG Statistical and Data Center 
Roswell Park Cancer Institute, Carlton and 
Elm Streets, Buffalo, New York, 14263-0001 
716-845-5702 
FAX: 716-845-8393 
 
Do not submit study data or forms to CTSU 
Data Operations. Do not copy the CTSU on 
data submissions. 
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.  
Access to the CTSU members’ website is managed through the Cancer Therapy and Evaluation Program 
– Identity and Access Management (CTEP-IAM) registration system and requires user log in with a 
CTEP-IAM username and password. Permission to view and download this protocol and its supporting 
documents is restricted and is based on person and site roster assignment housed in the CTSU RSS.   
For clinical questions (i.e. patient eligibility or treatment-related) Contact the Study PI of the Lead 
Protocol Organization 
For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data 
submission) Contact the CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
 
OPEN TO PATIENT ENTRY APRIL 12, 2010; REVISED MAY 25, 2010; REVISED JUNE 13, 2011;  
REVISED MAY 12, 2014; REVISED MARCH 5, 2018; REVISED APRIL 23, 2018; REVISED MAY 12, 2020, 
REVISED MARCH 14, 2022.
 
 
 

NCI Protocol #: GOG-0263 
Version Date: March 14, 2022 
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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
** The 6th cycle of cisplatin may be omitted if all radiotherapy has been completed. 
 
Brachytherapy boost is NOT allowed on this protocol 
 
Pathology Requirements to Confirm Eligibility: see sections 4.2, 7.2 and 10.2 for a description of 
the H&E stained pathology slides and reports that are required for this research study. 
 
Quality of Life Research: see Sections 4.5, 4.6, 7.4 and 10.2 for a description of the quality of 
life assessments and time points for data collection for this research study. 
Regimen II (CRT arm) Schedule 
Cycle  
1 
2 
3 
4 
5 
6 
Day 
1 
8 
15 
22 
29 
36 
Cisplatin 
X 
X 
X 
X 
X 
X** 
Radiation 
 
• Post-operative Stage I-IIA cancer of cervix with intermediate risk factors (IRF) 
• Squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma histology 
• 
GOG performance status 0-2 
• Baseline Quality of Life Assessment 
• Smoking History Questionnaire 
RANDOMIZE 
 Stratification factors: IRF, performance status, 
radiation modality, cooperative group 
Regimen I (control arm) 
Radiation Therapy: 
(External pelvic standard radiation or 
IMRT)  
Regimen II (CRT arm) 
Concurrent Cisplatin and Radiation Therapy 
(External pelvic standard radiation or IMRT)  
 
Cisplatin 40mg/m2 (max=70mg) IV over 1-2 
hours weekly x 6 cycles with radiation therapy 
(see Regimen II Schedule below) 

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Translational Research: see sections 7.3 and 10.2 as well as Appendix II for a description of the 
specimen requirements and laboratory testing for this research study. 
 
CT of chest/abdomen/pelvis or PET/CT is required within 30 days of documentation of any site 
of relapse. 
 
 
 
 

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TABLE OF CONTENTS 
PAGE 
 
 
1.0 
OBJECTIVES 
                                                                                                      - 7 - 
1.1 
Primary Objectives 
- 7 - 
1.2 
Secondary Objectives 
- 7 - 
1.3 
Quality Of Life Objectives 
- 7 - 
1.4 
Translational Research Objectives 
- 7 - 
2.0 
BACKGROUND AND RATIONALE 
                                                                  - 8 - 
2.1 
Rationale for Chemo-Radiation 
- 8 - 
2.2 
Rationale of Intensity Modulated Radiation Therapy (IMRT) 
- 12 - 
2.3 
Rationale for Quality of Life Assessment 
- 12 - 
2.4  
Translational Research Component: 
- 13 - 
2.5  
Inclusion of Women and Minorities 
- 16 - 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS                                                           - 17 - 
3.1 
Eligible Patients 
- 17 - 
3.2 
Ineligible Patients 
- 17 - 
4.0 
STUDY MODALITIES 
                                                                                        - 19 - 
4.1 
Surgery 
- 19 - 
4.2 
Pathology Requirements 
- 19 - 
4.3 
Radiation Therapy 
- 19 - 
4.4 
Chemotherapy 
- 31 - 
4.5 
Quality of Life Assessments (QOL) 
- 34 - 
5.0 
TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE (06/13/2011) 
(05/12/2014) 
 
 
 
                                                                - 37 - 
5.1 
Registration Procedures (05/12/2014)(05/12/2020) 
- 37 - 
5.2 
Patient Entry and Registration  (05/12/2014)(05/12/2020) 
- 43 - 
5.3 
Credentialing Requirements (05/12/2014)(05/12/2020) 
- 43 - 
5.4 
Treatment Plan 
- 46 - 
6.0 
TREATMENT MODIFICATIONS                                                                             - 47 - 
6.1  
Treatment Modification of Radiation Therapy 
- 47 - 
6.2  
Treatment Modification of Concurrent Chemotherapy 
- 49 - 
7.0 
STUDY PARAMETERS 
                                                                                        - 51 - 
7.1 
Observations and Tests (06/13/2011) (05/12/2014) 
- 51 - 
7.2 
STAINED PATHOLOGY SLIDE REQUIREMENTS FOR CENTRAL REVIEW TO 
CONFIRM ELIGIBILITY 
- 52 - 
7.3 
TRANSLATIONAL RESEARCH 
- 53 - 
7.4 
Quality of Life Research 
  - 53 - 
8.0 
EVALUATION CRITERIA                                                                                         - 56 - 
8.1 
Outcome Measures 
    - 56 - 
9.0 
DURATION OF STUDY 
                                                                                        - 57 - 
9.1 
Each patient should complete the study treatment unless disease recurrence occurs or 
toxicity prohibits further therapy. 
- 57 - 
9.2 
Each patient should be followed quarterly for two years and every six months for three 
additional years, and thereafter annually or at the time of recurrence until death. 
- 57 - 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES                                     - 58 - 
10.1 
ADVERSE EVENT REPORTING FOR ALL REGIMENS (COMMERCIAL AGENTS 
AND RADIATION THERAPY ADMINISTRATION) (05/12/2014) 
- 58 - 

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10.2  
GOG DATA MANAGEMENT FORMS 
- 61 - 
11.0   STATISTICAL CONSIDERATIONS 
                                                                - 64 - 
11.1 
Study Design and Registration 
- 64 - 
11.2 
Study Objectives 
- 64 - 
11.3 
Data Elements and Endpoints 
- 65 - 
11.4 
Accrual 
- 65 - 
11.5 
Hypothesis, Planning Parameters and Sample Size 
- 66 - 
11.6 
Analyses and Evaluation of Study Endpoints 
- 69 - 
11.7 
Study Monitoring, Data Quality Control and Semi-annual Reports (05/12/2014) 
- 72 - 
11.8 
Interim Analyses 
- 73 - 
11.9 
Planned Minority Inclusion 
- 75 - 
APPENDIX I 
                                                                                                    - 82 - 
APPENDIX II (05/12/2014)                                                                                                     - 83 - 
APPENDIX III (05/12/2014)                                                                                                     - 88 - 
APPENDIX IV (05/12/2014)(05/12/2020)                                                                                 - 90 - 
 
 
 
 

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1.0 
OBJECTIVES  
 
1.1 
Primary Objectives 
 
1.11 
To determine if post-operative adjuvant chemo-radiation therapy (CRT) 
can significantly improve recurrence-free survival (RFS) when compared 
to radiation therapy (RT) alone in Stage I-IIA cervical cancer patients with 
intermediate risk factors after treatment with radical hysterectomy. 
 
1.2 
Secondary Objectives 
 
1.21 
To determine whether post-operative adjuvant CRT can improve overall 
survival (OS) when compared to RT alone in Stage I-IIA cervical cancer 
patients with intermediate risk factors after treatment with radical 
hysterectomy. 
1.22 
To assess differences (across treatment arms) in incidence and severity of 
therapy attributed adverse events utilizing the active version of CTCAE. 
1.23 
To provide assessment of patient risk vs. benefit (positive study only). 
 
1.3 
Quality Of Life Objectives 
 
1.31 
To determine whether post-operative adjuvant CRT improves the health 
related Quality of Life (QOL) (compared to RT alone) as measured by 
FACT-Cx TOI and produce favorable toxicity profiles (with particular 
focus on treatment related genitourinary, gastrointestinal, neurological, 
pain and sexual adverse events). 
 
 
1.4 
Translational Research Objectives  
 
1.41 
To bank archival tumor tissue for research including studies that evaluate 
the association between biomarkers and RFS, OS, and clinical-surgical-
pathologic characteristics in patients randomized to post-operative 
adjuvant CRT compared to RT alone. 
 
1.42 
To bank DNA from whole blood for research including studies that 
evaluate associations between single nucleotide polymorphisms (SNPs) 
and measures of clinical outcome including RFS, OS, and adverse events 
in patients randomized to post-operative adjuvant CRT compared to RT 
alone. 
 
 
 
 
 

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2.0 
BACKGROUND AND RATIONALE 
 
2.1 
Rationale for Chemo-Radiation 
 
 
Early cervical cancer has a relatively favorable prognosis with more than an 80% 
survival rate.1 However, there are still high mortality rates and poor prognoses in 
cases of recurrent disease. Several clinico-pathologic risk factors for recurrence 
have been identified and investigated the clinical significance in cervical cancers. 
2-5 
 
 
High risk factors, such as lymph node metastasis, parametrial invasion and 
positive resection margins increase the recurrence rate up to 40% after surgery in 
early cervical cancer  patients.5-8 In this high-risk group, concurrent 
chemotherapy with RT reduces recurrences and improves survival. In an earlier 
study, Peter et al. showed that adjuvant CRT in post-operative cervical cancer 
with high risk factors increased progression free survival from 63% to 80%, and 
the overall survival rate from 71% to 81%.6   Several randomized clinical trials 
also consistently showed that the addition of concurrent chemotherapy to RT 
reduces the relative risk of death from cervical cancer by approximately 50% by 
decreasing local failure and distant metastasis. Based on these clinical trials, 
weekly intravenous cisplatin at 40mg/m2 in combination with concurrent RT was 
established as a new standard treatment for the locally advanced cervical 
cancers.6, 9-13  
 
 
However, the role of intermediate factors, such as deep stromal invasion, large 
tumor size, and lympho-vascular space involvement still remains controversial.14-
16   Worrying about over-treatment, many physicians are reluctant to treat the 
patients who have  intermediate risk factors with CRT. This reluctance is 
understandable, given that patients with intermediate risk factors have a favorable 
prognosis: five-year survival without any adjuvant treatment for 85-90% of this 
population.1   However, those who have two or more intermediate risk factors 
showed approximately a 30% recurrence rate, which is similar to that of patients 
with one high-risk factor; thus implying the need for adjuvant treatment. A 
Gynecologic Oncology Group (GOG) study confirmed that such intermediate risk 
factors existed in 25% of all Stage IB cervical cancers and that these factors 
increase the risk of recurrence from 2% to 31% at 3 years.14-20  
 
Currently, the standard regimen for the patients with two or more intermediate-
risk factors is adjuvant RT, which is based on GOG-0092.17, 18  In GOG-0092, 277 
cervical cancer patients with two or more intermediate risk factors after radical 
hysterectomy were randomized to either a “no further treatment” (NFT) group or 
a  RT group. Even though the improvement of overall survival with RT did not 
reach statistical significance at two years, the RT arm showed a statistically 
significant reduction in risk of recurrence (HR=0.54, p=0.007) and an increase of 
two-year recurrence-free interval from 79 to 88% at the cost of low toxicity.17   
The recently published outcomes of GOG-0092 have shown that the use of 

NCI Protocol #: GOG-0263 
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adjuvant RT was associated with a hazard ratio of 0.54 for recurrence (p=.007), 
hazard ratio of 0.58 for progression or death (p=0.009), and hazard ratio of 0.70 
for overall survival (p=0.74). There was a greater decrease of recurrence among 
patients with adenocarcinomas and adenosquamous carcinomas than among those 
with squamous carcinomas. Women randomized to the RT arm did experience an 
increased rate of Grades 3 and 4 toxicity compared to those who did not undergo 
RT.18  
Recently, we retrospectively investigated whether weekly cisplatin-based 
concurrent CRT increases three-year recurrence-free intervals in cervical cancer 
patients with two or more intermediate risk factors.21  Of  the 735 patients with 
post-operative cervical cancers  included in this retrospective study, 172 were 
identified as having had intermediate risk factors.  These 172 patients were then 
categorized into the following groups: no further treatment group (NFT, n=34), 
RT group (RT, n=49), and concurrent CRT group (CRT, n=89). The three-year 
recurrence-free interval increased to 90.5% (RT) from 72.5% (NFT), and further 
increased to 98.7% (CRT), making the disease almost curable by adding weekly 
cisplatin at 40mg/m2.  
 
Based on these results and previous clinical trials that have consistently shown the 
benefit of concurrent chemotherapy, we suggest that the addition of concurrent 
chemotherapy to RT may increase recurrence-free survival in cervical cancer 
patients with intermediate risk factors. 
 
This study is to investigate whether there is any improvement of three-year 
recurrence- free interval in post-operative cervical cancer patients with 
intermediate risk factors through the  addition of weekly cisplatin chemotherapy 
to RT. We expect at least a 6% increase (from 87 to 93%) of three-year 
recurrence-free interval in patients receiving concurrent chemotherapy compared 
to the RT alone group.  
 
Our study will provide more sophisticated treatment for patients with cervical 
cancer with intermediate risk factors, who comprise 20-25% of all post-operative 
cervical cancers. 
 
 

NCI Protocol #: GOG-0263 
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Table 1. GOG-0092 showed that the recurrence rate reduced from 27.9% to 
15.3% by adjuvant RT in patients with cervical cancer with intermediate risk 
factors. 
Recurrences by Treatment Regimen 
 Site of Recurrence 
 
 
 
            RT  
 
                   No further therapy 
  
 
 
 
 
        (N=137) 
 
 
         (N=140) 
No Evidence of Disease 
 
 
     116(84.7%) 
 
                           101(72.1%) 
Recurrences 
 
 
 
       21(15.3%)                                    
            39(27.9%) 
Local 
 
 
 
 
       18(13.1%)                                    
            27(19.3%) 
   Vagina 
 
 
 
 
         2   
 
 
                                8 
   Pelvis 
 
 
 
                         15                                                
            17 
   Vagina and pelvis 
 
 
 
         1 
 
 
                                2 
Distal 
 
 
 
                           3(2.2%) 
 
 
           10(7.1%) 
   Abdomen                                                                                  0 
 
 
                               3 
   Abdomen and pelvis                                                                 0                                                                          1 
   Lung                                                                           
         2                                                                          2 
   Lung and pelvis                                                           
         0                                                                          2 
   Lung and brain 
 
                                             0                                                   
             1 
   Bone and supraclavicular lymph node                                     1                                                                          1 
Unknown                                                                  
         0(0%)                                                                  2(1.4%) 
GOG-0092 showed that those who have two or more intermediate risk factors had 
a 27% recurrence rate without any treatment, which was reduced to 15% by 
adjuvant RT (Table 1). Interestingly, not only local recurrences, but also distant 
recurrences were reduced by RT, for reasons that are not yet clearly understood.  
The two-year disease-free interval was 79% in the NFT group and 88% in the RT 
group, which provides the basis for the 88% recurrence-free interval in the control 
arm (RT arm) of our protocol (Figure 1).  
Most “pattern of failure” analyses in previous GOG trials have been limited to 
initial sites of failure.  For example, if a local recurrence is documented, it is 
recorded as the site of failure, and further documentation of other sites of potential 
relapse is no longer required.  Accurate and complete pattern of failure analysis is 
important to clearly delineate ALL sites of relapse, and will be important in 
helping to determine future strategies in addressing these sites of risk.  Current 
widely available ‘total body’ tomographic imaging techniques (CT of the 
chest/abdomen/pelvis, or PET/CT) should be used, at the time of first documented 
recurrence in any given location, to fully assess for other sites of disease relapse.  
 
 

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Figure 1. GOG-0092 showed that adjuvant RT increased 2-year disease free 
survival in patients with cervical cancer with intermediate risk factors. 
 
 
 
 
 
 
 
 
 
 
 
 
Our retrospective study showed that concurrent CRT increased three-year 
recurrence-free interval 8% more than the adjuvant RT, which supports the 
favorable role of CRT in cervical cancers with intermediate risk factors.21  In this 
retrospective study, three-year recurrence-free interval increased to 90.5% by 
adjuvant RT (RT arm, n=49) from 72.5% of control (NFT arm, n=34), and further 
increased to 98.7% (CRT arm, n=89), thus making the disease highly curable with 
the addition of weekly cisplatin at 40m/m2 to pelvic RT. (Figure 2). 
 
Figure 2. A retrospective study showed that concurrent CRT increased three-year 
recurrence-free interval from 72% (NFT), 90% (RT) to 98% (CRT) in patients 
with cervical cancer with two or more intermediate risk factors. 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2.2 
Rationale of Intensity Modulated Radiation Therapy (IMRT) 
 
In an attempt to potentially decrease both acute and late radiation-related 
toxicities, Intensity Modulated Radiation Therapy (IMRT) has been increasingly 
used by many practitioners in the post-hysterectomy setting. IMRT will be 
allowed at the discretion of the treating radiation oncologist, subject to 
appropriate physician and facility credentialing. In 2002, Mell et al. performed a 
nationwide survey and found that 15% of the IMRT users in the United States had 
treated at least one gynecologic patient with IMRT.22 In the follow-up survey 
done in 2004, this percentage had increased to 35%, making gynecology the 
fourth most common site treated with IMRT and the most rapidly growing IMRT 
site overall in the United States.23 RTOG recently completed a phase II trial 
evaluating the transportability of IMRT to multiple institutions in the post-
operative setting in patients with both cervical and endometrial cancer. The results 
for the endometrial arm were recently presented at ASTRO in Boston and found 
IMRT was feasible across multiple institutions in the post-operative setting.24 
 
2.3 
Rationale for Quality of Life Assessment   
 
The results of GOG-0092 demonstrated a significant decrease in the recurrence 
rate with an increase in Grade 3/4 adverse events in women treated with adjuvant 
pelvic radiotherapy following radical hysterectomy versus women who received 
no further treatment.17 Nine (7.0%) of the 128 women who received radiotherapy 
had 11 episodes of Grade 3 or 4 adverse events compared with three (2.1%) in the 
group receiving no further  
treatment.  The addition of cisplatin in this protocol 
is anticipated to further increase three-year recurrence-free interval to 93%, 
although at the cost of increased toxicity.   
 
Cisplatin neurotoxicity primarily affects sensory nerves; sensory neuropathy first 
appears about one month after initiation of therapy and can follow from total 
exposure as low as 200 mg/m2. 25 Symptoms of neuropathy may start after 
cessation of therapy and can persist over the following months. 25, 26   
Neurotoxicity scores of patients receiving cisplatin in GOG-0179 were not 
increased above pre-treatment levels prior to cycles 2 and 5; however, 
neurotoxicity scores were significantly higher 9 months post-random assignment 
than they were pre-5th cycle of chemotherapy.27  It is not known to what extent the 
addition of cisplatin in this setting will result in symptoms that affect QOL. Given 
the estimated difference in rate of recurrence (87% versus 93%), the potential 
effect of cisplatin on neurotoxicity and QOL will be an important component of 
treatment decisions. 
 
An additional factor that may affect the decision to include cisplatin is the effect 
of acute cisplatin toxicities on completion of all 6 cycles of therapy. Cisplatin 
chemotherapy is associated with nausea, vomiting, and diarrhea.28-30 RT may also 

NCI Protocol #: GOG-0263 
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be associated with nausea, vomiting, abdominal cramping and diarrhea.28 
However, cisplatin-induced toxicities added to RT toxicities may result in 
treatment delays and/or fewer women completing the 6 cycles of therapy.  QOL 
assessments will provide information on the extent to which the addition of 
cisplatin affects treatment completion. 
 
 
2.4  
Translational Research Component:  
 
2.41 
Background and rationale for banking archival tumor for research 
 
The GOG has a number of studies in cervical cancer that indicate the 
importance of markers of angiogenesis and hypoxia in this disease site. 
GOG-9911 evaluated whether markers of tumor angiogenesis were 
associated with progression-free survival (PFS) and overall survival (OS) 
in women with high-risk, early-stage cervical cancer treated on the multi-
center randomized Phase III trial (SWOG 8797/GOG-0109/RTOG 91-12). 
One hundred seventy-three tumor specimens were analyzed by semi-
quantitative immunohistochemical (IHC) staining for vascular-endothelial 
growth factor (VEGF, pro-angiogenesis factor), thrombospondin-1 (TSP-
1, anti-angiogenesis factor), CD31 (non-specific endothelial marker), and 
CD105 (tumor-specific endothelial marker). Tumoral histoscores (HS) 
were calculated for VEGF using the formula: [% cells positive x (intensity 
+1)]. TSP-1 specimens were categorized as negative or positive. CD31 
and CD105 microvessel density (MVD) “hotspots” were counted in three 
20X high-power fields. Associations between angiogenesis markers and 
survival were evaluated.  TSP-1 expression was observed in 65% of cases 
while 66% expressed high VEGF (≥ 200), 34% exhibited high CD31 
(CD31 ≥ 110) and 66% displayed high CD105 (CD105 ≥ 28). In 
univariate analyses, CD31 MVD, but not tumor TSP-1, was associated 
with improved PFS (HR=0.37; 95% CI=0.18-0.76; p=0.007) and OS 
(HR=0.37; 95% CI=0.17-0.79; p=0.010). After adjusting for prognostic 
clinical covariates, high CD31 MVD, but not TSP-1,VEGF or CD105 
MVD, was an independent prognostic factor for PFS (HR=0.36; 95% 
CI=0.17-0.75; p=0.006) and OS (HR=0.36; 95% CI=0.17-0.79; p=0.010). 
In conclusion, tumor angiogenesis measured by CD31 MVD is an 
independent prognostic factor for both PFS and OS in high-risk, early-
stage cervical cancer.  We hypothesize this finding may be explained by 
improved treatment response in well-vascularized, well-oxygenated 
tumors.  These results were recently accepted for publication in 
Gynecologic Oncology in 2009. 
 
GOG-9911 was then used to determine whether carbonic anhydrase-IX 
(CA-IX), a marker of hypoxia, was associated with progression-free 
survival (PFS) and overall survival (OS) in this cohort of women with 
high-risk, early-stage cervical cancer treated with adjuvant pelvic 
radiotherapy with or without  radio-sensitizing chemotherapy on a multi-

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center randomized Phase III trial (SWOG 8797/GOG-0109/RTOG 91-12). 
CA-IX expression was detected using an immunohistochemistry assay and 
categorized as low when ≤ 80% of tumor cells exhibited CA-IX staining 
and high when >80% tumor cells display CA-IX staining. Associations 
between CA-IX expression and clinical characteristics, angiogenesis 
marker expression and clinical outcome were evaluated.  High CA-IX 
expression was observed in 35/166 (21.1%) of cases.  CA-IX expression 
was not associated with age, race, stage, cell type, grade, positive margins, 
parametrial extensions, positive lymph nodes or lymphovascular space 
invasion but was correlated with tumor size categorized as <2 cm, 2-2.9 
cm, or ≥3 cm (r=0.233, p=0.001) and cervical invasion confined to the 
inner two-thirds compared with the outer third of the cervix (r=0.176, 
p=0.003). CA-IX expression was not associated with 
immunohistochemical expression of p53, CD-31, CD-105, 
thrombospondin-1 or vascular endothelial growth factor. Women with 
high versus low CA-IX expression had slightly worse PFS (p=0.053) and 
significantly worse OS (p=0.044). After adjusting for prognostic clinical 
covariates, high CA-IX expression was an independent prognostic factor 
for PFS (hazard ratio [HR]=1.996; 95% confidence interval [CI]=1.072-
3.715; p=0.029) and OS (HR=2.575; 95% CI=1.314-5.049; p=0.006). In 
conclusion, tumor hypoxia as measured by immunohistochemical 
expression of CA-IX appears to be an independent prognostic factor for 
both PFS and OS in high-risk, early-stage cervical cancer.    
 
 
In follow up to these findings, an analysis was then performed to explore 
the relationship between CD31-MVD and CA-IX as part of the GOG-9911 
protocol. Although categorized CD31-MVD and CA-IX are not 
themselves correlated, these biomarkers appear to have an independent 
inverse association with prognosis in the cervical cancer patients treated 
with adjuvant pelvic radiotherapy with or without radio-sensitizing 
chemotherapy. Women who have tumors with high CD31-MVD (high 
angiogenesis) and low CA-IX (low hypoxia) had the best PFS and OS, 
those with low CD31-MVD (low angiogenesis) and low CA-IX (low 
hypoxia) had intermediate PFS and OS, and those with low CD31-MVD 
(low angiogenesis) and high CA-IX (high hypoxia) had the worst PFS and 
OS.  This finding supports our hypothesis that improved treatment 
response is observed in the well-vascularized and well-oxygenated tumors 
with high CD31-MVD and low CA-IX expression. These results were 
presented at a Plenary Presentation at the 2009 Society of Gynecologic 
Oncologists (SGO) meeting in San Antonio, TX.31 
 
Translational research objectives were prospectively embedded in a series 
of randomized Phase III treatment protocols in women with cervical 
cancer, including GOG-0191, GOG-0219 and GOG-0240. The GOG 
programmatically incorporated the same objective into each of these trials 
to determine definitely which markers of angiogenesis and hypoxia are 

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associated with PFS, OS and clinicopathologic characteristics. The 
immunohistochemistry assays for CD31-MVD, CD105-MVD, VEGF, 
TSP-1 and CA-IX in the GOG-191 cohort are currently underway.  GOG-
219 is still accruing patients and specimens, and GOG-240 was opened to 
patient accrual in April 2009.   
 
The GOG proposes to bank archival tumor specimens (block or 5 to 15 
unstained slides depending on the quantity of available material) from 
cervical cancer patients participating in this phase III treatment protocols 
to expand the resource of well-annotated tumor specimens linked with 
detailed clinical, surgicopathologic, treatment and outcome data from 
patients enrolled at multiple institutions in North America and Korea.  
This resource will enable the research community to not only study 
cervical cancer biology, progression and factors that either positively or 
negatively impact treatment response and therapeutic efficacy but 
moreover to identify and validate biomarkers with predictive, prognostic 
and/or therapeutic value in this disease site.  This will be an optional but 
high priority effort for GOG Institutions outside the United States. 
 
2.42 
Background and rationale for banking DNA from whole blood for 
research   
 
The National Cancer Institute is encouraging cooperative clinical trial 
groups, including the Gynecologic Oncology Group, to bank whole blood 
from women participating in Phase III clinical trials such that the blood 
specimens will be linked to clinical outcome data (recurrence-free 
survival, progression-free survival, overall survival, response, and adverse 
effects) and information regarding treatment. The purpose of this effort is 
to support research, including pharmacogenomic and pharmacogenetic 
research. Specifically, it is well known that individual single nucleotide 
polymorphisms (SNPs) and SNP profiles are associated with many clinical 
aspects of cancer.  This includes risk of developing invasive cancer, risk of 
recurrence of cancer, patient survival, and adverse events.  We propose to 
bank DNA from whole blood to enable researchers to use genome-wide 
SNP and individual SNP analyses to identify SNPs that correlate with a 
variety of clinical measures, including but not limited to patient survival, 
recurrence of disease, response, and adverse events. 
 
Women who are candidates for this clinical trial will be asked to give 
permission for 10 ml of their blood to be collected for research.  No matter 
what the women decide to do, it will not affect their care. The women can 
still participate in this GOG study even if they do not allow their blood to 
be collected and used for research. For financial, practical and logical 
reasons this will be an optional, but high priority effort for women 
enrolled at GOG institutions within the United States. 
 

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2.5  
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 stage I-IIA cervical 
cancer population treated by participating institutions. 
 
 

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3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS  
 
3.1 
Eligible Patients  
 
 3.11 Pathologically proven primary cervical cancer I-IIA with squamous cell 
carcinoma, adenosquamous carcinoma or adenocarcinoma initially treated 
with a standard radical hysterectomy with pelvic lymphadenectomy. 
 
3.12  Patients with the following characteristics (depth of stromal invasion and 
lymphovascular space involvement to be pathologically confirmed): 
 
3.121 Positive capillary-lymphovascular space involvement and one of 
the following: 
• Deep third penetration 
• Middle third penetration, clinical tumor ≥ 2 cm 
• Superficial third penetration, clinical tumor ≥ 5 cm 
 
3.122 Negative capillary-lymphatic space involvement: 
• Middle or deep third penetration, clinical tumor ≥ 4 
 
3.13 
Patients must have adequate: 
 
3.131  Hematologic function: ANC ≥ 1,500/mcl, platelets ≥ 100,000/mcl 
 
3.132 Renal function: creatinine ≤ ULN or calculated creatinine 
clearance ≥ 60 Ml/min 
 
3.133 Hepatic function:  bilirubin ≤ 1.5 x normal, alkaline phosphate and 
SGOT ≤ 3 x normal 
 
3.14 
GOG performance status 0, 1, 2. 
 
3.15 
Patients should not be randomized less than 3 weeks post-surgery but will 
not be acceptable for randomization more than 8 weeks post-surgery. 
 
3.16 
Patients who have met the pre-entry requirements specified in Section 7.0. 
 
3.17 
Patients must have signed an approved informed consent and authorization  
 
permitting release of personal health information. 
 
 
3.18 
Patients must be ≥ 18 years of age. (06/13/2011) 
 
3.2 
Ineligible Patients  
 
3.21 
Patients with tumor in the parametria, pelvic lymph nodes or any other 
extra uterine site or with positive surgical margins. 

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3.22 
Patients with septicemia or severe infection. 
 
 
3.23 
Patients with intestinal obstruction or gastrointestinal bleeding. 
 
 
3.24 
Patients with postoperative fistula. 
 
3.25 
Patients with cervix cancer who have received any previous radiation or 
chemotherapy. 
 
3.26 
Patients whose circumstances do not permit completion of the study or the  
 
required follow-up. 
 
3.27 
Patients with renal abnormalities requiring modification of radiation field  
 
(pelvic kidney, renal transplant, etc). 
 
3.28 
Patients with GOG Performance Status of 3 or 4. 
 
3.29 
Patients with a history of other invasive malignancies, with the exception 
of non-melanoma skin cancer, are excluded if there is any evidence of 
other malignancy being present within the last five years.  Patients are also 
excluded if their previous cancer treatment contraindicates this protocol 
therapy. 
 
 

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4.0 
STUDY MODALITIES   
 
4.1 
Surgery 
 
All patients will have had a radical hysterectomy and pelvic lymphadenectomy 
trans-abdominally or laparoscopically. Para-aortic lymphadenectomy is not 
required.  
 
4.2 
Pathology Requirements 
 
4.21 
Eligible Patients: Patients must have a histologic diagnosis of primary 
invasive cervical cancer Stage I-IIA (squamous cell carcinoma, 
adenosquamous carcinoma or adenocarcinoma) with histologically-
documented depth of cervical stromal invasion and/or capillary-lymphatic 
space involvement. 
 
4.22 
Ineligible Patients: Patients with a gynecologic malignancy other than 
invasive cervical cancer Stage I-IIA or lacking histologically-documented 
depth of cervical stromal invasion or capillary-lymphatic space 
involvement 
 
4.23 
Requirements and Instructions: H&E stained pathology slides are required 
for central review by the GOG Pathology Committee to confirm eligibility 
and to confirm depth of cervical invasion and capillary-lymphatic space 
involvement for the protocol.  See Sections 7.2 and 10.2 for specific 
requirements and instructions for the stained pathology slides, pathology 
reports, and forms. 
 
4.3 
Radiation Therapy 
 
**Brachytherapy boost is not allowed in this protocol.  IMRT is allowed in 
this protocol ** 
 
4.31 
NOTE: Patients will receive external beam radiotherapy using 4-field 
‘standard’ radiotherapy or Intensity Modulated Radiation Therapy (IMRT) 
techniques.   Megavoltage equipment with ≥ 6 MV photons and a 
minimum of 100 cm SAD is required.  Before ANY patient is enrolled on 
this study, the treating radiation oncologist must complete online a 
Knowledge Assessment Questionnaire found on the IROC Houston 
(formerly the Radiological Physics Center [RPC]) website 
(http://irochouston.mdanderson.org).  
 
Prior to use of IMRT on study, credentialing through IROC Houston, 
including an IMRT phantom study, must be completed (see Section 5.2).  
The treatment plan for the first patient to be treated at that institution on 
this protocol must be digitally submitted via TRIAD ;it will be processed 

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in preparation for rapid review. A rapid review will be performed PRIOR 
TO DELIVERING ANY PROTOCOL TREATMENT. The rapid review 
will be conducted by IROC Houston in collaboration with a radiation 
oncologist and suggestions regarding protocol compliance will be 
forwarded to the participating institution’s radiation oncologist.  The 
treatment plans for subsequent patients enrolled at a site will not be 
required to be reviewed prior to treatment, but documentation will still 
need to be submitted for post-therapy central review. Once data has been 
submitted to TRIAD, complete a DDSI contact information form at 
http://www.rtog.org/CoreLab/TRIAD.aspx.  (05/12/2014) 
 
For IMRT details, see Section 4.33.   
 
 
 
All patients should be sufficiently healed from surgery before beginning 
RT; they are to begin no sooner than 3 weeks and no later than 8 weeks 
post-operatively.   
 
4.311 Radiation Therapy Quality Control and Documentation:  
 
 
All participating institutions are required to be monitored by IROC 
Houston through the remote auditing program. IROC Houston is 
funded by the NCI to support clinical trials employing RT and will 
supervise the dosimetry quality control for this clinical trial. 
(05/12/2014) 
 
4.32 
Standard Radiation Therapy: 
 
4.321  Dose specifications: 
 
 
4.3211 External beam pelvic radiotherapy will be given to a dose 
of 50.4 Gy in 28 fractions (1.8 Gy/fraction). (If using 
IMRT, please see Section 4.33 for dose specification and 
requirements.). Treatment will be delivered once daily, 5 
fractions per week, over 5.5 weeks.  All prescribed fields 
treated daily.  
 
4.3212 For standard radiotherapy, the specification of the target 
dose is in terms of a dose to a point at or near the center of 
the target volume. For all field arrangements the dose 
specification point is the common isocenter of all beams. 
 
4.322  Technical factors 
RT will be delivered by means of mega-voltage equipment 
with ≥ 6 MV photons, and a minimum of 100 cm SAD. 
 

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4.323  Standard Radiotherapy Localization and Simulation: (see 
Section 4.33 below for IMRT specifications) 
 
For standard radiotherapy, all fields require simulation on a 
dedicated simulator and portal verification on the RT unit. 
CT-based treatment planning is required.  For standard RT, 
CT scan slice thickness of up to 5 mm is permitted.  The 
intended target volume includes the upper half of the 
vagina, the parvaginal and parametrial tissues, and the first 
echelon nodal chains (obturator, internal iliacs, and external 
iliacs).  Customized blocking of the femoral heads, bowel, 
and iliac crests should be carefully performed to avoid 
under-coverage of the obturator foramen, parametria, and 
iliac nodal chains.  
 
4.3231 AP-PA pelvic field set-up: 
  
 
Superior - To include at least L5-S1 interspace, but 
not more cephalad than the superior aspect of the 
L5 vertebral body. 
 
 
Inferior - At least down to the mid obturator 
foramen (a temporary vaginal marker, such as a 
tampon or OB-Gyn applicator/swab, should be 
placed at the time of simulation to mark the vaginal 
apex, and assure that at least the upper 3 cm of the 
non-distended vagina is included). 
 
 
Lateral - At least 1cm beyond the lateral margins of 
the bony pelvis at the widest plane through the 
pelvis 
 
4.3232 Lateral pelvic field set-up: 
 
 
Superior and inferior borders: same as above  
 
 
Anterior border: transverse line through anterior  
portion of the pubic symphysis  
 
Posterior border: to include at least the S3-S4 
interspace, with adequate margin (3 cm) on the 
temporary vaginal marker and sufficient coverage 
of the parametria and uterosacral ligaments 
 
4.324  Documentation requirements for standard radiotherapy: 
 

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All fields treated require simulation and beam verification 
films.  For standard 4-field radiation treatments, simulation 
or digital reconstructed radiographs (DRR) of each of the 
treatment fields, are to be obtained and submitted for 
evaluation.  For non-IMRT plans, contouring of the vagina, 
parametria and nodal volumes are optional.  However, if 
CTVs are defined for standard 4-field radiation treatment 
planning, 3-D reconstruction of these volumes should also 
be submitted for review. 
 
For patients treated with standard 4-field radiotherapy, full 
dosimetry plans, including multi-plane and multi-view 
isodose distributions will be obtained and submitted. 
 
4.325  Compliance Criteria for Standard Radiation Therapy 
 
4.3251 Per protocol:  See section 4.3211 
 
4.3252 Variation acceptable: 
- Interruption of external beam RT of less than 7 
consecutive days. 
- The minimum dose to the dose specification point 
is greater or equal to 48.6 Gy 
- Maximum dose to a volume of at least 0.03 cc of 
tissue within the convergence of the treatment fields 
should not exceed 107% of the prescription dose 
 
4.3253 Deviation Unacceptable 
- Field of RT is other than what is outlined in the 
protocol. 
- Interruption of external beam RT of more than 7 
consecutive days 
- The minimum delivered dose to the dose 
specification point is less than 48.6 Gy. 
-Maximum dose to a volume of at least 0.03 cc of 
tissue within the convergence of the treatment fields 
exceed 107% of the prescription dose. 
 
4.33 
IMRT  
Credentialing by IROC Houston is required for IMRT treatments (see 
Section 5.2). Please refer to the RTOG Gynecological Atlas for volume 
specifications.  The Atlas may be accessed on the RTOG website:  
http://www.rtog.org/atlases/gynatlas/main.html. (05/12/2014) 
 
 

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4.331 Dose Specifications 
 
Prescription dose will be according to the following specifications:  
 
4.3311 The vaginal/parametrial planning target volume (PTV) 
(ITV – see section 4.3344 - with 7.0 mm margin) and nodal 
PTV will receive 50.4 Gy in 28 fractions.  Treatment will 
be delivered once daily, 5 fractions per week, over 5.5 
weeks.  All targets will be treated simultaneously.  Breaks 
in treatment should be minimized. 
  
4.3312 The dose is prescribed to cover 97% of the 
vaginal/parametrial PTV and the nodal PTV.  A volume of 
at least 0.03 cc within any PTV should not receive > 110% 
of the prescribed dose.  No volume within the PTV that is 
0.03 cc or larger can receive a dose that is < 93% of its 
prescribed dose.  Any contiguous volume of 0.03 cc or 
larger of the tissue outside the PTV’s must not receive > 
110% of the dose prescribed to the composite PTV.     
 
4.332   Technical Factors 
 
4.3321 Megavoltage equipment capable of delivering static 
intensity modulation with a multi-leaf collimator or 
dynamic intensity modulation (using a multi-leaf collimator 
or tomotherapy) is required. The use of three-dimensional 
conformal radiotherapy (3D-CRT) using forward-planned 
IMRT treatment planning methods is acceptable.  The use 
of compensators or partial transmission blocks is also 
acceptable as long as dose specifications and constraints are 
satisfied.  
 
4.3322 Recognizing that higher energies with higher monitor units  
 
increase neutron contamination, a 6-10 MV energy photon 
beam is recommended.  
 
 
4.333 Localization, Simulation, and Immobilization 
 
4.3331 Prior to simulation, it is recommended that a temporary 
non-distending vaginal marker be inserted into the vaginal 
apex to help identify the vaginal apex on the CT scan.  
Radiopaque markers that distend or otherwise alter the 
vaginal anatomy should not be used.  
 
4.3332 Patients will be immobilized in the supine position in an 
immobilization device. Patients should, at least, be 
immobilized in a device that fixes the position of the trunk 

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and proximal legs.  Patients will be treated daily in the 
immobilization device.  
 
 
4.3333 Treatment planning CT scans will be required to define 
tumor and clinical and planning target volumes.  The 
maximal thickness of the CT scan slices should be no more 
than 3 mm for IMRT planning.  The treatment planning CT 
scan should be acquired with the patient in the same 
position and immobilization device as for treatment 
 
4.334 Treatment Planning/Target Volumes 
 
4.3341 Two separate treatment planning CT scans (full bladder and  
empty bladder CT scans, as described below) are required 
and then should be fused together prior to outlining target 
volumes. The patient will be instructed to drink 32 ounces 
of fluid 30-60 minutes before simulation. A CT scan 
simulation will be performed with the full bladder, and a 
second CT will be performed after the patient has voided 
for the empty bladder scan.  
 
4.3342 In this study, which is used for post-operative patients with 
no gross disease, there should not be a gross tumor volume 
GTV.  
 
4.3343 The Clinical Target Volume (CTV) is defined as areas 
considered to contain potential microscopic disease, 
delineated by the treating physician.  The overall CTV 
includes both the vaginal/parametrial ITV and the nodal 
CTV.  
 
4.3344 Internal Target Volume (ITV) is defined as the combined 
volume of the vagina and parametria that is in both the 
empty and full bladder CT scans that are done at the time of 
simulation and fused together.  This volume accounts for 
internal organ motion.  
 
4.3345 The Planning Target Volume (PTV) will provide a margin 
around the CTV/ITV to compensate for the variability of 
treatment setup.  Careful consideration should be made 
when defining the superior and inferior margins in three 
dimensions.  
 
4.3346 Planning of the IMRT will be done on the full bladder scan 
with full heterogeneity correction enabled in the treatment 
planning system.  

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4.3347 The treatment plan used for each patient will be based on 
an analysis of the volumetric dose, including dose volume 
histogram (DVH) analyses of the PTV (CTV/ITV with a 7 
mm margin) and critical normal structures. The treatment 
aim will be the delivery of RT to the PTVs and the 
exclusion of non-involved tissues. 
 
 

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4.335 Planning Priorities: 
 
Dose to nodal PTV and vaginal/parametrial ITV/PTV are the most 
important planning priorities, followed by the dose to critical 
structures prescription goals.  
 
The priorities in addressing the protocol aims and constraints are in 
Critical Structures (See Section 4.336).  
 
4.3351 The nodal CTV should include lymph nodes that drain the 
involved site and adjacent perinodal soft tissue.  This 
should include the internal (hypogastric and obturator), 
external, and common iliac lymph nodes; presacral lymph 
nodes and soft tissues should be included as well, down to 
the level of S3, to fully include the attachments of the 
uterosacral ligaments. Identification of the CTV usually 
begins with the identification of the iliac vessels. The nodal 
CTV will include the vessel, residual nodal or perinodal 
tissue (on the pelvic wall side, the margin will exclude 
psoas and piriformis muscle) and pertinent clips.  The 
average margin will be 7 mm around the blood vessels, any 
perivascular clips, or any residual radiologically identified 
nodal tissue.  Bone and intraperitoneal small bowel should 
be excluded from the CTV; also, iliopsoas muscle that lies 
adjacent to clinically negative lymph nodes should also be 
excluded from the CTV.  Approximately 1-2 cm of tissue 
anterior to the S1, S2 and S3 sacral segments is usually 
added to the CTV for patients with cervical carcinoma in 
order to include the pre-sacral lymph nodes and uterosacral 
ligament attachments.  The most antero-lateral external 
iliac lymph nodes that lie just proximal to the inguinal 
canal should be excluded from the CTV (i.e., nodal CTV 
should stop right at the level of the femoral head).  The 
CTV of the nodes should end 7mm below the level of the 
sacral promontory (or no higher than the bifurcation of the 
common iliac vessels), and the PTV for nodes will stop at 
the axial level of the sacral promontory. (See GYN atlas for 
examples:  http://www.rtog.org/gynatlas/main.html.)  
4.3352 The vaginal and parametrial CTV should actually be an 
ITV, which will account for an internal organ motion.  It is 
recommended that a temporary non-distending vaginal 
marker be inserted into the vaginal apex to help identify the 
vaginal apex on the CT scan.  Radiopaque markers that 
distend or otherwise alter the vaginal anatomy should not 

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be used.  The ITV is drawn after the full and empty bladder 
scans are fused together, and it should encompass the 
vagina and parvaginal/parametrial soft tissues from both 
scans.  This is because patients are not able to maintain 
constant levels of bladder filling, despite careful 
counseling.  Patients should, however, be treated with a full 
bladder, because full bladder pushes the small bowel up 
and out of the field. If gas/stool distends the rectum on the 
treatment planning CT, the ITV should be expanded to 
include the anterior half of the rectal circumference, to 
account for evacuation/variation of the rectal contents 
during the treatment course.  The inferior limit should 
include at least 3 cm of the upper vaginal cuff, or at least 
down to the level of the mid-obturator foramen.  The lateral 
margin of the vaginal/parametrial ITV should be to the 
obturator muscle. (06/13/2011) 
 
4.3353 PTV Definition: 
Nodal PTV will provide a 7-mm margin (anteriorly, 
posteriorly, laterally, as well as in the superior and inferior 
directions) around the nodal CTV.  The vaginal/parametrial 
PTV will provide a 7 mm margin (anteriorly, superiorly, 
inferiorly, laterally and posteriorly) around  the 
vaginal/parametrial CTV/ ITV.   The overall PTV will 
consist of the combined nodal and vaginal/parametrial 
PTVs 
 
4.3354 The definition of volumes will be in accordance with the 
1993 ICRU Report #50: Prescribing Recording and  
Reporting Photon Beam Therapy and 1999 ICRU Report 
#62: Prescribing, Recording and Reporting Photon Beam 
Therapy (Supplement to ICRU Report 50).  
 
4.336 Critical Structures 
 
4.3361 Normal structures will be contoured using the full-bladder 
CT scan. 
 
4.33611 
Bladder – will be outlined on every slice, 
including the portion inferior to the planning 
target volume. The contour includes the 
bladder contents. 
 
4.33612 
Rectum – will be outlined on every slice, 
including the portion inferior to the planning 
target volume and superior to the level that it 

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leaves the posterior pelvis, including the 
rectosigmoid. The rectum and rectosigmoid 
will be outlined to 2 cm superior to the PTV, 
and no more.  The contour includes the 
rectum contents. 
 
4.33613 
Small bowel – will be outlined on every 
slice, including up to 2 cm above the PTV 
and no more. It includes the volume 
surrounding loops of small bowel out to the 
edge of the peritoneum because the bowel 
may lie within this space at any time 
throughout the course of treatment. Care 
must be taken to delineate the small bowel 
as precisely as possible (i.e., large bowel 
loops such as transverse colon, cecum, and 
rectosigmoid should NOT be included in the 
small bowel volume). 
 
4.3362 The dose constraints for critical structures are as follows 
(06/13/2011): 
 
 
 
- Bowel:  ≤ 30% to receive > 40 Gy 
 
- Rectum:  ≤ 80% to receive > 40 Gy, Dmax < 55 Gy 
 
- Bladder:  ≤ 35% to receive > 45 Gy 
 
4.3363 IV contrast may be used during simulation to help better 
define the vessels; however, it is not required.  Rectal 
contrast is not recommended because it may interfere with 
the planning process and may possibly cause anatomical 
distortion.  
 
4.3364 All tissues to be irradiated must be included in the CT scan. 
CT scan thickness should be 0.3 cm or smaller through the 
region that contains the primary target volumes and at least 
4 cm above and below the target volumes. The superior 
limit of scanning will be at least at the L2-L3 interspace 
and inferior limit will be below the perineum.  
 
4.3365 The ITV and CTV and normal tissues must be outlined on 
all CT slices in which the structures exist on the full-
bladder scan.  ITV contours will be modified to include the 
excursion of target tissues as demonstrated on the empty 
bladder scan (ITV), and should be further modified if there 
is significant gas/stool distention of the rectum on the 
treatment planning CT (see Section 4.3352). Using the full 

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bladder scan, all normal tissues will be outlined on all CT 
slices in which the CTV and ITV exist and up to 2 cm 
superior the PTV. (See Section 4.334 for more detailed 
definitions.) (06/13/2011) 
 
4.3366 Lymph node groups at risk including the following:  
• Internal iliac (obturator and hypogastric) nodes  
• External iliac nodes down to the level of the top of the    
 
femoral heads  
• The presacral nodes down to the level of S3  
• The obturator nodes – inferiorly to upper 1/3 of the     
 
obturator fossa 
4.337 Documentation Requirements: 
Verification orthogonal films or images are required.  For all forms 
of IMRT dose delivery, orthogonal films or images that localize 
the isocenter placement shall be obtained.  The length of the 
treatment field shall be indicated on these films.  These films will 
not be collected but should be held by the institution and available 
for review if requested. 
 
4.3371 For IMRT plans, all plans must be submitted electronically 
via TRIAD for review, in addition to what is required from 
IROC Houston in Section 10.2.   (05/12/2014) 
 
4.3372 For IMRT plans, Dose-Volume Histograms (DVHs) are to 
be obtained for each one of the target volumes defined 
above, as well as the critical surrounding structures, and 
need to be submitted for evaluation.  
 
For submission to TRIAD, the structure names MUST be 
match exactly as listed below or resubmission may be 
required 
 
Structure Name 
Description 
ITV 
Envelope of Vagina and Parametria in bull and empty bladder scans. 
Required 
CTVn 
Nodal CTV 
Required 
 
CTV_5040 
ITV combined with Nodal CTV 
Required 
PTVp_5040 
ITV with a 7.0 mm margin 
Required 
PTVn_5040 
Nodal CTV with a 7 mm margin 

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Required 
PTV_5040 
Nodal PTV combined with vaginal/parametrial PTV 
Required 
Bladder 
Bladder 
Required 
Rectum 
Rectum 
Required 
BowelSpace 
Bowel 
Required 
NonPTV 
External minus PTVs 
Required 
External 
External Skin 
Required 
(05/12/2014) 
  
 
4.338 Compliance Criteria for IMRT 
 
 
Per protocol:  Interruption of 0 days 
 
Variation acceptable:  Interruption of 1-7 consecutive days 
 
Deviation unacceptable:  Interruption of ≥ 8 consecutive days 
 
4.3381 Target volumes (PTV) 
Composite PTV to 50.4 Gy 
- Per protocol:  The prescription criteria in Section 4.331 
are fulfilled. 
- Variation acceptable:  The 0.03 cc volume of overdose for 
the PTV exceeds 110% of the prescribed dose but remains 
at or below 115%.  No volume within this PTV that is 0.03 
cc or larger receives a dose that is < 91% of its prescribed 
dose. 
- Deviation Unacceptable:  A total of 0.03 cc of the PTV 
receives a dose that is over 115% of the prescribed dose.  A 
volume within this PTV that is 0.03 cc or larger receives a 
dose that is < 91% of its prescribed dose. 
 
4.3382 Critical normal structures 
 
 
Bowel: 
 
 
Per protocol:  ≤ 30% receives > 40 Gy.  No volume within 
bowel that is 0.03 cc or larger receives a dose that is > 
110% of the prescription dose. 
 

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Variation acceptable: > 30% receives > 40 Gy, but ≤ 45 Gy.  
A volume of at least 0.03 cc of bowel exceeds 110% of the 
prescribed dose, but remains at or below 115% 
 
Deviation unacceptable:  > 30% receives > 45 Gy.  A 
volume of at least 0.03 cc of bowel exceeds 115% of the 
prescribed dose. 
 
Rectum (06/13/2011): 
 
Per protocol:  ≤ 80% receives > 40 Gy.  No volume within 
rectum that is 0.03 cc or larger receives a dose that is > 
110% of the prescription dose. 
 
Variation acceptable: > 80% receives > 40 Gy, but ≤ 50 Gy.  
A volume of at least 0.03 cc of rectum exceeds 110% of the 
prescribed dose, but remains at or below 115% 
 
Deviation unacceptable:  > 80% receives > 50 Gy.  A 
volume of at least 0.03 cc of rectum exceeds 115% of the 
prescribed dose. 
 
Bladder: 
 
Per protocol:  ≤ 35% receives > 45 Gy.  No volume within 
bladder that is 0.03 cc or larger receives a dose that is > 
110% of the prescription dose. 
 
Variation acceptable: > 35% receives > 45 Gy, but ≤ 50 Gy.  
A volume of at least 0.03 cc of bladder exceeds 110% of 
the prescribed dose, but remains at or below 115% 
 
Deviation unacceptable:  > 35% receives > 50 Gy.  A 
volume of at least 0.03 cc of bladder exceeds 115% of the 
prescribed dose. 
 
4.4 
Chemotherapy 
 
4.41  Formulation: Cisplatin (Cis-diamminedichloroplatinum) 
 
Cisplatin is available in aqueous solution in 50 mg and 100 mg vials with 
9 mg/Ml of sodium chloride. 
 
4.42 
Preparation: Aluminum reacts with cisplatin causing precipitation 
formation and loss of potency, therefore, needles, or intravenous sets 
containing aluminum parts that may come in contact with the drug must 
not be used for the preparation or administration of cisplatin. 

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4.43  Storage: The aqueous solution should be stored at room temperature and 
protected from light. 
 
4.44  Adverse effects (please see package insert for more information): 
 
4.441 Frequent: Leukopenia, thrombocytopenia, anemia, nausea, 
vomiting, nephrotoxicity, ototoxicity, peripheral neuropathy, 
electrolyte imbalance, hypocalcemia, hypomagnesemia, 
aminoglycoside ototoxicity, ocular toxicity, and allergic reactions. 
 
4.442 Infrequent: Cardiac abnormalities, anorexia, elevated SGOT, rash,  
alopecia, and acute myeloid leukemia. 
 
4.443  NOTE: Aminoglycoside antibiotics given before, with, or after 
Cisplatin may potentiate renal toxicity and should be avoided 
whenever possible. 
 
4.444  Severe renal toxicity can be largely avoided by induction of a 
diuresis before, during, and after treatment. 
 
4.445 Mild renal dysfunction is a common complication (10%) of 
chronic  
therapy and may require discontinuation of therapy if creatinine > 
1.5 x Institutional upper limit normal (ULN) develop. 
 
4.446 Mild or severe electrolyte abnormalities may occur (5%) as acute 
or chronic complications, especially hypokalemia or 
hypomagnesemia. 
 
Monitoring of electrolytes and electrolyte replacement will usually 
correct these abnormalities. Rarely, severe hypomagnesemia and 
hypocalcemia may require replacement therapy and 
discontinuation of treatment with cisplatin. 
 
4.447 Allergic reactions are rare. If accompanied by respiratory 
symptoms, allergic reactions require discontinuation of treatment. 
Patch or skin tests are recommended for patients with suspected 
allergy to cisplatin. An emergency set for the treatment of allergic 
reactions should be available in the treatment area. 
 
4.448  Local necrosis and thrombophlebitis can be avoided by careful  
administration. 
 
4.449 Neurotoxicity may be related to cumulative dose and severe 
toxicity can be largely avoided by careful monitoring for evidence 

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of paresthesias and timely discontinuation of treatment. Ataxia has 
been described. 
 
4.4410 Ototoxicity may occur.  
 
NOTE: Eighth (VIII) nerve toxicity resulting in hearing loss and 
(less commonly) vestibular symptoms is a well-documented 
complication of cisplatin treatment and is usually related to total 
cumulative dose. It is advised that patients placed on cisplatin, 
whether as a single agent therapy or combination, be questioned 
concerning hearing loss. Patients with a history of hearing loss 
should be considered for pre-treatment audiometry with follow-up 
audiometry as clinically indicated. It is recommended that patients 
be queried concerning hearing loss before each course of cisplatin. 
 
4.45 
Drug Interactions 
Phenytoin: cisplatin decreases the effect of phenytoin 
Aminoglycosides, amphotericin B: increased renal toxicity 
Loop Diuretics (furosemide): increased risk of ototoxicity 
 
4.46 
Supplier: Commercially available. 
 
4.47 
Concurrent Cisplatin Administration (06/13/2011) 
1,000 ml of normal saline should be infused intravenously one hour before 
cisplatin. Increased oral intake of water should be encouraged starting the 
day before treatment. Additional fluid may be given as needed for 
symptomatic support. 
 
Patients enrolled will receive 40 mg/ m2 of cisplatin (maximum total dose 
of 70 mg/week). Drug may be diluted in 250 ml 0.9% sodium chloride and 
administered over one or two hours. Alternatively, cisplatin may be 
diluted and administered per established institutional guidelines. 
 
Details of pre- and post-hydration are left to the discretion of the treating 
physician, but at least 1,000 ml 0.9% sodium chloride prior to cisplatin 
and another 500-1,000 ml 0.9% sodium chloride after cisplatin are 
recommended. 
 
This is the minimum fluid administration recommendation and more 
fluid may be given at the discretion of the treating physician. 
 
Cisplatin will be given on the first day of external RT (Day 1), preferably 
approximately four hours prior to RT, cisplatin will be repeated as above 
on days 8, 15, 22, 29, and 36 (preferably Mondays) of external RT. 
 
See Appendix V for General Chemotherapy Guidelines 

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The 6th cycle of cisplatin may be omitted if all radiotherapy has been 
completed. 
 
4.5 
Quality of Life Assessments (QOL) 
 
4.51 
The Functional Assessment of Cancer Therapy – (FACT-G, Version 4) is 
a brief, validated, sensitive 27-item measure for evaluating QOL in 
patients receiving treatment for cancer32. In addition to a total QOL score, 
subscale scores for physical, functional, social and emotional well being 
are produced.  Utilization of this questionnaire will allow for a 
determination of the extent to which the addition of chemotherapy affects 
overall QOL as well as domain specific QOL (for example, functional 
well being).   
 
4.52 
The four sensory items from the FACT-Neurotoxicity (Ntx) subscale will 
be included to assess potential side effects from cisplatin chemotherapy 
(FACT-Ntx 1 through FACT-Ntx 4).  A recent study examined the use of 
this subscale in patients with advanced endometrial cancer treated with 
doxorubicin/cisplatin doxorubicin/cisplatin/paclitaxel prior to 1-7 cycles 
of treatment.33 The sensory items (Ntx1 though Ntx4) accounted for 80% 
of treatment differences and 63% of longitudinal changes in the subscale 
score.  These four questions will therefore be included so that assessment 
of neurotoxicity is included, but response burden is minimized.   
 
4.53 
Response to a single question from the Brief Pain Inventory (BPI) will be  
included in order to obtain important information on pain levels, shown to 
be significant in other cervical cancer studies,27 without significantly 
increasing response burden (Describe pain at its worst during the last 24 
hours).34   
 
4.54 
In order to understand effects of the proposed treatments, the following 
patient-reported outcomes will also be measured: 
 
4.541  The cervix subscale of the FACT-Cx, which consists of 15 
questions developed from interviews with patients and clinicians 
involved with cervical cancer,35 has been used to assess QOL in 
women with cervical cancer who are undergoing cisplatin 
chemotherapy.27,35 
 
4.542 Acute toxicities associated with RT include nausea, vomiting, 
abdominal cramping and diarrhea.28 Grade 3-4 adverse events in 
women receiving RT reported in GOG-0092 17 were hematologic, 
gastrointestinal, and genitourinary.  The FACT-Cx includes 
questions that directly address nausea, lack of appetite, side effects 
of treatment, pain, and control of urine.   
 

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4.543 Five additional questions that address control of bowels, cramping 
and diarrhea will be included.  These questions are expected to 
more sensitively measure less severe grades of acute toxicity.  The 
five additional questions are: 
 
BL2.  I urinate more frequently than usual. 
C3.  I have control of my bowels. 
O3.  I have cramps in my stomach area. 
C4.  I can digest my food well. 
C5.  I have diarrhea. 
 
4.544 All questions will be combined into one Scantron form. Total 
number of questions will be 52:  FACT-Cx (42), Neurotoxicity 
questions (4), additional toxicity questions (5), brief pain question 
(1). 
 
4.55  Translation of the instruments into Korean. 
 
The FACT-G, the Cervix subscale, the five additional questions, and the 
Neurotoxicity subscale have been translated into Korean and validated by 
the Center on Outcomes, Research and Education (CORE), Evanston 
Northwestern Healthcare, Evanston, IL.  This translation involved a 
rigorous methodology, psychometric testing and cognitive interviewing to 
ensure that the resulting measure was both conceptually equivalent as well 
as cross-culturally valid utilizing the linguistic experience of the 
translation team and staff experienced with the outcome measures.  Details 
of the methodology used for translation have been published.36-38   
 
Yun et al 39 have published a validation study of the Korean version of the 
Brief Pain Inventory (BPI) that included a back translation.  Korean 
versions of QOL instruments were used to further validate the translated 
BPI in 132 patients with recurrent or metastatic cancer.   
 
4.6 
Timing of Quality of Life Assessments: 
 
Baseline:  Longitudinal QOL scores are correlated 27 so that assessment of 
longitudinal QOL scores in this study will include a baseline measurement 
completed prior to randomization to control for effects influencing patients prior 
to treatment.  The baseline QOL assessment will be completed prior to 
entry/randomization.   
 
During treatment: To assess the effect of adding cisplatin chemotherapy to RT, 
QOL assessments will be made 3 weeks following the first day of treatment and 7 
weeks following the first day of treatment. In women receiving cisplatin 
chemotherapy, the QOL assessment 3 weeks following the first day of treatment 
should be done prior to starting a cisplatin cycle. 

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Long term effects: QOL data will be collected at 9 months following the first day 
of treatment. This will allow for determination of the acute effects of cisplatin as 
well as effects that may appear following cessation of treatment.25, 28 This will 
also allow for assessment of potentially additive toxicities due to surgery and RT 
with cisplatin therapy. 
 
All QOL questionnaires are to be administered by the nurse/data manager or the 
physician. Patients should be told that they will be asked to complete the same 
questionnaire again at specific time intervals that coincide with 
appointments/treatment.  If patients need assistance, they may be helped.  Please 
record the reason for assistance.  Patients should be instructed to answer all 
questions and report any symptoms even if they are not related to cancer or 
treatment.  Family members should be asked to wait in another room while the 
patient completes the questionnaire. 
 
Women Who Terminate Treatment or Experience Treatment Delays:  
 
QOL assessments are not tied to treatment so should be given at the specified 
time (3 weeks following the first day of treatment, 7 weeks following the first day 
of treatment, 9 months following the first day of treatment), even if women 
experience treatment delay or termination. 
 
 
 

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5.0 
TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE (06/13/2011) 
(05/12/2014)   
 
5.1 
Investigator and Research Associate Registration with CTEP (05/12/2014) 
(05/12/2020) 
Food and Drug Administration (FDA) regulations and National Cancer Institute 
(NCI) policy require all individuals contributing to NCI-sponsored trials to register 
and renew their registration annually. To register, all individuals must obtain a 
Cancer Therapy Evaluation Program (CTEP) Identity and Access Management 
(IAM) account at https://ctepcore.nci.nih.gov/iam. In addition, persons with a 
registration type of Investigator (IVR), Non-Physician Investigator (NPIVR), or 
Associate Plus (AP) must complete their annual registration using CTEP’s web-
based Registration and Credential Repository (RCR) at 
https://ctepcore.nci.nih.gov/rcr.    
RCR utilizes five person registration types. 
• IVR — MD, DO, or international equivalent; 
• NPIVR — advanced practice providers (e.g., NP or PA) or graduate level 
researchers (e.g., PhD); 
• AP — clinical site staff (e.g., RN or CRA) with data entry access to CTSU 
applications such as the Roster Update Management System [RUMS], 
OPEN, Rave, acting as a primary site contact, or with consenting 
privileges; 
• Associate (A) — other clinical site staff involved in the conduct of NCI-
sponsored trials; and 
• Associate Basic (AB) — individuals (e.g., pharmaceutical company 
employees) with limited access to NCI-supported systems. 
RCR requires the following registration documents: 
 
Documentation Required 
IVR NPIVR AP 
A 
AB 
FDA Form 1572 
✔ 
✔ 
 
 
 
Financial Disclosure Form 
✔ 
✔ 
✔ 
 
 
NCI Biosketch (education, training, employment, license, 
and certification) 
✔ 
✔ 
✔ 
GCP training 
✔ 
✔ 
✔ 
Agent Shipment Form (if applicable) 
✔ 
CV (optional) 
✔ 
✔ 
✔ 
 
An active CTEP-IAM user account and appropriate RCR registration is required to access all 
CTEP and Cancer Trials Support Unit (CTSU) websites and applications. In addition, IVRs and 

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NPIVRs must list all clinical practice sites and Institutional Review Boards (IRBs) covering their 
practice sites on the FDA Form 1572 in RCR to allow the following: 
• Addition to a site roster; 
• Assign the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN; 
• Act as the site-protocol Principal Investigator (PI) on the IRB approval; and 
• Assign the Clinical Investigator (CI) role on the Delegation of Tasks Log (DTL).  
 
In addition, all investigators acting as the Site-Protocol PI (investigator listed on the IRB 
approval), consenting/treating/drug shipment investigator in OPEN, or as the CI on the DTL 
must be rostered at the enrolling site with a participating organization.  
Additional information is located on the CTEP website at 
https://ctep.cancer.gov/investigatorResources/default.htm. For questions, please contact the RCR 
Help Desk by email at RCRHelpDesk@nih.gov. 
 
 
 
5.11 
Cancer Trials Support Unit Registration Procedures 
Permission to view and download this protocol and its supporting 
documents is restricted and is based on person and site roster assignment 
housed in the CTSU Regulatory Support System (RSS). 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU). 
 
5.111 IRB Approval:   
For CTEP and Division of Cancer Prevention (DCP) studies open 
to the National Clinical Trials Network (NCTN) and NCI 
Community Oncology Research Program (NCORP) Research 
Bases after March 1, 2019, all U.S.-based sites must be members of 
the NCI Central Institutional Review Board (NCI CIRB). In 
addition, U.S.-based sites must accept the NCI CIRB review to 
activate new studies at the site after March 1, 2019. Local IRB 
review will continue to be accepted for studies that are not 
reviewed by the CIRB, or if the study was previously open at the 
site under the local IRB. International sites should continue to 
submit Research Ethics Board (REB) approval to the CTSU 
Regulatory Office following country-specific regulations.  
Sites participating with the NCI CIRB must submit the Study 
Specific Worksheet for Local Context (SSW) to the CIRB using 
IRBManager to indicate their intent to open the study locally. The 
NCI CIRB’s approval of the SSW is automatically communicated 
to the CTSU Regulatory Office, but sites are required to contact the 
CTSU Regulatory Office at CTSURegPref@ctsu.coccg.org to 
establish site preferences for applying NCI CIRB approvals across 
their Signatory Network. Site preferences can be set at the network 
or protocol level. Questions about establishing site preferences can 

NCI Protocol #: GOG-0263 
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be addressed to the CTSU Regulatory Office by email or calling 1-
888-651-CTSU (2878). 
Sites using their local IRB or REB, must submit their approval to 
the CTSU Regulatory Office using the Regulatory Submission 
Portal located in the Regulatory section of the CTSU website. 
Acceptable documentation of local IRB/REB approval includes: 
• Local IRB documentation; 
• IRB-signed CTSU IRB Certification Form; and/or 
• Protocol of Human Subjects Assurance Identification/IRB 
Certification/Declaration of Exemption Form. 
In addition, the Site-Protocol Principal Investigator (PI) (i.e. the 
investigator on the IRB/REB approval) must meet the following 
criteria in order for the processing of the IRB/REB approval record 
to be completed: 
• Holds an active CTEP status; 
• Rostered at the site on the IRB/REB approval (applies to US 
and Canadian sites only) and on at least one participating 
roster; 
• If using NCI CIRB, rostered on the NCI CIRB Signatory 
record; 
• Includes the IRB number of the IRB providing approval in 
the Form FDA 1572 in the RCR profile; and 
• Holds the appropriate CTEP registration type for the 
protocol.  
 
Additional Requirements 
Additional requirements to obtain an approved site registration 
status include: 
• An active Federal Wide Assurance (FWA) number; 
• An active roster affiliation with the Lead Protocol 
Organization (LPO) or a Participating Organization (PO); 
and 
• Compliance with all protocol-specific requirements (PSRs). 
Protocol-Specific Requirements for GOG-0263 Site 
Registration 

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This is a study with a radiation and/or imaging (RTI) component 
and the enrolling site must be aligned to an RTI provider. To 
manage provider associations or to add or remove associated 
providers, access the Provider Association page from the 
Regulatory section on the CTSU members’ website at 
https://www.ctsu.org/RSS/RTFProviderAssociation. Sites must be 
linked to at least one Imaging and Radiation Oncology Core 
(IROC) provider to participate on trials with an RTI component. 
Enrolling sites are responsible for ensuring that the appropriate 
agreements and IRB approvals are in place with their RTI 
provider. An individual with a primary role on any roster is 
required to update provider associations, though all individuals at a 
site may view provider associations. To find who holds primary 
roles at your site, view the Person Roster Browser under the 
RUMS section on the CTSU website. 
 
IROC Credentialing Status Inquiry (CSI) Form – this form is 
submitted to IROC Houston to verify credentialing status or to 
begin a new modality credentialing process.  
 
Upon site registration approval in RSS, the enrolling site may 
access OPEN to complete enrollments. The enrolling site will 
select their credentialed provider treating the subject in the OPEN 
credentialing screen and may need to answer additional questions 
related to treatment in the eligibility checklist.   
 
 
5.122 Downloading Site Registration Documents:   
Download the site registration forms from the protocol-specific 
page located on the CTSU members’ website. Permission to view 
and download this protocol and its supporting documents is 
restricted based on person and site roster assignment. To 
participate, the institution and its associated investigators and staff 
must be associated with the LPO or a Protocol Organization (PO) 
on the protocol. One way to search for a protocol is listed below.  
• Log in to the CTSU members’ website 
(https://www.ctsu.org) using your CTEP-IAM username 
and password; 
• Click on Protocols in the upper left of the screen 
o Enter the protocol number in the search field at the 
top of the protocol tree; or 

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o Click on the By Lead Organization folder to 
expand, then select NRG Oncology and protocol 
number GOG-0263 
• Click on Documents, select Site Registration, and download 
and complete the forms provided. (Note: For sites under the 
CIRB, IRB data will load automatically to the CTSU.)  
 
5.123 Requirements For GOG-0263 Site Registration: 
 
 
This is a study with a radiation and/or imaging (RTI) component 
and the enrolling site must be aligned to an RTI provider. To 
manage provider associations or to add or remove associated 
providers, access the Provider Association page from the 
Regulatory section on the CTSU members’ website at 
https://www.ctsu.org/RSS/RTFProviderAssociation. Sites must be 
linked to at least one Imaging and Radiation Oncology Core 
(IROC) provider to participate on trials with an RTI component. 
Enrolling sites are responsible for ensuring that the appropriate 
agreements and IRB approvals are in place with their RTI 
provider. An individual with a primary role on any roster is 
required to update provider associations, though all individuals at a 
site may view provider associations. To find who holds primary 
roles at your site, view the Person Roster Browser under the 
RUMS section on the CTSU website. 
 
 
IROC Credentialing Status Inquiry (CSI) Form – this form is 
submitted to IROC Houston to verify credentialing status or to 
begin a new modality credentialing process.  
 
 
 
5.124 Submitting Regulatory Documents:  
Submit required forms and documents to the CTSU Regulatory 
Office using the Regulatory Submission Portal on the CTSU 
website.  
To access the Regulatory Submission Portal log in to the CTSU 
members’ website, go to the Regulatory section and select 
Regulatory Submission. 
Institutions with patients waiting that are unable to use the 
Regulatory Submission Portal should alert the CTSU Regulatory 
Office immediately at 1-866-651-2878 in order to receive further 
instruction and support. 
 

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5.125 Checking Your Site’s Registration Status: 
 
Site registration status may be verified on the CTSU members’ 
website.  
• Click on Regulatory at the top of the screen; 
• Click on Site Registration; and 
• Enter the sites 5-character CTEP Institution Code and click 
on Go. 
o Additional filters are available to sort by Protocol, 
Registration Status, Protocol Status, and/or IRB 
Type. 
 
Note: The status shown only reflects institutional compliance with 
site registration requirements as outlined within the protocol. It 
does not reflect compliance with protocol requirements for 
individuals participating on the protocol or the enrolling 
investigator’s status with NCI or their affiliated networks. 
 
 

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5.2 
Patient Enrollment (05/12/2014)(05/12/2020)  
The Oncology Patient Enrollment Network (OPEN) is a web-based registration 
system available on a 24/7 basis. OPEN is integrated with CTSU regulatory and 
roster data and with the LPOs registration/randomization systems or the Theradex 
Interactive Web Response System (IWRS) for retrieval of patient 
registration/randomization assignment. OPEN will populate the patient enrollment 
data in NCI’s clinical data management system, Medidata Rave. 
Requirements for OPEN access:   
 
• A valid CTEP-IAM account; 
• To perform enrollments or request slot reservations: Must be on an 
LPO roster, ETCTN corresponding roster, or participating 
organization roster with the role of Registrar. Registrars must hold a 
minimum of an Associate Plus (AP) registration type; 
• Have an approved site registration for the protocol prior to patient 
enrollment. 
 
To assign an Investigator (IVR) or Non-Physician Investigator (NPIVR) as the 
treating, crediting, consenting, drug shipment (IVR only), or receiving 
investigator for a patient transfer in OPEN, the IVR or NPIVR must list the IRB 
number used on the site’s IRB approval on their Form FDA 1572 in RCR. If a 
DTL is required for the study, the IVR or NPIVR must be assigned the 
appropriate OPEN-related tasks on the DTL. 
 
Prior to accessing OPEN, site staff should verify the following: 
• Patient has met all eligibility criteria within the protocol stated 
timeframes; and  
• All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable). 
 
Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information. You may print this confirmation for your 
records.  
 
Access OPEN at https://open.ctsu.org or from the OPEN link on the CTSU 
members’ website. Further instructional information is in the OPEN section of the 
CTSU website at https://www.ctsu.org or https://open.ctsu.org. For any additional 
questions, contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com. 
 
 
 
5.3 
Credentialing Requirements (05/12/2014)(05/12/2020) 
 
5.31 
Credentialing for this protocol will be handled by IROC Houston 

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(formerly the Radiological Physics Center [RPC[).  All information 
regarding credentialing can be found on the IROC Houston website 
(http://irochouston.mdanderson.org ) by selecting “Credentialing”, then 
“GOG.” 
 
5.32 
Before ANY patient is enrolled on this study, the treating radiation 
oncologist must complete on-line a Knowledge Assessment Questionnaire 
found on the IROC Houston website. 
 
Each institution must complete the Facility Questionnaire available on the 
IROC Houston web site by selecting “Protocol GOG-0263”.   
 
5.33 
IMRT credentialing requirements when IMRT is planned: 
 
Institutions must be credentialed for IMRT by IROC Houston for this 
protocol prior to enrolling patients into this study when IMRT is planned.  
Each institution must successfully irradiate a standardized phantom 
available from IROC Houston. Instructions for requesting and irradiating 
the phantom are available at the IROC Houston web site.    Institutions 
that have been previously credentialed for IMRT by RTOG or GOG via 
the head and neck phantom or the pelvic phantom can determine what 
additional requirements must be completed by filling out the 
“Credentialing Status Inquiry” form on the IROC Houston website.  IROC 
Houston will issue credentials for this protocol to the institution and notify 
the GOG Statistical and Data Center. 
 
 
Each Institution must complete the IMRT portion of the Facility 
Questionnaire available on the IROC Houston web site by selecting 
“Protocol GOG-0263”.  Each institution must submit the completed IMRT 
Facility Questionnaire online.  
 
Institution and/or peer-reviewed documentation of target position 
reproducibility [planning treatment volume (PTV) and clinical target 
volume (CTV)] must be consistent with Section 4.334. 
 
5.34 
Digital Radiation Therapy Data Submission Using Transfer of Images and 
Data (05/12/2014)(05/12/2020) 
 
Transfer of Images and Data (TRIAD) is the American College of 
Radiology’s (ACR) image exchange application. TRIAD provides 
sites participating in clinical trials a secure method to transmit 
images. TRIAD anonymizes and validates the images as they are 
transferred. 
TRIAD Access Requirements: 
• A valid CTEP-IAM account.  
• Registration and Credential Repository (RCR) registration 
type of: Associate (A), Associate Plus (AP), Non-Physician 

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Investigator (NPIVR), or Investigator (IVR) registration 
type. Refer to the CTEP Registration Procedures section for 
instructions on how to request a CTEP-IAM account and 
complete registration in RCR. 
• TRIAD Site User role on an NCTN or ETCTN roster. 
 
All individuals on the Imaging and Radiation Oncology Core 
provider roster have access to TRIAD and may submit images for 
credentialing purposes, or for enrollments to which the provider is 
linked in OPEN. 
 
TRIAD Installation: 
To submit images, the individual holding the TRIAD Site User 
role will need to install the TRIAD application on their 
workstation. TRIAD installation documentation is available at 
https://triadinstall.acr.org/triadclient/. 
This process can be done in parallel to obtaining your CTEP-IAM 
account and RCR registration. 
For questions, contact TRIAD Technical Support staff via email 
TRIAD-Support@acr.org or 1-703-390-9858. 
 
 
.. 
 
 

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5.4 
Treatment Plan  
 
Patients who meet the eligibility requirements according to Section 3.0 will be 
assigned randomly to one of the two regimens: 
 
 
 
Arm I: Control Arm; RT alone (Section 4.3) 
 
Arm II: CRT Arm; weekly Cisplatin 40mg/m2 concurrent to RT (Section 4.4)  
 
 

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6.0 
TREATMENT MODIFICATIONS   
 
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.htm).  All 
appropriate treatment areas should have access to a copy of the CTEP Active Version of 
CTCAE. 
 
6.1  
Treatment Modification of Radiation Therapy 
 
Treatment may be interrupted for up to a maximum 2 weeks for CTCAE Grade 3 
or 4 gastrointestinal or hematologic toxicities, but every effort should be made to 
minimize treatment delays.  In particular, those with Grade 3 toxicities who 
remain outpatients should receive maximal supportive care, including medications 
and IV fluid/electrolytes supplementation that would reduce or prevent treatment 
interruptions.   
 
The Study Chair should be notified of any Grade 4 toxicity. 
 
6.11   Expected Toxicity 
 
6.111 Blood/Bone Marrow (Hematologic)  
 
 
Hematologic toxicity is seen infrequently unless pelvic RT is 
accompanied by chemotherapy. A CBC should be obtained 
weekly, and if the ANC is below 500/mcl or the platelet count 
drops below 50,000/mcl, counts should be obtained twice weekly. 
Even if chemotherapy is held for myelosuppression, radiotherapy 
should be continued as long as blood counts remain above critical 
values (See Section 6.12). 
 
 
Every effort should be made to maintain hemoglobin > 10g/Dl It is 
up to the individual investigator’s discretion as to how best to 
achieve this. 
 
6.112 Gastrointestinal 
 
Nausea and vomiting are rather unusual after pelvic RT. The use of 
prophylactic anti-emetics is strongly encouraged. Anti-emetic 
regimens are at the discretion of the investigator. Anti-emetics may 
be given when symptoms occur if not given prophylactically prior 
to treatment. 
 
Intractable nausea or vomiting is rarely seen with pelvic RT alone 
and is usually the result of another process (i.e., bowel 

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obstruction). Increased bowel activity with diarrhea usually can be 
controlled with low-fiber, low-fat, bland diets and anti-diarrheal 
medications. Should GI toxicity become severe, hospitalization 
may be required at which time the treatment may be interrupted 
temporarily until the patient’s condition improves. This 
interruption should be limited to < 1 week if possible, but no more 
than 2 weeks to remain on study.  
 
6.113 Renal/Genitourinary 
 
Acute toxicity of the urinary tract is manifested by cystitis. 
Maintaining high fluid intake is important. Bladder 
antispasmodics, analgesics and antibiotics are recommended. 
Gross hematuria is not usually seen with acute cystitis and suggests 
bladder invasion by tumor.  
 
6.114 Dermatologic/Skin (Cutaneous) 
 
With the use of megavoltage external beam RT skin reactions in 
the treatment field are infrequent. During RT, mild irritation and 
redness of the skin may occur within the radiation fields. Some 
patients may experience more intense skin reaction such as dry or 
moist desquamation depending upon the energy of the 
megavoltage beam, number of fields used per day, need to cover 
distal vagina and therefore flashing perineum and use of 
chemotherapy. Hair loss in the pubic area may occur which can be 
permanent. Late subcutaneous fibrosis, telangiectasia, and skin 
atrophy are uncommon sequelae. 
 
Acute skin reactions may be treated according to the institutional 
preferences. Aquaphor or steroid creams may be used for CTCAE 
Grade 1-2 reactions, and it is not necessary to interrupt the RT. For 
CTCAE Grade 3-4 skin reactions when generalized macular, 
papular or vesicular eruptions have developed, or there is 
generalized exfoliative or ulcerative dermatitis in the treatment 
fields, RT may be interrupted, but maximal supportive care should 
be used to avoid treatment breaks. 
 
Treatment may require symptomatic management of pain, use of 
warm saline soaks, vitamin A&D ointment, wearing loose 
clothing, and keeping the area dry. RT should be resumed as soon 
as the skin reactions have improved. 
 
 

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6.12 
Radiation Dose Modifications 
 
A maximum of up to 7 consecutive treatment days for RT break is allowed 
on protocol, but every effort should be made to minimize RT treatment 
delays and interruptions.  The radiation oncology study co-chair should 
be notified of any treatment break exceeding 7 days. 
 
6.121 Blood Bone Marrow (Hematologic) Adverse Effects  
External RT may be delayed for ANC < 250/mcl or platelet count 
< 30,000/mcl.  During an RT break for myelosuppresion, CBCs 
should be checked at least 2 times per week and RT restarted when 
counts exceed the threshold.   
 
6.122 Gastrointestinal Adverse Effects 
 
Patients will be treated with a low residue diet and anti-peristaltic 
drugs. External RT may be interrupted for CTCAE Grade 3 or 4 GI 
toxicity. Use of prophylactic anti-emetics is strongly 
recommended. 
 
6.123 Renal/Genitourinary Adverse Effects  
 
External RT may be delayed for CTCAE Grade 3 or 4 bladder 
toxicity.  
 
 6.124 Dermatologic/Skin (Cutaneous) Adverse Effects 
 
RT will not be delayed for moist desquamation, but a treatment 
break may be required for cutaneous ulceration. 
 
6.13 
Patients who must take a break longer than 2 weeks during radiotherapy 
will be removed from the protocol directed therapy. However, they should 
re-start radiotherapy off-study as soon as the toxicities have improved to 
an acceptable level.  
 
6.2  
Treatment Modification of Concurrent Chemotherapy  
 
 
Radiotherapy will not be omitted or delayed for chemotherapy-related toxicities  
 
unless the investigator considers that the patient is too unwell to be treated. Any  
 
interruption in radiotherapy due to toxicity requires a dose reduction of one level. 
 
 6.21  Cisplatin Modifications 
 
6.211  Gastrointestinal Adverse Effects 
 
6.2111 For nausea and vomiting, antiemetics should be used  
 prophylactically. 
 
6.2112 For nausea and vomiting requiring hospitalization or TPN > 

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24 hours, reduce cisplatin by one dose level. 
 
6.212  Renal/Genitourinary Adverse Effects 
 
6.2121 If creatinine rises to greater than 2.0 mg/Dl, discontinue 
cisplatin therapy. 
 
6.2122 Selective renal tubular defects are sometimes observed:  
 
 
Hypocalcemia with hypomagnesemia and hypokalemia are 
common and potentially severe. Replacement of 
magnesium, calcium and potassium are usually effective. 
Severe tubular effects, although rare, may require chronic 
replacement therapy. Diagnostic tests for alternative 
mechanisms of hypocalcemia (e.g. GI or metabolic) should 
be considered. 
 
6.213 Neurologic Adverse Effects 
 
6.2131 CTCAE Grade 1 - No change 
  
6.2132 CTCAE Grade 2 - Reduce cisplatin by one dose level 
 
6.2133 CTCAE Grade 3 or 4 - Hold cisplatin until recovered to ≤ 
grade 2 and then resume at one dose level reduction 
 
6.214 Blood/Bone Marrow (Hematologic) Adverse Effects  
 
Cisplatin should be withheld from patients with an ANC less than 
500/mcl or platelet count less than 50,000/mcl. Therapy should be 
delayed up to one week until these levels are exceeded.  
 
External RT should continue while drug is withheld, as long as 
thresholds for continued RT are met (see Section 6.12). 
 
6.215 Dose Modification Tables 
 
Dose Level 
Cisplatin 
Dose Level 1 
40 mg/ m2 (max = 70 mg*) 
Dose Level -1 30 mg/ m2 (max = 52.5 mg*) 
Dose Level -2 20 mg/ m2 (max = 35 mg*) 
 
 
 
* Max doses apply to those with BSA > 1.75 m2 
* There will be no dose-re-escalation after dose reduction 
 

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7.0 
STUDY PARAMETERS   
 
7.1 
Observations and Tests (06/13/2011) (05/12/2014) 
 
The following observations and tests are to be performed and recorded on the 
appropriate form(s): 
PARAMETER 
 
 
Prior to 
entry  
Weekly 
during 
Treatment 
Every 3 
months (1st 2 
years) 
Every 6 
months (3-5 
yrs) 
Annually 
Physical/Pelvic 
Examination 
1 
 
X 
X 
 
Toxicity Assessment 
4 
X 
X 
X 
 
Quality of Life 
Questionnaire 
X* 
2 
3 
 
 
Smoking Questionnaire 
1 
 
 
 
 
CBC/Diff/ platelets 
4 
5,6 
 
 
 
Creatinine, Alkaline 
phosphatase, SGOT, 
Bilirubin 
4 
5,7 
 
 
 
 
 
 
 
 
 
Follow-up CT or MRI or 
PET/PET-CT 
 
 
 
 
9** 
Chest Imaging (x-ray or CT 
scan of the chest) 
1 
 
 
 
8 
1. Within 28 days prior to initiating protocol therapy 
2. Three weeks and seven weeks following the first day treatment 
3. 9 months following the first day of treatment 
4. Within 14 days prior to initiating protocol therapy 
5. Must be drawn within 4 days of re-treatment 
6. If ANC < 500/mcl or platelet < 50,000/mcl, twice weekly 
7. Weekly in CRT group and monthly in RT group.  If Creatinine > ULN or Bilirubin > 1.5 x normal,     
    Alkaline phosphate and SGOT > 3 times normal, weekly  
8. Every 6 months for the first 3 years, then annually thereafter 
9. Every 6 months for the first 3 years, then annually thereafter, if chest imaging not already included     
    in surveillance CT, MRI, or PET/PET-CT. 
* QOL Questionnaire should be given prior to randomization 
** A CT of the chest/abdomen/pelvis or PET/CT is required within 30 days of documentation of any initial site of 
recurrence.  Other potential sites of recurrence will be reported as: 
I) 
Pelvic 
a) Vaginal mucosa 
b) Paravaginal/parametrial 
c) Lateral pelvic sidewall/pelvic nodes 
d) Posterior pelvis/presacral 
II) 
Extrapelvic 
a) Common iliac nodes 
b) Paraaortic nodes 
c) Other (specify, eg liver, lung, bone, peritoneum etc) 

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7.2 
STAINED PATHOLOGY SLIDE REQUIREMENTS FOR CENTRAL REVIEW 
TO CONFIRM ELIGIBILITY 
 
H&E stained pathology slides are required for central review by the GOG 
Pathology Committee to confirm eligibility for the protocol.  One or more 
representative H&E stained slide demonstrating the primary site, histologic cell 
type, grade, and most advanced stage of disease are required.  If the most 
advanced stage of disease is not documented by histology, the method of 
stage documentation needs to be stated (e.g. CT, MRI, etc.).   
 
In addition, representative H&E stained slide (or slides) will be required to 
document depth of cervical stromal invasion (see note below) and capillary-
lymphatic space involvement (if present).    
(Note:  Women will be dichotomized as having (1) positive capillary-
lymphovascular space involvement and one of the following: deep third 
penetration, middle third penetration and clinical tumor ≥ 2cm or superficial third 
penetration and clinical tumor ≥ 5 cm or (2) negative capillary-lymphovascular 
space involvement and middle or deep third penetration and clinical tumor ≥ 4 
cm. 
 
When submitting pathology material to the GOG Statistical and Data Center, 
individual slides must be labeled with GOG Patient ID, patient initials and the 
surgical / pathology accession number (e.g., S08-2355) and block identifier (e.g., 
A6).  Do not label the slides with disease site (e.g., right ovary) or procedure date.   
 
Pack the labeled slides into plastic slide cassette(s).  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, three copies of both the Pathology Form F (if required for 
the protocol) and the official pathology report in your own shipping containing 
using postal mail at your own expense directly to the Pathology Materials 
Coordinator at the GOG Statistical and Data Center, Roswell Park Cancer 
Institute, Research Studies Center, Carlton and Elm Streets, Buffalo, New 
York, 14263; phone (716) 845-5702.  The GOG Upload Application in SEDES is 
an alternative method for submitting pathology reports and Form F to the GOG 
Statistical and Data Center. Please see section 4.2 and 10.2 for additional 
requirements and instructions. 
 

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7.3 
TRANSLATIONAL RESEARCH 
 
7.31 
Specimen Requirements (05/12/2014) 
 
If the patient gives permission for her specimens to be collected and used 
for this optional translational research component, then participating 
institutions within the United States are required to submit the patient’s 
translational research specimens as outlined below (unless otherwise 
specified). 
 
Required Specimen 
(Specimen Code)  
 
Time Point 
Ship To 
 FFPE Primary Tumor 
(FP01)*  
• 1st choice: Block 
• 2nd choice: 16 Unstained 
Slides (charged, 5µm) 
Prior to all treatment 
GOG Tissue Bank within 8 weeks of 
registration1 
 
 
Whole Blood (WB01) 
7-10Ml drawn into 
purple-top (EDTA) 
tube(s) 
Prior to or after starting treatment  
GOG Tissue Bank the day the 
specimen is collected 
 
 
*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-0263, 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 (05/12/2014) 
 
FFPE tumor and DNA extracted from whole blood will be banked for 
future research.  
 
7.33 
Future Research (05/12/2014) 
 
Details regarding the banking and use of translational research specimens 
for future research can be found in Appendix II.  
 
7.4 
Quality of Life Research 
 
Please see sections 4.5 and 4.6 for information regarding the QOL assessments for 
this protocol and a description of the time points for these assessments.  Specific 
information about the assessment time points and proper administration of the 
QOL questionnaires is out lined below. 
 
 

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Time Points for Quality of Life Data Collection 
 
 
Prior to 
randomization 
At 3 weeks*+ 
7 weeks* 
9 months* 
One Scantron form with 52 
Questions.  
FACT-Cx (42),  
Neurotoxicity questions 
(4), 
Additional toxicity 
questions (5),  
brief pain question (1). 
 
X^ 
X 
X 
X 
 
 
 
 
^ Within 28 days prior to initiating protocol therapy 
* Following first day of treatment.    
+ In women receiving cisplatin chemotherapy the QOL assessment 3 weeks following the first 
day of treatment should be done prior to starting a cisplatin cycle. 
 
7.41  If a patient progresses or is removed from the study treatment for any 
reason, continue to follow the schedule of QOL assessments when 
possible regardless of subsequent treatments.  Whenever possible, QOL 
questionnaires should be administered at the clinic visit before the patient 
is seen by the physician and before evaluations or test results are shared 
with her.  In the event that the questionnaires are not administered at the 
clinic visit, the QOL data can be collected by telephone or mail as back-up 
methods, with telephone data collection being the preferred back-up 
method. 
 
7.42 
The Quality of Life Liaison (Nurse/Data Manager) at each institution has 
overall responsibility for the administration of the study questionnaire. 
 
7.43 
The Nurse/Data Manager should read the instructions printed on the 
questionnaire to the patient and ensure the patient understands the 
instructions.  It is important to assure the patient that all material on the 
questionnaire is confidential and will not be shared with the health care 
team and that it will not become part of the medical record. 
 
7.44  Assistance in reading the questionnaire is permitted if the patient is unable 
to complete the questionnaire on her own (e.g., difficulty in reading, 
elderly).  It is important not to influence the response of the patient 
 
7.45 
Patients should be instructed to answer all the questions regardless of 
whether the symptoms or conditions asked about are related to cancer or 

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cancer treatment.  Discourage family members from being present during 
questionnaire completion or from influencing the patient’s response. 
 
7.46 
Review the questionnaire for completeness before the patient leaves the 
clinic/office. 
 
7.47 
If the patient has marked more than one answer per question, ask the 
patient which answer best reflects how she is feeling. 
 
7.48 
It is essential that the questionnaires be completed according to the 
schedule described in Section 7.1 and in the above table. 
 
7.49 
If the patient refuses or cannot complete the questionnaire at any time 
point, she should be asked to do so at the next scheduled administration 
time. 
 
 

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8.0 
EVALUATION CRITERIA   
 
8.1 
Outcome Measures  
 
 
The major parameters of outcome are recurrence-free survival and overall   
 
survival.  
 
8.11  Recurrence is defined as clinical, radiological or histological reoccurrence 
of disease since study entry.  
 
8.111 Site of First Recurrence (e.g. para-aortic or supraclavicular lymph 
nodes, lung, liver, bone, etc.) will also be documented.  
 
8.12  Recurrence Free Survival is defined as the date from protocol registration 
to date of first documented recurrence, death or date of last contact.  
 
8.13 
Overall Survival will be defined as observed length of life from entry into 
the study to death; or for living patients, the date of last contact regardless 
of  whether or not this contact is on a subsequent protocol.  
 
8.14  Subjective Parameters including performance status, specific symptoms, 
and side effects are graded according to the active version of CTCAE. 
 
 
 

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9.0 
DURATION OF STUDY    
 
 
9.1 
Each patient should complete the study treatment unless disease recurrence occurs 
or toxicity prohibits further therapy.  
 
9.2 
Each patient should be followed quarterly for two years and every six months for 
three additional years, and thereafter annually or at the time of recurrence until 
death. 
 
 

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10.0 
STUDY MONITORING AND REPORTING PROCEDURES   
 
10.1 
ADVERSE EVENT REPORTING FOR ALL REGIMENS (COMMERCIAL 
AGENTS AND RADIATION THERAPY ADMINISTRATION) (05/12/2014) 
   
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.  
 
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.h
tm).  
All appropriate treatment areas should have access to a copy of the CTEP 
Active Version of CTCAE. 
 
A copy of 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 or commercial 
agents, and role of the pharmaceutical sponsor, an 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 Adverse 
Event Reporting System (CTEP-AERS).  All CTEP-AERS submissions 
are reviewed by GOG before final submission to CTEP.  Submitting a 
report through CTEP-AERS 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 AE’s 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 AE’s 
to the NCI.  In compliance with FDA regulations, as contained in 21 CFR 
312.64, AE’s should be reported by the investigator. 
 

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10.13 Phase 2 and 3 Trials Utilizing a Commercial Agent:  CTEP-AERS 
Expedited Reporting Requirements for Adverse Events That Occur Within 
30 Days of the Last Dose of Any Commercial Study Agent  
 
 
Reporting Requirements for Adverse Events that occur within 30 Days¹ of the Last Dose of the 
Commercial Agent on Phase 2 and 3 Trials 
 
 
Grade 1 
 
Grade 2 
 
Grade 2 
 
Grade 3 
 
Grade 3 
Grades 
4 & 52 
Grades 
4 & 52 
Unexpected  
and Expected 
 
 
Unexpected 
 
 
Expected 
Unexpected 
Expected 
Unexpected Expected 
With  
Hospitali-
zation 
Without 
Hospitali- 
zation 
With  
Hospitali- 
zation 
Without 
Hospitali- 
zation 
Unrelated 
Unlikely 
Not 
Required 
Not 
Required 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
7 
Calendar 
Days 
Possible 
Probable 
Definite 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
7 Calendar 
Days 
7 Calendar 
Days 
Not 
Required 
24-Hrs; 
3 Calendar 
Days 
7 
Calendar 
Days 
1 Adverse events with attribution of possible, probable, or definite that occur greater than 30 days after the 
last dose of treatment with a commercial agent require reporting as follows: 
CTEP-AERS 24-hour notification followed by complete report within 3 calendar days for: 
• Grade 4 and Grade 5 unexpected events  
      CTEP-AERS 7 calendar day report: 
• Grade 3 unexpected events with hospitalization or prolongation of hospitalization 
• Grade 5 expected events 
 
2 Although Actep-AERS 24-hour notification is not required for death clearly related to progressive disease, a 
full report is required as outlined in the table. 
 
 Please see exceptions below under the section entitled, “Additional Instructions or Exceptions to CTEP-AERS 
Expedited Reporting Requirements for Phase 2 and 3 Trials Utilizing a Commercial Agent.”          March 2005 
 
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 CTEP-
AERS within 24 hours of learning of the event followed by a complete CTEP-AERS 
report within 3 calendar days of the initial 24-hour report. 
“7 calendar days” – A complete CTEP-AERS report on the AE must be submitted within 
7 calendar days of the investigator learning of the event. 
 
• 
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. 
 

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• 
Any event that results in persistent or significant disabilities/incapacities, congenital 
anomalies, or birth defects must be reported to GOG via CTEP-AERS if the event occurs 
following treatment with a commercial agent. 
 
• 
Use the NCI protocol number and the protocol-specific patient ID provided during trial 
registration on all reports. 
 
Additional Instructions or Exceptions to CTEP-AERS Expedited Reporting Requirements for 
Phase 2 and 3 Trials Utilizing a Commercial Agent: 
 
• All Grade 2, 3, and 4 myelosuppression (including neutropenia, anemia, and 
thrombocytopenia) that does not require hospitalization is exempt from expedited 
reporting. 
 
10.14 Procedures for Expedited Adverse Event Reporting: 
 
10.141 CTEP-AERS Expedited Reports (06/13/2011):  
 
Expedited reports are to be submitted using CTEP-AERS 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 CTEP-AERS (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) Myelodysplatic syndrome, or 3) 
Treatment related secondary malignancy. 
 
In the rare occurrence when Internet connectivity is disrupted a 24-
hour notification is to be made to GOG by telephone at 215-854-
0770.  An electronic report MUST be submitted immediately upon 
re-establishment of internet connection. Please note that all paper 
CTEP-AERS forms have been removed from the CTEP website 
and will NO LONGER be accepted. 
 
10.15 Automated CDUS reporting  
 
For studies using commercial 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 AE’s reported through CTEP-AERS will also be included 
with the quarterly CDUS data submissions.   
 
 
 

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10.2  GOG DATA MANAGEMENT FORMS 
 
The following forms must be completed for all patients registered and submitted 
to the GOG Statistical and Data Center (SDC) in accordance with the schedule 
below. Protocol forms and instructions can be submitted through or printed from 
the SDC Electronic Data Entry System (SEDES) online application found at the 
GOG Web Menu page.  All amendments to forms submitted through SEDES 
must also be submitted through SEDES.  The original form and required copies 
for forms NOT submitted online must be mailed to the GOG SDC.  Pathology 
material (Form F, pathology reports and slides) should be submitted together 
via mail. The GOG Uploader Application in SEDES is an alternate method 
for submitting the operative report, discharge summary, Form F and 
pathology reports to the GOG SDC. Additionally radiation materials (forms, 
copies, films, reports, etc) must be submitted together via postal mail. 
 
Form± 
Due within 
Copie
s* 
Comments 
Weeks 
Event 
Form R (Registration Form) 
 
2 
 
Registration 
 
1 
 
Mandatory submission via 
SEDES 
Form OSC (Primary Cervical 
Cancer On Study Form) 
2 
Registration 
1 
Mandatory submission via 
SEDES 
Specimen Consent 
Application 
1 
Registration  
NA 
(05/12/
2014) 
Mandatory submission via 
SEDES (05/12/2014) 
Form DR (Pre-Treatment 
Summary Form) 
2 
Registration 
1 
Mandatory submission via 
SEDES 
Hysterectomy and Pelvic 
Lymphadenectomy: 
 
Form C (Surgical Reporting 
Form) 
 
Operative Report 
Discharge Summary 
 
 
 
4 
 
 
4 
4 
 
 
 
Registration 
 
 
Registration 
Registration 
 
 
 
1 
 
 
2 
2 
 
 
 
Mandatory submission via 
SEDES 
 
Submit via postal mail or 
upload via SEDES. 
Primary disease:  
   Diagnostic Biopsy: 
Form F (Pathology Form) 
Pathology Report  
Stained Slides 
Hysterectomy and Pelvic 
Lymphadenectomy: 
  Form F (Pathology Form) 
   Pathology Report  
   Stained Slides  
 
 
6 
6 
6 
 
 
6 
6 
6 
 
 
Registration 
Registration 
Registration 
 
 
Registration 
Registration 
Registration 
 
 
2** 
3** 
** 
 
 
2** 
3** 
** 
Submit together via postal 
mail to GOG SDC in Buffalo, 
New York or submit using 
the report upload to SEDES. 
 
 
Form SHQ (Smoking History 
Questionnaire) 
2 
Registration 
1 
Mandatory submission via 
SEDES 

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Quality of Life Scantron 
Form:  
 
Form – baseline assessment 
Form –  3 week assessment 
Form – 7 week assessment 
Form – 9 month assessment 
 
 
2 
5 
9 
41 
 
 
 
Registration 
Treatment Start 
Treatment Start 
Treatment Start 
 
 
 
1 
1 
1 
1 
 
 
 
Submit Original Scantron 
Form via postal mail to GOG 
SDC in Buffalo, New York 
Radiation Materials: 
External beam: 
 simulation films or 
digitally    reconstructed 
radiograph  
 portal films 
 daily treatment records 
 CT/MRI showing  
relevant target volume 
 dosimetry calculations 
 Isodose distribution       
curves 
 Form G (Radiation 
Treatment Form) 
 3D Plan  
 
IMRT Rapid Review (See 
Section 4.31) must submit all 
the required data for IMRT as 
stated below prior to 
treatment of patient. 
 
IMRT: 
IMRT Treatment Plan 
electronically submitted to 
ITC. 
The IMRT Treatment Plan 
should include: 
 CT/MRI showing  
relevant target volume 
 dosimetry calculations 
 Dose Volume 
Histograms (DVH) 
 
4 
Completion of  RT 
 
 
 
1 
 
1 
2 
1 
 
2 
2 
 
1 
 
2 
Form G must be submitted 
via SEDES.  Paper copies 
should also be submitted with 
radiation materials via postal 
mail. 
 
 
 
 
 
 
 
 
 
 
 
Submit electronically to the 
ITC (http://atc.wustl.edu) 
 
 
 
 
Submit electronically to the 
ITC (http://atc.wustl.edu) 
Form D2R (Cycle Dose Drug 
Form) 
 
2 
Completion of each cycle 
of therapy on Regimen II 
1 
Mandatory submission via 
SEDES 
Form T (Common Toxicity 
Form) 
2 
Regimen I: three weeks 
after completion of RT  
 
Regimen II: Start of each 
subsequent cycle and 3 
weeks after last cycle  
1  
 
Mandatory submission via 
SEDES 

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Form SP-FP01-0263*** FFPE 
primary (05/12/2014) 
8 
Registration 
 
NA 
(05/12
/2014) 
Mandatory submission via 
SEDES ƒ 
(05/12/2014) 
Form SP-WB01-0263  
whole blood (05/12/2014) 
8 
Registration 
 
NA 
(05/12
/2014) 
Mandatory submission via 
SEDESƒ 
(05/12/2014) 
Form Q0 (Treatment 
Completion Form) 
 
2 
Completion of study Rx 
and change in Rx 
1 
Mandatory submission via 
SEDES 
Form TLC (Follow-Up Period 
Adverse Event Reporting 
Form) 
2 
Each follow-up toxicity 
assessment following 
completion of study 
therapy 
1 
Mandatory submission via 
SEDES 
 
Form Q (Follow-Up Form) 
 
2 
Disease progression; 
death; normal follow-up 
1 
Mandatory submission via 
SEDES 
quarterly for 2 years, semi-
annually for 3 more years, 
and annually thereafter  
* 
The number of required copies including the original form which must be sent to the Statistical and Data 
Center. 
** 
At least one representative H&E stained slide (or slides) demonstrating primary site, histologic cell type, and 
grade, and one H&E stained slide showing the most advanced stage of disease will be required.  In addition, 
representative H&E stained slide (or slides) will be required to document depth of cervical stromal 
invasion and capillary-lymphatic space involvement.  See Sections 4.2 and 7.2 for additional details and 
instructions for submitting this material. 
*** 
A copy of the corresponding pathology report must be shipped with all tissue specimens sent to the GOG 
Tissue Bank.(05/12/2014) 
ƒ 
Form SP must be submitted regardless of whether the specimen is submitted for research. (05/12/2014) 
±  
Use the SDC Electronic Data Entry System (SEDES), available on the GOG website, to view and print a 
copy of each form along with instructions, and to submit forms electronically.  Please check SEDES 
periodically as forms that are not currently available for electronic data entry will be made available for 
electronic data entry over time. 
 
 
This study will be monitored by the Abbreviated Clinical Data System (CDUS) Version 3.0 
CDUS data will be submitted quarterly to CTEP by electronic means. 
 
 
 
 

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11.0   STATISTICAL CONSIDERATIONS (03/05/18) 
 
11.1 
Study Design and Registration 
This study is designed as a randomized (allocation ratio is 1:1) Phase III clinical 
trial of adjuvant RT (control arm) versus weekly cisplatin concurrent to RT in 
post-operative intermediate risk Stage I-IIA cervical cancer patients. Intermediate 
risk patient characterization is based on three post-surgical prognostic factors 
namely, capillary lymphatic space (CLS) involvement, stromal invasion and 
tumor size.5, 17, 40,41  (14-MAR-2022). 
 
Prior to registration (and randomization) patient eligibility will be reviewed and 
verified using a study specific fast fact sheet (FFS). All patients on this study will 
be registered (and randomized) centrally at the GOG Statistical and Data Center 
(SDC).  
 
 
Treatment assignments will be concealed from institutions and patients until the 
registration process is completed. Randomization will be balanced within five 
stratification factors; CLS involvement (positive or negative), stromal invasion 
(deep, middle, superficial), performance status (0/1, 2), RT modality (XRT, 
IMRT) and cooperative group (KGOG, GOG). A dynamic allocation 
(minimization) randomization algorithm with equal probabilities to the two 
treatment arms within strata will be used to facilitate optimal balance between 
arms.42  
 
11.2 
Study Objectives 
 
The translational research (TR) objective is to collect specimens for future 
research. Valid patient outcome endpoints will be used to assess primary, 
secondary and Quality of Life (QOL) objectives. Recurrence free survival (RFS) 
is recognized as the primary study endpoint. 
 
11.21   Primary objective 
 
To determine if post-operative adjuvant CRT therapy improves RFS when 
compared to RT alone in post-operative intermediate risk stage I-IIA 
cervical cancer patients 
 
11.22 Secondary objectives 
 
11.221 To determine if post-operative adjuvant CRT therapy improves 
overall survival (OS) when compared to RT alone in post-
operative intermediate risk stage I-IIA cervical cancer patients 
 
11.222 To summarize and compare differences in frequency and severity 
of therapy attributed adverse events (according to the active 
version of CTCAE) between treatment arms 

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11.223 To provide assessment of patient risk- benefit (positive study only) 
 
11.23 QOL Objective 
 
  
 
To determine whether post-operative adjuvant CRT improve the health 
related QOL and produce favorable toxicity profiles compared to RT 
alone. 
 
11.3 
Data Elements and Endpoints 
The following data elements and endpoints will be used to determine the relative 
therapeutic treatment effect of the two regimens: 
 
11.31 Outcome variables: recurrence-free survival (RFS), overall survival (OS) 
and local control (LC).  RFS will be the primary endpoint. 
 
11.32 Baseline disease characteristics: FIGO stage (I or IIA), tumor grade, cell 
type (squamous, adenosquamous or adenocarcinoma), capillary lymphatic 
space tumor involvement (positive/negative), clinical tumor size and 
extent of stromal invasion (deep 1/3, middle 1/3 or superficial 1/3). 
 
11.33 Site(s) of recurrence: local (pelvis regions, including vaginal) or distant 
(abdomen, lung, bone, brain and other). 
 
11.34 Patient characteristics: age, performance status, race and ethnicity. 
 
11.35 Frequency and severity of adverse events as assessed by the active version 
of CTCAE. 
 
11.36 Treatment compliance: Number of cycles and amount of CRT 
administered, treatment span, incidence and duration of treatment delays, 
reason for delays, and reason why off study therapy. 
 
11.37 Health related QOL metrics: FACT-Cx TOI for cervix cancer patients, 
FACT-GOG/Ntx4 subscale (four items) for neuropathy symptoms, BPI 
single item for pain, and five additional toxicity questions 
 
11.38 Smoking history: prevalence of active smoking and extent of nicotine 
dependence.   
 
11.4 
Accrual 
The anticipated annual accrual (based on GOG-0092 and the Korean Gynecologic 
Oncology Group (KGOG) experience is 120 patients (24 and 96 from GOG and 
KGOG treatment centers respectively). Power analysis and sample size 
calculations (see Section11.5), suggests this study will require at least 480 eligible 
and evaluable cases.  

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                        Update (11/2017): As of November 2017, the observed annual accrual is 
approximately 36 patients, smaller than the anticipated annual accrual of 120 
patients. Accounting for this slower accrual, the study will now require at least 
342 eligible and evaluable cases without any changes to the study operating 
characteristics. 
 
                        Update (03/2022): As of January 2022, GOG-0263 accrued 338 patients, with an 
overall average accrual rate of 2.4 patients per month. Accrual has declined 
considerably since 2019 (see Figure 1) averaging 1.7 patients per month from 
1/1/2019 to 2/29/2020, and 0.76 patients per month from 3/1/2020 to 1/7/2022. 
On this basis, accrual is being permanently suspended. (14-MAR-2022) 
 
Figure 1 
Cumulative Accrual for GOG 0263 - Data as of 1/7/2022 
 
 
     
11.5 
Hypothesis, Planning Parameters and Sample Size 
The “design” hypothesis is based on the primary objective to determine if post-
operative adjuvant CRT can significantly improve 3 year RFS in intermediate risk 
stage I-IIA cervical cancer patients when compared with adjuvant RT alone (1-
sided alternative hypothesis). The log-rank test will be the primary significance 
test.43 
 
Previous studies including GOG-0092 suggests a significant proportion of 
patients on this study will be cured.17 Thus, to model the expected performance of 

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the control arm we assume the Gompertz ~ (γ ,θ ) survival probability distribution 
with initial hazard γ  and hazard dissipation θ .44-47  
 
Equations 1, 2, and 3 lists survival, hazard, and cure rate functions respectively 
under the Gompertz ~ (γ ,θ ) survival probability distribution assumption. 
 
 
 
 
[
]



≥




−
=
elsewhere
0
0
for 
)
exp(
1
exp
)
(
t
t
t
S
θ
θ
γ
 
 
(1) 
 
 



≥
=
elsewhere
0
0
for 
)
exp(
)
(
t
t
t
h
θ
γ
 
 
 
(2) 
 
 
 
 
 
 




=
θ
γ
π
exp
  
 
 
 
 
(3) 
 
Naturally we derived parameter estimates
MLE
ˆγ
 and 
MLE
ˆθ
 using the outcome data 
of  GOG-0092 RT arm, since this historic information came from patients whose 
disease and treatment profiles best mimics the control arm.17 As a result, the 
anticipated performance (primary endpoint) of this study’s control arm was 
estimated by substituting the calculated 
MLE
ˆγ
 and 
MLE
ˆθ
into equation (1) at several 
time points.  Similarly, using equation (3) the expected cure rate (
MLE
ˆπ
) for the 
control arm was deduced. 
 
Derived parameter estimates and expected cumulative probability of recurrence 
(ECPR) for the control arm at 12, 36, and 60 months are listed in Table 11.1.  
                                
Historic Data 
(GOG-0092 RT arm) 
       Control Arm   
MLE
ˆγ
 
MLE
ˆθ
 
MLE
πˆ
 
Time (months) 
12 
36 
60 
0.0068 -0.0315 0.8058 ECPR 
0.0657 0.1362 0.1674 
 
 
 Table 11.1 
 
Figure 11.1 shows superimposed plots of the expected and empirical cumulative 
probability of disease recurrence consistent with the estimated Gompertz model 
(solid curve) and the outcome data from GOG-0092 RT arm (dash curve) 
respectively. 
 
 
 
 
 
 
 
 
 

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            Figure 11.1 
 
11.51 Minimum Detectable Difference 
 
A change in RFS of 6.3% (i.e. from 87% to 93.3%) is considered a 
clinically important treatment advantage to detect. This difference 
translates into a relative hazard ratio of 0.4980 for increasing the RFS. 
This difference will require a total 36 recurrences in the control arm to 
afford statistical power (probability of a true-positive study) of at least 
0.80 when keeping the probability of type I error (one tail test) at 
significance level, α =0.05.47 The expected total number of recurrences 
conditioned on the alternate hypothesis is 54.47 – 49 
 
 11.52 Sample Size 
 
Power analysis and sample size calculations using the Gompertz model 
suggest that enrolling at least 480 eligible and evaluable patients will 
result in the required number of recurrences.  
 
 
Assuming uniform accrual and 10% lost to follow-up, the targeted accrual 
is 534 patients over 54 months. The study will be considered sufficiently 
mature for final analysis of the primary endpoint (RFS) when there are at 
least 36 events (recurrences) in the control arm. Conditioned on the 
anticipated rate of recurrence on the control arm, the post accrual follow-
up period will be at least 18 months.47, 48. The timing for OS assessment 
will coincide with the primary analysis of RFS (see Section 11.3). 
 
            Update (11/2017): Based on the observed accrual rate through November 
2017, power analysis and sample size calculations using the Gompertz 
model suggest that enrolling at least 342 eligible and evaluable patients 
will result in the required number of recurrences without any changes to 
the study operating characteristics.  Assuming uniform accrual with 5% 

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ineligible proportion estimated from this study, the targeted accrual is 360 
patients expected to be met in 2020. The study will be considered 
sufficiently mature for final analysis 
            of the primary endpoint (RFS) when there are at least 54 RFS events 
observed among all patients. Conditioned on the anticipated rate of 
recurrence on the control arm, the post accrual follow-up period will be at 
least 24 months.47, 48 
  
Update (03/2022): Due to very slow accrual since 2019, enrollment is 
being permanently suspended. As of March 11, 2022, 340 patients 
enrolled onto GOG-0263, of whom 311 were eligible. The study will be 
considered sufficiently mature for final analysis of the primary endpoint 
(RFS) when at least 54 RFS events are observed among all patients. Given 
the anticipated rate of recurrence on the control arm, the post accrual 
follow-up period will be about 40 months. (14-MAR-2022) 
 
11.6 
Analyses and Evaluation of Study Endpoints 
 
By definition the intent to treat (ITT) analysis set consists of all randomized 
patients.49-51 However, it is possible, after randomization, for a given case to be 
excluded (upon centralized GOG reviews) for a variety of reasons including, 
incorrect baseline risk assessment, inadequate pathology, wrong stage, and 
improper surgery. On GOG-0092, approximately 7% of randomized cases were 
excluding upon either gynecologic or pathologic central reviews.  
 
 
Despite being randomized (and possibly treated), excluded cases will not be 
included in the analysis of RFS or OS. Thus, for evaluation of primary endpoints 
we define the modified intent to treat (MITT) analysis set to include all eligible 
and evaluable patients as randomized. 
 
 
Regarding the assessment of AE objectives, in additional to utilizing the MITT 
set; analyses will also be conducted on all randomized patients as treated.  
 
11.61 Evaluation of RFS and OS 
 
Product-limit estimates according to the method of Kaplan and Meier and 
the one sided log-rank test (α =0.05) will be used to compare survival 
endpoints (RFS and OS) between treatment arms.43, 53, 54 
 
 
Gompertz hazard regression will be employed to evaluate relative risk 
(hazard ratio) and cure rates, adjusting for known prognostics factors. It is 
plausible to used the infamous Cox proportional hazard regression, the 
advantage of the Gompertz approach is its provision of estimates of the 
cure rate.47, 55 
 
11.62 Evaluation of Site(s) of Recurrence  
 
The site(s) of first disease recurrence will be classified as: pelvic-only, 
extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment 

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group. The test of the hypothesis that the probability of local failure is 
independent of randomized treatment will be assessed with Exact Logistic 
Regression adjusted know prognostic factors.56 
 
11.63 Toxicity analysis   
Adverse events will be graded according to the active version of CTCAE 
(Grades 0 - 5), but combining Grades 0, 1 and 2 data. In addition to 
displaying frequency of AE for each grade category, significance of 
observed differences between treatment arms within each AE category 
(e.g. GU, GI HM will be analyzed using Fishers’ exact test.57 
 
11.64 Health related QOL: 
 
 
Health related QOL will be assessed using a one page form, made up of 52 
questions: the FACT-Cx (42), Neuro-toxicity questions (4), additional 
toxicity questions (5), and pain question (1).  
 
 
The pain question is scored using an 11 point integer scale (from 0 = no 
pain to 10 = the worst pain). All other questions are scored using a 5 point 
scale (0 = not at all; 1 = a little bit, 2 = somewhat; 3 = quite a bit; 4 = very 
much). 
 
 
 
11.641 QOL assessment time points: 
 
Each patient will complete the QOL questionnaire at the following 
time points regardless of the amount of study therapy received 
 
T0: baseline, just prior to entry/randomization 
 
T1: 3 weeks from planned (or actual) treatment start date  
 
T2: 7 weeks from planned (or actual) treatment start date 
 
T4: 36 weeks from planned (or actual) treatment start date 
 
11.642 Construct and scoring: 
 
The Treatment Outcome Index of the Functional Assessment of 
Cancer Therapy for cervix cancer (FACT-Cx TOI) is a subset of 
the FACT-Cx defined to assess general changes in QOL of cervix 
cancer patients. It consists of three subscales: Physical well-being 
(7 items), Functional well-being (7 items) and Cervix Cancer 
subscale (15 items).  
 
 
 
 
 
The FACT/GOG Ntx4 subscale (i.e. the four neuro-toxicity 
questions) shown to be most related to cisplatin based 
chemotherapy will be used in this study. Regarding worst pain 
experiences, one question (the pain question) from the Brief Pain 
Inventory (BPI) will be asked.  Within an individual assessment, 
one or more items may not be answered. A subscale score will be 
computed as long as more than 50% of subscale items have been 
answered. A subscale score Si with Ni items  will be calculated as: 
 

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(
)
∑
∑
=
=
×
×
=
1
1
j
ij
j
ij
ij
i
i
s
N
S
δ
δ
 
 
11.643 Where δij is equal to 1 when the jth item has a valid response, 
otherwise it is equal to 0 and sij is the response score of the jth item. 
The total FACT-Cx TOI score is the sum of the subscale scores if 
at least 80% of the FACT-Cx TOI items provide valid answers. 
The FACT-Cx TOI, and the FACT-GOG/Ntx4, total scores ranged 
0 – 116, and 0 – 16 respectively. 
 
11.644  QOL hypotheses and analyses: 
The principal QOL research question is, are there differences in 
general QOL as determined with the FACT-Cx TOI, or in 
neuropathy symptoms as assessed by the FACT-GOG/Ntx 
subscale scores or in pain as assessed with the single item BPI 
question scores, between treatment arms: 
H0: QSARM 1 = QSARM 2 
  
 
 
 
Where QS (.) is a vector of expected FACT-Cx TOI, FACT-
GOG/Ntx4 and scores evaluated at specific time points for the 
patients on the indicated arms.  
 
Regression models will be used to evaluate the hypothesis on the 
FACT-Cx TOI, and the FACT-GOG/Ntx4 subscale, adjusting for 
baseline FACT-Cx TOI scores and age.  
 
QOL analyses using the pain question and the five additional 
toxicity questions will be considered exploratory, and 95% 
confidence interval will be reported for observed differences 
between treatment arms. 
 
11.645 Power Analysis for QOL:  
Since the primary QOL hypothesis (H0) includes two primary QOL 
endpoints; the overall type 1 error rate can become large if the 
significant level for each endpoint of the hypothesis is set at 5%. 
To control the overall type I error rate at 5%; the significance level 
is set at 0.025 (0.05/2) using the Bonferroni method. 
The accrual objective of this study is 342 eligible patients (171 per 
arm).  
 
Based previous and current GOG studies QOL compliance is 
estimated to be at least 75% for all assessment points. Therefore 
the number of patients that will complete the QOL assessments at 

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each time point is estimated to be at least 128 eligible patients per 
arm. Assuming that QOL compliance is ≥75%, this study will be 
able to detect a difference of 0.5 standard deviation (SD) in QOL 
scores as measured by the FACT-Cx TOI and the FACT-
GOG\Ntx4 subscale with at least 95% power at α = 0.025 ( two-
sided ). 
 
11.7 
Study Monitoring, Data Quality Control and Semi-annual Reports (05/12/2014)  
The GOG SDC is responsible for the secure, efficient and accessible storage of 
the data.  To assure the best possible data quality, the study statistician in 
collaboration with the data manager/coordinator (DM) will execute regular data 
checks. Inconsistencies and errors will be queried and sites will notify the DM 
upon resolution. In turn the DM will repeat data checks to make certain that query 
was indeed resolved. Every effort will be made to resolve outstanding queries 
promptly. Unresolved queries will be documented and briefly cited in the study 
scientific table.   
 
CRFs will be reviewed by the study chair (co-chair) in May and November of 
each year of active accrual. Addition reviews may be scheduled in conjunction of 
interim futility and efficacy analyses. The purpose of these reviews is to access 
protocol compliance and possibly make recommendations.  
 
After data checks, study chair (co-chair) reviews and data updates, a locked 
dataset void of protected patient information will be saved using standardized 
GOG SDC dataset achieving convention.  
   
 
 
Reports, with treatment assignment blinded, will be generated periodically from 
the most recent locked information by the study statistician for inclusion into the 
GOG’s Semi-annual Statistical Report (GOG SR).  The SR is distributed to GOG 
members at the GOG Semi-annual Business Meeting and it is made available to 
group members via the GOG Website. The purpose is to access study progress 
regarding accrual (and patient accession), distribution of baseline traits, treatment 
compliance, patient safety (adverse events) and to facilitate the formulation of 
possible amendments as needed.  
 
In addition to these reports, all serious (SAE) and unexpected adverse events 
regardless of attribution will be communicated promptly to the study chair, and 
any regulatory agencies mandated in the protocol. Furthermore, toxicity 
information will be reviewed by the GOG Safety Review Committee (SRC) at 
each semi-annual meeting during the period for which patients are on study. 
 
The goal of the SRC is to review the AE data, including all new SAE reports 
(from ongoing GOG studies) submitted between consecutive GOG business 
meetings held in January and July each year.  
 

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In addition to the SRC, the study will also be supervised by the GOG Data Safety 
and Monitoring Board (DSMB).  This group is charged with monitoring ongoing 
trials for early and convincing evidence of clinically important benefit or early 
evidence of harm. The DSMB may recommend that the trial continue as planned, 
be amended or be terminated (cease accrual) early. In general, the SRC reports to 
the DSMB.  
 
11.8 
Interim Analyses 
 
11.81 Interim Safety Analysis (05/12/2014) 
Each GOG SR for this study will include a safety analysis made up of a 
detail listing of the maximum grade for any AE attributed to therapy by 
blinded treatment. Significance of AE imbalance between treatment arms 
will be accessed informally or formally (e.g., Fisher exact test) according 
to the available information. Treatment assignment will be revealed to 
either one of respective data monitoring committees (SRC or DSMB) 
upon request. 
 
11.82 Interim Analysis for Efficacy 
 
Two interim analyses of RFS will be conducted just before the GOG semi-
annual business meeting that reports for the first time at least 12 and 24 
recurrences are observed in the control arm (i.e., approximately 33% and 
67% of information needed for final analysis). Consideration will be given 
to stopping the trial at if dramatic differences in RFS are observed 
between the two treatment arms. The interim log-rank test of RFS will be 
adjusted for known prognostic factors. 
 
            Update (11/2017): The 1st planned interim analysis was performed at the 
33% of the information time (i.e., 18 RFS events observed in both arms 
out of the 54 RFS events required in both arms). The 2nd planned interim 
analysis will be conducted at 67% of the information time (i.e., 36 RFS 
events observed in both arms out of the 54 RFS events required in both 
arms). This switch from the number of RFS events observed only in the 
control arm to the number of RFS events observed in both arms will not 
change the study operating characteristics, the pre-specified interim 
analyses’ information time, and the pre-specified stopping rule for efficacy 
and futility.  
 
 
 
The interim stopping rule assumes that three sequential tests are made 
using the O’Brien-Fleming spending functions to determine the test 
boundaries.58, 59 If the null hypothesis can be rejected terminating accrual 
will be considered. The critical z-scores at interim analysis are z = 3.2003, 
z = 2.1409 and z = 1.6948 corresponding to 33%, 67% and 100% (final 
analysis) of the information time respectively. The tail probabilities 
associated with these z-scores are 0.0007, 0.0161 and 0.0451 respectively. 
This stopping rule will maintain the overall type I error for this one-sided 

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log-rank test at 0.05. (14-MAR-2022) 
 
11.83 Interim Futility Analysis 
 
If there is any degree of excess risk of recurrence in the experimental arm 
compared to the control arm then accrual will be terminated with a 
conclusion that the experimental arm did not exhibit a RFS advantage.60 In 
this event, the null hypothesis will be accepted. The acceptance region 
during interim analysis at 33% of the information time will be z < 0 and at 
final analysis, z < 1.6948. This stopping rule increases the probability of 
type II error by 2.3%. 
 
 11.84  Suspending Follow-up for the Final Analysis (03/2022) (14-MAR-2022)            
The RFS endpoint is expected to mature about 40 months after the 
recommended early closure (Table 11.1).      
  
            To ensure timely and efficient dissemination of the study results, follow-
up for the primary RFS analysis may be suspended 24 months after the 
last patient is enrolled on the study. If the primary endpoint has not 
matured by this time, the DMC may recommend closing the study for 
analysis. This decision will be informed by the number of events observed 
to date, the number of patients still at risk, the estimated RFS hazard, and 
other factors as appropriate.  
 
           Table 11.1 shows the projected time for final analysis using historical 
GOG-0092 RT arm as control arm by software EAST with accrual and 
drop-out information from GOG-0263. With 24 months of follow-up on 
340 patients, we expected a total of 48 RFS events, which will provide 
77% power to detect a hazard ratio of 0.498 without any compromise to 
the pre-specified study type I error and interim analysis decision rules.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    

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Table 11.1 Projected time for final analysis using historical GOG-0092 RT arm as control arm by 
software EAST with accrual and drop-out information from GOG-0263 
 
Number 
of RFS 
Events 
Power† 
Months 
from 
Accrual 
Suspension 
42 
0.718 
0 
44 
0.735 
0 
45 
0.743 
9 
46 
0.750 
12 
48 
0.767 
20 
50 
0.782 
27 
52 
0.796 
35 
53 
0.803 
40 
 
†: power without adjustment of interim futility analyses is the same as the original study design 
(14-MAR-2022) 
 
11.9 
Planned Minority Inclusion  
The following are the race and ethnicity distribution anticipated for this 
trial based on GOG-0092: 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
55 
+ 
0 
= 
55 
Not Hispanic or Latino 
479 
+ 
0 
= 
479 
Ethnic Category: Total of all subjects 
         534 (A1) +                0  (B1) =                  534   (C1) 
Racial Category 
 
American Indian or Alaskan Native 
2 
+ 
0 
= 
    2 
Asian 
52 
+ 
0 
= 
  52 
Black or African American 
128 
+ 
0 
= 
128 
Native Hawaiian or other Pacific Islander 
3 
+ 
0 
= 
    3 
White 
349 
+ 
0 
= 
349 
Racial Category: Total of all subjects 
          534 (A2) + 
           0  (B2) = 
            534   (C2) 
 
(A1 = A2) 
 
(B1 = B2) 
 
(C1 = C2) 
 
                        Update (11/2017): The following are the race and ethnicity distribution 
anticipated for this trial based on GOG-0092 for a sample size of 360. 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
37 
+ 
0 
= 
37 

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Not Hispanic or Latino 
323 
+ 
0 
= 
323 
Ethnic Category: Total of all subjects 
         360 (A1) +                0  (B1) =                  360   (C1) 
Racial Category 
 
American Indian or Alaskan Native 
1 
+ 
0 
= 
    1 
Asian 
36 
+ 
0 
= 
  36 
Black or African American 
86 
+ 
0 
= 
86 
Native Hawaiian or other Pacific Islander 
2 
+ 
0 
= 
    2 
White 
235 
+ 
0 
= 
360 
Racial Category: Total of all subjects 
          360 (A2) + 
           0  (B2) = 
            360  (C2) 
 
(A1 = A2) 
 
(B1 = B2) 
 
(C1 = C2) 

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12.0 
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International Assessment of Health-Related Quality of Life: Theory, Translation, 
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37.  
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Korea: a validation study of a Korean version of the brief pain inventory. Oncology. 
 
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Havrilesky LJ, Leath CA, Huh W, et al. Radical hysterectomy and pelvic 
 
lymphadenectomy for stage IB2 cervical cancer. Gynecol Oncol. 2004:93:429-
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Eggen T, Arnes M, Moe B, Straume B, Orbo A. Prognosis of early cervical cancer (FIGO 
 
stages IA2, IB, and IIA) in northern Norway predicted by malignancy grading score and 
 
objective morphometric image analysis. Internat J Gynecol Path. 2007:26(4):447-456. 
 
42.   
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44.  
Cantor AB, Shuster JJ. Parametric versus non-parametric methods for estimating cure 
 
rates based on censored survival data. Stat in Med. 1992;11:931-937. 
 
45.  
Cantor A. Extending SAS Survival Analysis Techniques for Medical Research. Vol. 103. 
 
SAS Institute Inc. Cary, NC; 1997. 
 
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Gieser PW, Chang MN, Rao PV, Shuster JJ, Pullen J.  Modelling cure rates using the 
Gompertz model with covariate information. Statistics in Medicine. 1998;17: 831-839. 
 
47.  
Schoenfeld D, Richter JR. Nomograms for calculating the number of patients needed for 
 
a clinical trial with survival as an endpoint. Biometrics. 1982;38:8. 
 
48.   
Cantor AB. Power calculation for the log rank test using historical data. Controlled 
 
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Cantor AB. Sample size calculations for the log rank test: a Gompertz model approach. J 
 
Clin Epidem. 1992;45:1131-1136. 
 
50.  
Begg CB. Ruminations on the intent-to-treat principle. Controlled Clinical Trials. 2000; 
21:241-243. 
 

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51.  
Lachin JM. Statistical considerations in the intent-to-treat principle. Controlled Clinical 
Trials. 2000;21:167-189. 
 
52.  
Sanchez MM, Chen X. Choosing the analysis population in non-inferiority studies: per 
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53.  
Crowley J. A note on some recent likelihoods leading to the log rank test. Biometrika. 
 
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Agresti A. A survey of exact inference for contingency tables. Statistical Science. 1992; 
 
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58.  
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O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 
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Wieand,S,  Schroeder G. Stopping when the experimental regimen does not appear to 
 
help. Stat in Med.1994;13:1453-1458. 
 
 
 

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APPENDIX I 
CARCINOMA OF THE CERVIX UTERI 
FIGO CLASSIFICATION 
2009 
 
 
Stage I 
The carcinoma is strictly confined to the cervix (extension to the corpus 
would be disregarded) 
IA 
Invasive carcinoma which can be diagnosed only by microscopy, with 
deepest invasion ≤ 5mm and largest extension ≥ 7 mm 
IA1               Measured stromal invasion of ≤ 3.0 mm in depth and extension of ≤ 7.0mm 
IA2               Measured stromal invasion of > 3.0 mm and not > 5.0 mm with an      
 extension of not > 7.0 mm 
IB 
Clinically visible lesions limited to the cervix uteri or pre-clinical cancers 
greater than stage IA* 
IB1                Clinically visible lesion ≤ 4.0 cm in greatest dimension 
IB2                Clinically visible lesion > 4.0 cm in greatest dimension 
Stage II 
Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or 
to the lower third of the vagina 
IIA 
Without parametrial invasion 
IIA1              Clinically visible lesion ≤ 4.0 cm in greatest dimension 
IIA2              Clinically visible lesion > 4 cm in greatest dimension 
IIB 
With obvious parametrial invasion 
Stage III 
The tumor extends to the pelvic wall and/or involves lower third of the 
vagina and/or causes hydronephrosis or non-functioning kidney** 
IIIA 
Tumor involves lower third of the vagina, with no extension to the pelvic 
wall 
IIIB 
Extension to the pelvic wall and/or hydronephrosis or non-functioning 
kidney 
Stage IV 
The carcinoma has extended beyond the true pelvis or has involved (biopsy 
proven) the mucosa of the bladder or rectum. A bullous edema, as such, 
does not permit a case to be allotted to Stage IV 
IVA 
Spread of the growth to adjacent organs 
IVB 
Spread to distant organs 
 
*All macroscopically visible lesions—even with superficial invasion—are allotted to stage IB 
carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 
mm and a horizontal extension of not > 7.00 mm. Depth of tissue invasion should not be > 5.00 
mm taken from the base of the epithelium of the original tissue—superficial or glandular. The 
depth of invasion should always be reported in mm, even in those cases with “early (minimal) 
stromal invasion” (~ 1 mm). The involvement of vascular/lymphatic spaces should not change 
the stage allotment. 
**On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. 
All cases with hydronephrosis or non-functioning kidney are included, unless they are known to 
be due to another cause. 

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APPENDIX II (05/12/2014) 
Translational Research Specimen Procedures  
I.  Summary of Specimen Requirements 
 
If the patient gives permission for her specimens to be collected and used for this optional translational research 
component, then participating institutions within the United States are required to submit the patient’s 
translational research specimens as outlined below (unless otherwise specified)..  
Required Specimen 
(Specimen Code) 
Time Point 
Ship To 
FFPE Primary Tumor 
(FP01)* 
1st choice: block 
2nd choice: 16 unstained slides 
(charged, 5µm) 
Prior to all treatment 
GOG Tissue Bank within 8 weeks 
of registration1 
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-0263, 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 
 
Only one GOG Bank ID (# # # # - # # - G # # #) is assigned per patient. All translational 
research specimens and accompanying paperwork must be labeled with this coded and 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 GOG protocols with translational research 
specimen requirements before requesting a GOG Bank ID from the Tissue Bank Portal. Be 
sure to indicate if the patient has a previous GOG# when registering.  This will ensure 
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.  A pre-paid FedEx air bill is provided for the submission of whole blood. 
 
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- # # # #) 

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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). Primary tumor should be collected prior to all treatment. Only 
one block may be submitted per tissue type. 
 
Every attempt should be made to provide a FFPE block; however, if a block cannot be 
provided on a permanent basis, then 16 unstained slides (charged, 5 µm) should be 
submitted. All tissue sections should be cut sequentially from the same block.  
 
Note: 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 or slides) should be specified on Form SP. 
 
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. 
 
 

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VII. 
Submitting Form SP  
 
Form SP must be submitted via SEDES for each required specimen regardless of whether 
the specimen is submitted for research. 
 
A copy of the SEDES-completed Form SP 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 if the specimen is not collected. 
 
Retain a printout of the completed form for your records. 
 
Please contact GOG User Support if you need assistance (Email: support@gogstats.org; 
Phone: 716-845-7767). 
 
VIII. Shipping Translational Research Specimens  
 
A SEDES-completed copy of Form SP must be included for each translational 
research specimen. 
 
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-0263 
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 
 
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. 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, your institution must comply with IATA 
standards (www.iata.org). If you have questions regarding your shipment, contact the 

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GOG Tissue Bank at GOGBank@nationwidechildrens.org or by phoning 866-GOG-
BANC (866-464-2262).  
 
To ship whole blood specimens you will need (1) a sturdy shipping container (e.g., a 
cardboard or styrofoam box), (2) a leak proof biohazard envelope with absorbent 
material*, (3) a puncture and pressure resistant envelope (e.g. Tyvek envelope), (4) an 
Exempt Human Specimen sticker, and (5) a pre-paid FedEx air bill. 
 
*If you will be shipping whole blood specimens from more than one patient, please put 
each specimen in a separate plastic zip-lock bag before placing the specimens in the 
shipping bag. You may include up to four different blood specimens in one biohazard 
envelope. 
 
If you do not have these materials available at your institution, you may order them from 
any supplier (e.g., Saf-T-Pak; Phone: 800-814-7484; Website: www.saftpak.com). 
 
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 SP 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 Translational Research Specimens  
 
The GOG Statistical and Data Center and Tissue Bank (or alternate laboratory) will 
coordinate the distribution of specimens to approved investigators. 
Investigators will not be given access to any personal identifiers. 

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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 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. 
 
X. Banking Translational Research Specimens for Future Research 
 
Specimens will remain in the GOG Tissue Bank and made available for approved research 
projects if the patient has provided permission for the use of her specimens for future health 
research. The patient’s choices will be recorded on the signed informed consent document 
and electronically via the online Specimen Consent 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 distributed prior to revoking consent. 
 
Note: If return of specimens is requested, shipping will be at the institution’s expense. 
 
 
 
 

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APPENDIX III (05/12/2014) 
 
 
RADICAL HYSTERECTOMY AND PELVIC LYMPHADENECTOMY 
 
Purpose 
 
 
1) Surgical cure of carcinoma of the cervix, upper vagina or 
endometrium. 
 
Indications 
 
 
1) Invasive cervical carcinoma clinically confined to the cervix or 
upper vagina. 
2) Invasive vaginal carcinoma clinically confined to the upper vagina. 
3) Endometrial carcinoma extending to the cervix. 
 
Contraindications 
 
1) More advanced stages of disease (surgical or clinical). 
2) Poor surgical risk patient. 
3) Inadequate facilities and/or personnel. 
 
Content of  
Procedure  
A) 
Pelvic Lymphadenectomy 
 
1) 
Bilateral removal of all nodal tissue and skeletonization of all 
vessels from the mid portion of the common iliac artery to the 
circumflex iliac vein; laterally, from the mid portion of the psoas 
muscle to ureter medially including the hypogastric artery and vein 
and from the obturator fossa anterior to the obturator nerve 
 
2) 
Palpably positive nodes should be sampled for histology 
A pathologically positive pelvic or para-aortic node indicates that 
no     further sampling from that area need be performed, unless 
debulking of these nodes is desired. 
     
Unresectable nodes should be marked with clips 
 
B) 
Radical Hysterectomy 
 
1) 
Removal of the uterus and contiguous parametrial tissue to its most 
lateral extent along with para-vaginal tissue and upper 3 of the 
vagina along with the proximal utero-sacral ligaments.  The uterine 
artery should be transected at its origin lateral to the ureter.  The 
ureter must be unroofed from its entry into the broad ligament to 
its intramural portion in the bladder and dissected laterally from its 
attachment to the cardinal ligament 
. 
2)  
May be performed by minimally invasive techniques (laparoscopy, 
robotic) 
 
 
 
 

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ADVERSE EFFECTS THAT MAY BE ASSOCIATED 
 
WITH AN UNEVENTFUL PROCEDURE 
                                                                                                                        
 
SYSTEM 
 
 
      GRADE 
(up to and including) 
                                                                                                                             
 
Hematopoietic  
 
 
 
2 
Genitourinary  
 
 
 
1 
Gastrointestinal 
 
 
 
1 
Hepatic 
 
 
 
 
1 
Pulmonary 
 
 
 
 
1 
Cardiovascular 
 
 
 
1 
Peripheral Neurologic  
 
 
1 
Central Neurologic 
 
 
 
0 
Cutaneous 
 
 
 
 
2 
Lymphatics 
 
 
 
 
1 
Fever 
 
 
 
 
2 
Allergic 
 
 
 
 
0 
                                                                                                                          
 
 
 
 
 
 
 

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APPENDIX IV (05/12/2014)(05/12/2020) 
 
General Chemotherapy Guidelines: 
 
• For 21 or 28 day cycles, a patient will be permitted to have a new cycle of 
chemotherapy delayed up to 7 days (without this being considered to be a 
protocol violation) for major life events (e.g., serious illness in a family member, 
major holiday, vacation which is unable to be re-scheduled).  Documentation to 
justify this decision should be provided. 
 
• It will be acceptable for individual chemotherapy doses to be delivered within a 
“24-hour window before and after the protocol-defined date” for “Day 1” 
treatment of 21 or 28 day cycles.  If the treatment due date is a Friday, and the 
patient cannot be treated on that Friday, then the window for treatment would 
include the Thursday (1 day earlier than due) through the Monday (day 3 past 
due) 
 
• For weekly regimens, it will be acceptable for individual chemotherapy doses to 
be delivered within a “24-hour window,” for example; “Day 8 chemotherapy” can 
be delivered on Day 7, Day 8, or Day 9 and “Day 15 chemotherapy” can be given 
on Day 14, Day 15, or Day 16. 
 
• Chemotherapy doses can be “rounded” according to institutional standards 
without being considered a protocol violation (most institutions use a rule of 
approximately +/- 5% of the calculated dose). 
 
• Chemotherapy doses are required to be recalculated if the patient has a weight 
change of greater than or equal to 10%.  Patients are permitted to have 
chemotherapy doses recalculated for <10% weight changes.  (05/12/2014)