A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients With Pelvic-Only Recurrence of Carcinoma of the Uterine Corpus
Phase: PHASE2
Conditions: Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation, Endometrial Mucinous Adenocarcinoma, Endometrial Squamous Cell Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Serous Adenocarcinoma, Recurrent Endometrial Undifferentiated Carcinoma, Recurrent Uterine Corpus Cancer
Sponsor: GOG Foundation

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 1 - 
PROTOCOL GOG-0238 
A RANDOMIZED TRIAL OF PELVIC IRRADIATION WITH OR WITHOUT CONCURRENT 
WEEKLY CISPLATIN IN PATIENTS WITH PELVIC-ONLY RECURRENCE OF CARCINOMA OF 
THE UTERINE CORPUS 
NCT# 00492778 (04/21/2014) 
NCI Version Date: 05/28/2019 
Includes: Revisions # 1-15 
POINTS: 
PER CAPITA – 20  
MEMBERSHIP – 6 
Lead Organization: NRG / NRG Oncology (04/21/2014) 
 
 
 
 
 
 
 
STUDY CHAIR (10/27/2014) 
 
 
 
STUDY CO-CHAIR (01/18/2011) 
JONATHAN M. FEDDOCK, M.D. 
 
 
JULIAN C. SCHINK, MD  
RADIATION ONCOLOGY OF LEXINGTON 
 
Phone: 833-330-3605 
BAPTIST HEALTH LEXINGTON 
1700 NICHOLASVILLE RD 
 
STUDY CO-CHAIR/RTOG CO-CHAIR (10/18/2010) 
LEXINGTON, KY 40503 
 
PENNY ANDERSON, MD. 
(859) 260-6460  
 
 
 
 
FOX CHASE CANCER CENTER 
FAX: (859) 278-0260 
 
DEPARTMENT OF RADIATION ONCOLOGY 
E-MAIL:jonathan.feddock@bhsi.com 
 
 333 COTTMAN AVENUE 
 
 
 
 
 
 
 
PHILADELPHIA, PA 19111 
NURSE CONTACT  
 
 
 
 
(215) 728-7476 
NANCY MENNING, MSN, ANP-C 
 
FAX: (215) 214-1269 
FRANCISCAN ST. FRANCIS HOSPITAL  
 
EMAIL : p_anderson@fccc.edu 
GYNECOLOGIC ONCOLOGY SPECIALIST 
 
 
 
 
 
 
8111 SOUTH EMERSON AVE., CANCER CTR 
 
STUDY PATHOLOGIST (10/18/2010) 
SUITE 204 
 
 
 
 
 
WILLIAM H. RODGERS, Ph.D., M.D. 
INDIANAPOLIS, IN 43237 
 
56-45 MAIN ST 
PHONE: (317) 528-2566  
 
 
 
FLUSHING, NY 11355-4562  
FAX: (317) 528-1336 
 
 
 
 
EMAIL: whr9001@nyp.org   
E-MAIL: nancy.menning@franciscanalliance.org 
 
 
STATISTICIAN  
 
 
 
 
DANIELLE ENSERRO, PHD. 
 
EMAIL: enserrod@nrgoncology.org 
 
 
 
 
 
 
 
 
IROC Houston (formerly the RADIOLOGICAL PHYSICS CENTER (RPC) CONTACT (01/18/2011) (04/21/2014)  
 
JESSICA R. LOWENSTEIN, MS., DABR  
  
 
 
  
 
 
  
 
 
 
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 (04/21/2014) 
 
ALLIANCE / Alliance for Clinical Trials in Oncology 
ECOG-ACRIN / ECOG-ACRIN Cancer Research Group 
SWOG / SWOG 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 2 - 
 
PROTOCOL GOG-0238 
A RANDOMIZED TRIAL OF PELVIC IRRADIATION WITH OR WITHOUT CONCURRENT 
WEEKLY CISPLATIN IN PATIENTS WITH PELVIC-ONLY RECURRENCE OF CARCINOMA OF 
THE UTERINE CORPUS  
NCI Version Date: 05/28/2019 
Includes: Amendments # 1-15 
POINTS: 
PER CAPITA – 20 
MEMBERSHIP – 6 
 
CONTACT INFORMATION (04/21/2014) 
To submit site registration 
documents: 
For patient enrollments: 
Submit study data 
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. 
Please refer to the patient 
enrollment section of the protocol 
for instructions on using the 
Oncology Patient Enrollment 
Network (OPEN) which can be 
accessed at 
https://www.ctsu.org/OPEN_SYS
TEM/ or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk 
with any OPEN-related questions 
at 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 on with 
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 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 3 - 
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.  
 
The CTSU Website is located at https://www.ctsu.org. 
 
 
OPEN TO PATIENT ENTRY FEBRUARY 25, 2008; REVISED OCTOBER 8, 2008 
REVISED FEBRUARY 8, 2010; REVISED OCTOBER 18, 2010; REVISED MAY 23, 2011; 
REVISED MAY 14, 2012; REVISED JUNE 18, 2012; REVISED APRIL 21, 2014; REVISED OCTOBER 27, 2014; 
REVISED May 28, 2019. 
 
 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 4 - 
 
SCHEMA 
 
Institutional IMRT Credentialing is required before registering any patient on this trial. 
Knowledge Assessment must be completed by the treating radiation oncologist. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Patients with tumors involving the distal vagina with clinically negative groins, the bilateral inguino-
femoral lymph node regions should be treated to 4500 cGy.  
3-D conformal or IMRT boost is allowed for patients who are not candidates for brachytherapy.  
 
 
 
  
 
 
Recurrent carcinoma of the uterine corpus 
confined to the pelvis/vagina 
 
GOG-238 Consent/Enrollment 
RANDOMIZATION 
REGIMEN I 
 
Whole Pelvis Radiation 
4500 cGy in 25 fractions to the 
whole pelvis  
(180 cGy/fraction)  
+ Interstitial or Intracavitary 
Brachytherapy or external beam 
boost 
 
REGIMEN II 
 
Whole Pelvis Radiation 
4500 cGy in 25 fractions to the 
whole pelvis  
(180 cGy/fraction) 
+ Weekly Cisplatin (40 mg/m2/wk) 
+ Interstitial or Intracavitary 
Brachytherapy or external beam 
boost 

 
- 5 - 
 
 
TABLE OF CONTENTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                    PAGE 
 
1.0 
OBJECTIVES ............................................................................................................ - 7 - 
1.1 
Primary Objectives .......................................................................................... - 7 - 
1.2 
Secondary Objectives ...................................................................................... - 7 - 
2.0 
BACKGROUND AND RATIONALE........................................................................ - 7 - 
2.1 
Inclusion of Women and Minorities ................................................................ -10-  
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS ....................................................... - 11 - 
3.1 
Eligible Patients ............................................................................................ - 11 - 
3.2 
Ineligible Patients.......................................................................................... - 12 - 
4.0 
STUDY MODALITIES ............................................................................................ - 14 - 
4.1 
Cisplatin (Cis-diamminedichloroplatinum, Platinol) ...................................... - 14 - 
4.2 
Radiation Therapy (05/14/2012) .................................................................... - 15 - 
5.0 
TREATMENT PLAN AND ENTRY........................................................................ - 31 - 
5.1 
Before any patient is enrolled on this study the treating radiation oncologist must 
complete a Knowledge Assessment Questionnaire found on the IROC Houston website. 
(10/8/2008) (04/21/2014) .......................................................................................... - 31 - 
5.2 
Registration Procedures (04/21/2014) ........................................................... - 33 - 
5.3 
Patient Entry and Registration (04/21/2014) .................................................. - 35 - 
5.4 
Randomization and Treatment Plan ............................................................... - 36 - 
5.5 
Criteria for removal from treatment ............................................................... - 38 - 
6.0 
TREATMENT MODIFICATIONS .......................................................................... - 39 - 
6.1 
Hematologic Adverse Effects ........................................................................ - 39 - 
6.2 
Gastrointestinal Adverse Effects ................................................................... - 40 - 
6.3 
Renal/Genitourinary Adverse Effects ............................................................ - 42 - 
6.4 
Cutaneous Adverse Effects............................................................................ - 43 - 
6.5 
Treatment of Hypersensitivity Reactions to Cisplatin: ................................... - 43 - 
6.6 
Radiotherapy Treatment Method Modifications (10/8/2008) ......................... - 44 - 
7.0 
STUDY PARAMETERS .......................................................................................... - 45 - 
7.1 
Observations and Tests ................................................................................. - 45 - 
7.2 
PATHOLOGY REQUIREMENTS (10/18/2010) .......................................... - 46 - 
7.3 
TRANSLATIONAL RESEARCH (10/18/2010) ........................................... - 46 - 
7.4 
QUALITY OF LIFE ASSESSMENTS (10/18/2010) ..................................... - 46 - 
8.0 
EVALUATION CRITERIA ..................................................................................... - 47 - 
8.1 
Parameters of Outcome – GOG RECIST Criteria .......................................... - 47 - 
9.0 
DURATION OF STUDY ......................................................................................... - 49 - 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES................................. - 50 - 
10.1 
ADVERSE EVENT REPORTING FOR A COMMERCIAL AGENT 
(04/21/2014) ............................................................................................................. - 50 - 
10.2 
GOG DATA MANAGEMENT FORMS (10/18/2010) .................................. - 53 - 
11.0 
STATISTICAL CONSIDERATIONS ...................................................................... - 56 - 
11.1 
Study design overview and registration: ........................................................ - 56 - 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 6 - 
11.2 
Data collection: ............................................................................................. - 56 - 
11.3 
Accrual: ........................................................................................................ - 57 - 
11.4 
Hypotheses and sample size: ......................................................................... - 57 - 
11.5 
Study Duration: ............................................................................................ - 59 - 
11.6 
Interim Analyses: .......................................................................................... - 60 - 
11.7 
Anticipated Gender and Minority Inclusion: ................................................. - 60 - 
12.0 
BIBLIOGRAPHY .................................................................................................... - 61 - 
APPENDIX I ....................................................................................................................... - 64 - 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 7 - 
1.0 
OBJECTIVES 
 
1.1 
Primary Objectives 
 
1.11 
To assess whether pelvic radiation therapy with concurrent cisplatin is 
more promising with respect to progression-free survival than pelvic 
radiation therapy alone in the treatment of recurrent uterine carcinoma 
limited to the pelvis and vagina. 
 
1.2 
Secondary Objectives 
 
1.21 
To capture the sites of recurrence subsequent to treatment with pelvic 
radiation with or without concurrent weekly cisplatin in women with 
recurrent uterine carcinoma. 
 
1.22 
To estimate overall survival of patients with recurrent uterine carcinoma 
treated  with pelvic radiation therapy with or without concurrent weekly 
cisplatin.  
 
1.23 
To estimate the prognostic significance of the location (central pelvis 
versus vagina) and size of the recurrence in addition to the prognostic 
significance in the salvage setting of the histological subtype, grade, 
patient age, race, performance status, and the presence of lymph-vascular 
space involvement of  the original tumor at the time of  initial 
hysterectomy 
 
 
 
1.24 
To evaluate toxicity derived from the combined cisplatin and radiation  
 
 
 
compared with radiation alone in this patient population.  
 
2.0 
BACKGROUND AND RATIONALE 
 
Endometrial cancer (EC) is the most common gynecologic malignancy.  An estimated 
41,200 new cases of EC are expected to be diagnosed in 2006.1  After increasing from 
1988 to 1998, incidence rates of EC leveled off through 2001.  An estimated 7,350 deaths 
from uterine corpus cancer are expected in 2006.1  The majority of these patients present 
with early stage disease, with survival rate over 80% after primary surgery.  
Unfortunately, most patients with advanced EC generally die from progression of their 
disease.  
 
Two recently published large randomized trials, GOG-00992 and PORTEC,3 evaluated 
the role of adjuvant pelvic radiation therapy (RT) in patients with early stage EC, 
endometrioid histologies, after surgery with or without complete surgical staging.  In both 
trials, the pelvis alone (including regional-nodal, pelvic and vagina) was the most 
common site of initial failure in non-irradiated patients (8.9% in GOG-0099 and 14% in 
the PORTEC trial).  In these two trials and others 4 adjuvant pelvic RT is associated with 
an improvement in loco-regional control, but does not statistically significantly impact 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 8 - 
the overall survival or distant failure rate within the entire study population.  The most 
common site of pelvic recurrence is the vagina, accounting for almost two thirds of the 
pelvic recurrences in the GOG-00992 and PORTEC3  trials.  Neither one of these trials, 
however, were powered to show a difference in survival in their low and/or intermediate 
risk patient populations which have competing risks of death.  In both trials, adjuvant RT 
was associated with increased treatment-related morbidity.  The lack of impact of pelvic 
RT on overall survival has led to many centers to abandon adjuvant radiation in patients 
with intermediate risk EC.  A commonly espoused justification for abandoning adjuvant 
radiotherapy in the intermediate risk group is the belief that most women with isolated 
pelvic recurrence will be cured with salvage therapy.  Unfortunately, prospective clinical 
trial data establishing the success rate for this salvage therapy is limited.   
 
In GOG-0122, a Phase III randomized trial comparing “Whole Abdominal Radiotherapy 
(WAR) versus Combination Doxorubicin-Cisplatin (AP) Chemotherapy in Advanced 
Endometrial Carcinoma”5 chemotherapy significantly improves progression-free survival 
(PFS) and overall survival when compared with WAR.  Although the risk of death was 
reduced by 32% in the chemotherapy arm, 18% of these patients experienced an isolated 
vaginal or pelvic recurrence5 as their initial site of recurrence.  
 
STUDY 
GOG #0099  
(NFT vs. RT) 
PORTEC 
(NFT vs. RT) 
GOG # 0122 
(WAR vs. AP) 
Site of Failure 
 
 
 
Vagina 
7.6% vs. 1.1% 
10.2% vs. 2.3 % 
5% vs. 5.7% 
Pelvis 
3.0% vs. 0.5% 
3.4% vs. 2.0 % 
8.4% vs. 12.3% 
Distant 
6.4% vs. 5.3% 
7.0% vs. 7.9% 
22% vs. 18% 
NFT: No further therapy; RT: Radiation therapy; WAR: Whole abdominal radiotherapy; 
AP: Adriamycin + Platinum chemotherapy 
 
The rates of pelvic recurrence in patients with early stage disease after surgery alone 
range between 5-15%, most of which are isolated vaginal recurrences.  The reported 
salvage rate with radical irradiation is 65-80% in patients with isolated vaginal relapses.6, 
7  The results are less favorable in patients with pelvic and/or regional recurrences (<50% 
salvage rate).6, 7  Ackerman et al6 performed a retrospective analysis of 54 patients with 
vaginal recurrence of their endometrial cancer identifying patterns of relapse, 
determining the outcome of salvage treatment and examining the factors predictive of 
effective salvage.  Initial therapy was surgery alone in 32 patients and surgery plus 
adjuvant pelvic irradiation (RT) in 22 patients.  Isolated pelvic recurrences occurred in 
72% of patients who underwent surgery alone and 23% of patients who received adjuvant 
RT in addition to surgery.  Twenty-eight of the 54 patients in her study had isolated 
pelvis only recurrence.  Sixteen of 28 patients with pelvic relapses recurred in the vagina 
only.  With a minimum follow-up of 5 years, 67% had pelvic control until death (79% of 
patients with vaginal recurrences and 43% of patients with pelvic recurrences), after 
definitive RT. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 9 - 
Updated treatment and salvage therapy results of the PORTEC trial were published by 
Creutzberg et al in 20037 with 8-year local control and survival rates after relapse in 
patients with pathological stage I endometrial cancer.  With a median follow-up of 73 
months, 8-year actuarial locoregional recurrence (LRR) rates were 4% (13 patients) and 
15% (46 patients) in the adjuvant RT and control groups, respectively (p<0.0001).  
Again, there was no difference in the actuarial overall survival rates (71% and 77%, 
respectively) or distant metastasis rates (10% and 6%, respectively) between the two 
groups.  The majority of the locoregional recurrences in the control group were in the 
vagina (32/46 patients).  Subsequent subset analysis indicated that patients with grade 1-2 
disease with < 50% myometrial infiltration and patients less than 60 years old, had a LRR 
rate of <5%.  However, patients with deep myometrial invasion (> 50%) and patients 
with grade 3 disease had a LRR between 7-15%.  As expected, adjuvant RT eliminates 
the risk of LRR after surgery. 
 
It has been postulated by many that the lack of survival benefit of adjuvant RT is due to 
the high rate of successful salvage after relapse, primarily in patients with isolated 
vaginal relapses, and the increased incidence of distant failures.  However, it is important 
to recognize that in Creutzberg’s series, of the 46 (13%) LRR in the control group only 
22 were salvaged and remained without evidence of disease at the time of the last follow 
up (48%).  Furthermore, evaluation of the patients who died from endometrial cancer due 
to LRR alone, demonstrates an incidence of 10% (3/29) in the RT group vs. 25% (6/24) 
in the control group.  The actuarial survival after first relapse is lower for the RT group 
when compared with the control group (3-year survival of 19% and 51% for each group, 
respectively, p=0.004), however, this type of comparison can be considered biased as it 
selects out of the RT arm nearly all local recurrences due to the effectiveness of RT on 
local control.  In addition, Creutzberg et al.7 have shown significantly better 3-year 
survival rates after vaginal recurrence alone when compared with pelvic or distant relapse 
(73%, 8%, and 14%, respectively, p<0.01).  Furthermore, the survival after vaginal 
relapse was significantly better for patients in the control group compared with women 
who received adjuvant RT (65% vs. 43%, respectively).  Of course, this is an expected 
finding since the former group was able to receive full doses of salvage RT while the 
latter group would have dose limitations due to prior pelvic RT.  
 
Phase II chemotherapy trials in women with advanced or recurrent endometrial cancer 
have identified doxorubicin, cisplatin, carboplatin, and paclitaxel 8-16 as active agents 
with response rates of 30-35%.  In addition, there is extensive clinical experience 
combining cisplatin with external beam irradiation in cervical cancer.  A number of large 
randomized studies evaluating concurrent platinum-based chemoradiotherapy treatment 
in cervical cancer have shown superior rates of loco-regional control, disease-free 
survival, and overall survival when compared with RT alone.17-20  Further support for the 
use of concurrent cisplatin and radiation in the treatment of endometrial cancer comes 
from two GOG studies.  A Phase I study of weekly cisplatin and whole abdomen 
radiation (WAR) for the treatment of stage III and IV endometrial cancer reported by 
Reisinger et al21 found that this regimen was well-tolerated acutely, and late toxicity was 
similar to that seen with WAR alone.  The rationale for the use of cisplatin in conjunction 
with radiation in this setting included the radiation-sensitizing properties of cisplatin, the 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 10 - 
cytotoxic activity of cisplatin in endometrial cancer, and the relatively limited bone 
marrow toxicity of cisplatin compared with other agents active in EC.  While too few 
patients were treated to make definitive conclusions, it is interesting to note that no 
isolated recurrences were seen in the radiation treatment field following this regimen.21  
A subsequent study reported by Soper et al22 treated patients with the same chemotherapy 
regimen followed by four cycles of subsequent doxorubicin and cisplatin every three 
weeks in an attempt to control systemic disease.  Patients again tolerated the WAR and 
concurrent cisplatin confirming the tolerability reported for the GOG study by Reisinger, 
et al. 
 
The only prospective clinical trial data documenting the salvage rate of radiotherapy in 
women with endometrial cancer is from the PORTEC7 study.  With an actuarial survival 
of only 51% at three years for the 46 women with pelvic recurrence of endometrial 
cancer without prior radiotherapy, it is imperative that we develop better strategies for 
managing these patients.  Several retrospective series have shown that the prognosis of 
patients with regional recurrences from endometrial cancer is very poor, with low salvage 
rates with RT alone, and high risk for distant failures.6, 23-29  
 
The adoption of chemo-radiation using the well-established regimen of weekly cisplatin 
is the most logical first step.  As adjuvant chemotherapy is increasingly prescribed 
instead of adjuvant radiotherapy for women with endometrial cancer the likelihood of 
developing pelvic recurrence is increased.  Mundt et al30 found a 39.5% rate of pelvic 
recurrences in 43 patients with high-risk pathological stage I-IV endometrial cancer after 
adjuvant chemotherapy alone without pelvic RT.  
 
We have designed a randomized Phase II screening study to estimate the relative benefit 
on progression-free survival of the addition of cisplatin to external pelvic irradiation, 
estimate overall survival and toxicity, and evaluate clinical, host and pathologic factors at 
study entry and from the original hysterectomy as potential prognostic factors.  
 
2.1 
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 endometrial cancer 
population with recurrent disease limited to the pelvis treated by participating 
institutions.  
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 11 - 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS 
 
3.1 
Eligible Patients   
 
3.11 
All patients must have undergone complete hysterectomy and bilateral 
salpingo-oophorectomy at the time of the original therapy for their uterine 
carcinoma. 
 
3.12 
Patients must have a biopsy with histologically confirmed diagnosis of 
recurrent endometrial cancer confined to the pelvis and/or vagina and no 
evidence of extrapelvic disease.  
 
3.13 
Patients must have endometrial carcinoma including endometrioid 
adenocarcinoma, adenocarcinoma with squamous differentiation, 
mucinous adenocarcinoma, squamous cell carcinoma, mixed carcinoma, 
undifferentiated carcinoma, clear cell adenocarcinoma, and serous 
adenocarcinoma histologies.  
 
 
3.14 
Patients must have no evidence of extrapelvic disease. Complete workup 
staging should be performed prior to initiation of therapy to rule-out 
presence of metastatic disease. This should include: CT scan of the thorax 
with IV contrast, as well as a CT of the pelvis and abdomen with IV and 
PO contrast performed using multi-detector CT and equal or less than 5 
mm slice thickness.  If the patient is unable to tolerate contrast, then MRI 
with IV gadolinium should be performed. A chest x-ray should be done 
first, and if abnormal, then a CT scan of the chest should be done.  
(10/8/08) 
 
 
 
3.15 
Primary surgical debulking before protocol therapy is permissible. This 
would include removal of gross symptomatic disease in the pelvis and/or 
vagina.  
 
Exenterative surgery is not permissible. Patients enrolled subsequent to 
revision 11 with complete resection of gross recurrent disease are eligible. 
(05/14/2012) 
   
3.16 
Patients may have received prior hormone therapy and/or systemic 
chemotherapy.  Such therapy must have been completed at least 6 months 
prior to study entry and the patient has clear evidence of disease 
subsequent to such therapy. Patients must not have received neoadjuvant 
chemotherapy for the present recurrent disease. 
 
3.17 
Patients must have GOG performance status 0, 1, or 2. 
 
3.18 
Patients must have an estimated survival greater than or equal to 3 months 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 12 - 
3.19 
Patients must have adequate: 
 
3.191 Bone Marrow Function:  Absolute neutrophil count (ANC)  
1,500/mm3, equivalent to Common Toxicity Criteria (CTCAE v 
3.0) grade 1. Platelets  100,000/mm3 (CTCAE v3.0 grade 0-1). 
 
3.192 Renal Function: Creatinine  institutional upper limit normal 
(ULN), CTCAE v 3.0 grade 0.  Note:  If creatinine > ULN, 
creatinine clearance must be >50 mL/min. 
 
3.193 Hepatic Function: Bilirubin  1.5 x ULN (CTCAE v3.0 grade 1).  
SGOT  and alkaline phosphatase  2.5 x ULN (CTCAE v3.0 grade 
0-1). 
 
3.194 Neurologic Function: Neuropathy (sensory and motor)  CTCAE 
v3.0 grade 1. 
 
3.110 Patients with ureteral obstruction must undergo stent or nephrostomy tube 
 
placement prior to study entry. 
 
3.111 Patients who have met the pre-entry requirements specified in Section 7.0. 
 
3.112 Patients must have signed an approved informed consent and HIPAA 
authorization. 
 
3.2 
Ineligible Patients 
 
3.21 
Patients with evidence of disease outside of the pelvis, including presence 
of positive periaortic or inguino-femoral nodes.  
 
3.22 
Patients who have received previous vaginal, pelvic, or abdominal 
irradiation.    
 
3.23 
Patients who received chemotherapy directed at the present recurrence. 
 
3.24 
Patients with septicemia or severe infection. 
 
3.25 
Patients who have circumstances that will not permit completion of this 
study or the required follow-up. 
 
3.26 
Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, 
or renal transplantation, that would require modification of radiation 
fields. 
 
3.27 
Patients with a history of other invasive malignancies, with the exception 
of non-melanoma skin cancer, are excluded if there is any evidence of 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 13 - 
other malignancy being present within the last five years.  Patients are also 
excluded if their previous cancer treatment contraindicates this protocol 
therapy. 
 
3.28 
Patients enrolled prior to revision 11 who have undergone complete 
surgical resection of the recurrent tumor and have no evidence of residual 
disease evaluable clinically and by CT or MRI imaging, following 
resection. (05/14/2012) 
  
3.29 
Patients who have a significant history of cardiac disease, i.e., 
uncontrolled hypertension, unstable angina, congestive heart failure, or 
uncontrolled arrhythmias within 6 months of registration. 
 
3.210 Patients with history of active collagen vascular disease. 
 
3.211 Patients with GOG Performance Grade of 3 or 4. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 14 - 
4.0 
STUDY MODALITIES  
 
4.1 
Cisplatin (Cis-diamminedichloroplatinum, Platinol) 
 
4.11 
Formulation: Cisplatin is available in aqueous solution in 50 mg and 100 
mg vials with 9 mg/mL of sodium chloride. 
 
4.12 
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. 
 
4.13 
Storage: The aqueous solution should be stored at room temperature and 
 
protected from light.  
 
4.14 
Adverse effects:  
 
4.141 Frequent: Leukopenia, thrombocytopenia, anemia, nausea, 
vomiting, nephrotoxicity, ototoxicity, peripheral neuropathy, 
electrolyte imbalance, hypocalcemia, hypomagnesemia, 
aminoglycoside ototoxicity, ocular toxicity, and allergic reactions.  
 
4.142 Infrequent: Cardiac abnormalities, anorexia, elevated SGOT, rash, 
alopecia, and acute myeloid leukemia. 
 
4.143 NOTE: Aminoglycoside antibiotics given before, with, or after 
cisplatin may potentiate renal toxicity and should be avoided 
whenever possible. 
 
4.144 Severe renal toxicity can be largely avoided by induction of a 
diuresis before, during, and after treatment.  
 
4.145 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. 
 
4.146 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. 
 
4.147 Allergic reactions are rare.  If accompanied by respiratory 
symptoms, allergic reactions require discontinuation of treatment.  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 15 - 
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. 
 
4.148 Local necrosis and thrombophlebitis can be avoided by careful 
 
administration. 
 
4.149 Neurotoxicity may be related to cumulative dose and severe 
toxicity can be largely avoided by careful monitoring for evidence 
of paresthesias and timely discontinuation of treatment.  Ataxia has 
been described. 
 
4.150 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.  
 
4.15 
Drug Interactions 
 
Phenytoin: cisplatin decreases the effect of phenytoin 
 
Aminoglycosides, amphotericin B; increased renal toxicity 
 
Loop Diuretics (furosemide): increased risk of ototoxicity 
 
 
4.16 
Supplier: Commercially available. 
 
4.17 
Administration: See Section 5.44 (10/8/08) 
 
 
 
Refer to package insert for additional information. 
 
4.2 
Radiation Therapy (05/14/2012) 
 
4.21 
Patients will receive a random treatment assignment of either pelvic 
radiation therapy daily Monday-Friday for approximately 5 weeks 
followed by brachytherapy, or the same external beam irradiation to the 
pelvis in combination with intravenous cisplatin given on a weekly basis x 
5 weeks, to be followed by brachytherapy.  When brachytherapy is not to 
be used, a three dimensional treatment or intensity modulated radiotherapy 
(IMRT) boost is allowed. IMRT credentialing is required (see Section 
5.0). All the external beam irradiation must be completed within 6 weeks 
of its initiation. Brachytherapy should be completed within 4 weeks of 
completion of external beam irradiation.  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 16 - 
 
IMRT will be allowed for the entire course of therapy, this is for the 
treatment of the whole pelvis and/or the boost in those cases not 
undergoing brachytherapy. 
 
If IMRT is to be used, treatment plans for such patients must be 
electronically submitted for a rapid review PRIOR TO DELIVERING 
ANY PROTOCOL TREATMENT.  Before ANY patient is enrolled on 
this study the treating radiation oncologist must complete a Knowledge 
Assessment Questionnaire found on the IROC Houston (formerly the 
Radiological Physics Center [RPC]) website 
(http://irochouston.mdanderson.org). (10/8/2008) (04/21/2014) 
 
All IMRT plans need to be submitted for a rapid review prior to delivering 
any protocol treatment for the first patient treated at any particular 
institution  
 
4.211 The investigators will submit a brief radiation treatment plan for 
each patient at time of study entry, to ensure that sites do not 
modify their radiation plan if the patient is randomized to 
chemoradiation.  This brief summary of the planned radiation must 
include a description of the external beam radiation fields and 
dose, as well as the plan for brachytherapy boost (intracavitary 
and/or interstitial).  When brachytherapy is not to be used, a three 
dimensional treatment or intensity modulated radiotherapy (IMRT) 
boost is allowed and plans for such therapy must be submitted, as 
well. (10/8/2008) 
 
4.212 Institutions that are considering administering an IMRT MUST be 
credentialed by IROC Houston. Instructions for credentialing are 
available at the IROC Houston website, 
http://irochouston.mdanderson.org (see Section 5.0 for details). 
(10/8/2008) (05/14/2012) (04/21/2014) 
 
4.2121 When IMRT is to be used each institution must submit and 
successfully complete a protocol-specific plan for the first 
patient treated at that institution on this protocol. A rapid 
review will be performed PRIOR TO DELIVERING ANY 
PROTOCOL TREATMENT. The rapid review will be 
conducted by IROC Houston and suggestions regarding 
protocol compliance will be forwarded from IROC 
Houston to the radiation oncologist at the participating 
institution. IMRT treatment plans for subsequent patients 
enrolled at a particular site will not be required to go 
through the rapid review process via IROC Houston prior 
to treatment, but a review of the treatment plan for each 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 17 - 
patient will be performed by the GOG for each patient. For 
instructions on the rapid review process, please see section 
4.21112. (10/8/2008) (04/21/2014) 
 
4.2122 Institutions may NOT submit a plan for 3D conformal 
treatment and then switch to IMRT treatment during the 
course of the study. (10/8/2008) 
 
Each institution is to determine if IMRT for the pelvis +/- 
boost is to be used at the time of the randomization. This 
remains the same except that it would refer to the entire 
IMRT plan rather than just the boost. (05/14/2012) 
 
4.22 
Physical Factors 
 
4.221 External beam radiation will be delivered using a linear accelerator 
with a nominal photon beam energy of 6 MV or greater.  SAD of 
100 cm is required unless the Tomotherapy device is used.  
Institutions using IMRT must use megavoltage equipment capable 
of delivering static IMRT with a multileaf collimator or dynamic 
IMRT using either an MLC or tomotherapy.  Forward or inverse 
treatment planning methods are acceptable. 
 
4.222 Intracavitary Low dose rate (LDR) and High dose rate (HDR) 
intracavitary brachytherapy alone, in combination with external 
beam irradiation, is allowed only in patients with minimal vaginal 
disease limited to the mucosa or for lesions with an estimated 
thickness less or equal than 5 mm.  Interstitial LDR or HDR 
brachytherapy is required for patients with isolated vaginal 
recurrences with an estimated thickness over 5 mm. 
 
 
4.23 
Localization and Simulation:  
 
4.231 Primary to simulation it is recommended that radiopaque marker 
seeds are inserted into the vaginal apex or at the edges of the gross 
disease as delineated by pelvic exam, to help to identify the area by 
CT scan. Patients are to be immobilized in the supine position in 
an immobilization device such as Vac-lok or alpha-cradle, with 
fixation of the upper body, trunk and proximal thighs. Patients are 
to be treated in the immobilization device. CT scan thickness 
should be 3 mm or smaller through the region that contains the 
PTV, extending from L1-2 level to below the perineum. Care 
should be taken to scan the entire volume of both kidneys during 
the CT simulation for patients undergoing IMRT.  
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 18 - 
 
Patients can be immobilized in the Belly Board in prone position 
with full bladder as per Institutional guidelines. (05/14/2012) 
 
4.232 CT simulation is required to define gross tumor volume (GTV), 
clinical target volume (CTV) and planning target volume (PTV). 
The CT scan should be acquired in the same position and 
immobilization device as for treatment. The use of IV contrast and 
2 hours bowel prep-contrast, are highly recommended for better 
delineation of the contrast enhanced pelvic vessels used as a 
surrogate for regional nodal delineation, as well as small bowel 
contouring, respectively.   
 
4.2321 Planning of the external beam (3DRT or IMRT) should be 
done with a full bladder scan 
 
4.233 Contouring the Target volumes: 
 
4.2331 Please refer to the RTOG Gynecological Atlas for volume 
specification. The atlas may be accessed on the RTOG 
website at: 
http://www.rtog.org/CoreLab/ContouringAtlases/GYN.asp
x 
 
4.2332 The primary gross tumor volume in the vagina and/or 
pelvis should be contoured as gross tumor volume (GTVp).  
This is defined as all gross disease based on clinical pelvic 
examination as well as CT and/or MRI findings. Any gross 
lymph node disease should be as well contoured 
independently as regional-gross tumor volume (GTVr). 
 
4.2333 The clinical target volume (CTV1) is defined as the GTV in 
the vagina +/- pelvis plus the areas considered to contain 
potential microscopic disease. The primary CTV or CTV2 
should include the GTV with 2 cm cranio-caudal and 1.5 
cm axial margins. A minimum of 3 cm of normal vagina 
should be contoured distally to the gross disease in patients 
with vaginal recurrences. The distal margin of the external 
beam radiation fields (based on the CTV1) should be 
confirmed clinically as well as per CT using the most-distal 
seed marker placed in the vagina as a surrogate. The most 
inferior aspect of the external beam radiation field should 
be at least 1cm inferior to the obturator foramen, whatever 
margin is the most inferior one.  The nodal CTV, included 
in the CTV1, should include the internal (hypogastric and 
obturator), external and common iliac lymph node regions. 
The CTV1 should be delineated using the contrast-

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 19 - 
enhanced (preferably IV contrast administered) iliac 
vessels, in addition to the perinodal soft tissue (minimum of 
7 mm axial margin around the vessels). On the pelvic wall 
side the margin will exclude the psoas and the piriformis 
muscles. Bone and intraperitoneal small bowel should be 
excluded from the CTV as much as possible (leaving at 
least 5 mm margin around the vessels) and providing 
adequate margin around GTV is obtained (margin can be 
reduced in the axial margin to 1 cm around the GTV, when 
in close proximity to small bowel).  
 
Approximately 1-2 cm of tissue anterior to the sacrum (S1-
S3) is usually added to the CTV1 for adequate coverage of 
presacral nodes. In addition, the most antero-lateral margin 
of the external iliac nodes that lie just proximal to the 
inguinal canal should be excluded from the CTV1 (nodal 
CTV should stop at the femoral head. Proximately, the 
CTV1 should end 7 mm from the L4-5 interspace to 
account for the PTV1.  
 
 
4.2334 The PVT1 should provide a 7 mm margin in all directions 
around the CTV1. The PTV2 volume to be treated using 
3D conformal techniques or IMRT in patients that are not 
candidate for brachytherapy boost should encompass the 
CTV2 as defined above with a 7 mm margin in all 
directions.  
 
 
4.2335 The definitions of volumes will be in accordance with the 
1993 ICRU report #50. Prescribing, recording and 
reporting photon beam therapy and 1999 ICRU report #62.  
 
 
4.2336 Critical normal surrounding structures:  
 
4.23361 Bladder will be contoured in each slice including 
the portion inferior to the PTV. 
 
4.23362 Rectum will be contoured in each slice including 
the portion inferior to the PTV and superiorly to 
the level that leaves the posterior pelvis around 
the region of the recto-sigmoid colon. 
 
4.23363 Small bowel will be contoured in each slice 
including at least 2cm above the PTV. 
 
4.23364 Femoral heads and the sacrum will be contoured 
in all the slices. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 20 - 
 
4.23365 Kidneys should be contoured in all IMRT cases. 
 
 
 
4.234 Constraints: participants are strongly encouraged to respect the 
following limits, including the 3D conformal or IMRT boost. 
(05/14/2012) 
 
 
4.2341 Small bowel: <30% to receive ≥ 40Gy, minor deviation  
 
30% to 40Gy. 
 
 
4.2342 Rectum: < 60% to receive ≥ 55Gy, minor deviation 40% to 
62Gy. (02/08/10) 
 
 
4.2343 Bladder: < 60% to receive ≥ 55Gy, minor deviation 50% to 
50Gy. 
 
 
4.2344 Femoral heads: < 50% to receive ≥ 40Gy, minor deviation 
50% to 50Gy. The maximum delivered dose to point is 
54Gy. (02/08/10) 
 
 
 
 
4.2345 Iliac crests: <50% to receive ≥30 Gy 
 
 
4.2346 Unspecified tissue (tissue contained within the skin or any 
other normal structure not delineated above and outside the 
PTV, not included within any other structure): No more 
than 1% or 1cc (whichever is smaller) of the tissue outside 
the PTV will receive > 110% of the dose prescribed to the 
PTV.  
 
4.2347 Kidneys: < 33% to receive ≥ 15 Gy, minor deviation 33% 
receiving 15 Gy. 
  
4.24 
Treatment Plan, Dose Specification and Distribution 
 
4.241 The volume irradiated with the whole pelvic fields will include the 
totality of the gross disease locally and regionally, as visualized by 
CT scan, the CTV and PTV as defined above. 
 
4.242 The whole pelvis will receive a total dose of 4500 cGy in 25 
fractions at 180 cGy/fx, encompassing the PTV, using a four-field 
technique throughout the entire treatment.  The prescription dose is 
the isodose that encompassed at least 97% of the PTV. No more 
than 20% of any PTV should receive >110% of the prescribed 
dose. No more than 1% of the PTV should receive <93% of the 
prescribed dose. No more than 1% or 1cc (whichever is smaller) of 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 21 - 
the tissue outside the PTV will receive >110% of the dose 
prescribed to the PTV. 
 
4.243 In patients with tumors involving the distal vagina with clinically 
negative groins, the bilateral inguino-femoral lymph node regions 
should be treated to 4500 cGy.  Planning CT is recommended to 
adequately determine the depth of the inguino-femoral nodes.  A 
number of techniques have been used to treat the areas at risk 
without over-treating the femoral necks.  Some of the most 
commonly used techniques include the use of unequal loading (2:1, 
AP/PA), a combination of low and high energy photons (6MV, 
AP, and 15-18 MV, PA), or equally weighted beams with a 
transmission block in the central AP field, utilizing small AP 
photon or electron beams to deliver a daily boost to the inguino-
femoral nodes.  A technique has been developed and implemented 
at Indiana University, which uses a narrow PA field to treat the 
pelvis, and a wider AP field encompassing the pelvis and inguino-
femoral nodes, with daily AP photon boost to the inguinal nodes 
being delivered using the asymmetric collimator jaws.31 
 
4.244 Patients with pelvic recurrence not amenable to brachytherapy, 
because not technically feasible, should undergo external beam 
boost using three-dimensional treatment planning, conformal 
radiotherapy or IMRT techniques to deliver a minimal total dose of 
65 Gy to the GTV (2000 cGy boost at a dose/fraction of 200 cGy 
in 10 fractions).  The prescription dose is the isodose that 
encompassed at least 97% of the PTV.  No more than 20% of any 
PTV should receive > 110 % of the prescribed dose.  No more than 
1% or 1cc (whichever is smaller) of the tissue outside the PTV will 
receive > 110% of the dose prescribed to the PTV. (02/08/10) 
 
 
IMRT is allowed for all patients independently if a brachytherapy 
boost is to be performed of not. In case that the patient is not 
undergoing brachytherapy the entire plan, including the boost with 
IMRT needs to be submitted. (05/14/2012) 
 
4.245 If overall treatment time for external pelvic RT, whole pelvis 
irradiation to 4500 cGy, exceeds 42 days (6 weeks), or the entire 
external beam plus boost exceed 70 days (10 weeks), the reason for 
the delay must be documented. If interruption of radiation should 
occur for ≥5 consecutive treatment days the protocol Study Chair 
or Co-Chair must be notified. 
 
4.25 
Low Dose Rate (LDR) Intracavitary Brachytherapy  
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 22 - 
Recurrences limited to the superficial mucosa of less than 5 mm 
thickness, can be treated with LDR endocavitary brachytherapy 
techniques. Following the completion of external beam RT, to a dose of 45 
Gy, the patient will receive intracavitary brachytherapy using vaginal 
ovoids or vaginal cylinders or, depending upon the location of the lesion, 
for an additional 30 Gy prescribed to a depth of 0.5 cm, in order to deliver 
a dose to GTV, as defined by physical exam and/or CT scan, of a 
minimum of 75 Gy estimated to a depth of 0.5 cm. In very superficial 
lesions of maximum depth of 2-3 mm, the dose can be prescribed to the 
vaginal surface, for an additional 35 Gy in order to deliver a total dose of 
80 Gy including the contribution from external beam irradiation. The 
implant should adequately cover the involved area with a minimum 
mucosal margin of 3 cm.  
 
The use of vaginal ovoids is highly recommended in patients with 
superficial lesions limited to the apex of the vagina, since it allows the use 
of anterior and posterior packing with subsequent decrease in the dose to 
the bladder and rectum, respectively.  For lesions involving the mid and 
lower vagina, vaginal cylinders should be used. 
 
Rectal dose should be kept ≤ 70Gy and bladder dose ≤ 75Gy including the 
contribution from external beam (4500 cGy) and intracavitary 
brachytherapy.   
 
4.26 
High Dose Rate (HDR) Intracavitary Brachytherapy 
 
Recurrences limited to the superficial mucosa of less than 5 mm 
thickness, can be treated with HDR endocavitary brachytherapy 
techniques. 
 
The patient will receive 3 implants after completing 45 Gy external beam 
irradiation.  At least the proximal 5 cm in length of the vagina should be 
treated for lesions involving the vaginal apex.  The patient will receive a 
total of 3 fractions each one of 700 cGy prescribed to a depth of 5 mm.  In 
case that the entire length of the vagina is to be treated, this should be 
done only with the first implant (700 cGy to a depth of 0.5 cm) and the 
remaining 2 fractions should treat only the proximal 3-5 cm (depending 
upon the extent of the disease at the vaginal apex, providing a distal 
margin of 3 cm). 
 
4.27 
Low Dose Rate Interstitial Brachytherapy 
 
 
 
 
Recurrences limited to the superficial mucosa of more than 5 mm 
thickness, need to be treated with LDR interstitial techniques 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 23 - 
 
Following the completion of external beam radiotherapy to 45 Gy, the 
patient will receive an interstitial implant to deliver a minimum dose of -
80 Gy to the gross tumor volume, as defined by physical exam and/or CT 
scan, depending upon the size of the recurrence.  
 
4.28  High Dose Rate (HDR) Interstitial Brachytherapy 
 
 
Recurrences limited to the superficial mucosa of more than 5mm 
thickness, need to be treated with interstitial techniques, which can be 
utilizing HDR or LDR brachytherapy. 
 
 
Following the completion of external beam RT, to a dose of 45 Gy, the 
patient may receive interstitial brachytherapy using templates and 
interstitial needles on an individualized basis depending on the location 
and extent of the disease.  In addition to a documented clinical exam, all 
patients are required to undergo pre-treatment imaging using either CT or 
MRI to adequately document tumor size and location.  It is recommended 
that interstitial brachytherapy be planned utilizing the diagnostic imaging 
obtained at the time of protocol enrollment, but when in the best interest of 
the patient, a repeat diagnostic study using either CT or MRI can be 
obtained in the final week of external radiation to guide applicator 
placement.  Laparoscopy or laparotomy may be considered to help place 
needles and minimize risk for injury to the small bowel.  If available, the 
use of transabdominal or trans-rectal ultrasound, CT scan, or MRI is 
strongly recommended for guidance during needle placement. 
 
All patients will be required to undergo a post-procedure CT scan of the 
abdomen/pelvis with 2.5mm or smaller slice thickness to be used for HDR 
treatment planning.  The gross tumor with a clinically based expansion 
should be contoured and designated as the High Risk CTV (HR-CTV) as a 
separate structure as delineated by marker seeds, CT scan, or MRI 
imaging.  It is recommended that treating physicians perform an image 
fusion using the pre-implant imaging study that demonstrates the tumor 
volume best.  The dose should be optimized to the CTV with the goals of 
achieving a D90 (dose to 90% of the CTV) ≥ 100% of the prescription dose 
while minimizing the dose to normal organs.  The prescription for HDR 
interstitial brachytherapy will be 5 fractions of 4-6 Gy each, delivered to 
the gross disease as defined by physical exam, CT and/or MRI scans.  
Normal –tissue dosimetry should include descriptions of dose to volumes 
such as to 0.1cm3, 1cm3, and 2cm3 of the bladder, rectum, sigmoid, and 
small bowel.  In all cases, the needle loading should be optimized to limit 
the cumulative dose delivered to 2cm3 of organs at risk from both external 
beam radiation therapy and brachytherapy as follows:  
 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 24 - 
Organ at Risk 
Equivalent Dose at 2Gy per Fraction (EQD2) 
Rectum, 2cm3 
< 70 Gy 
Sigmoid, 2cm3 
< 70 Gy 
Small Bowel, 2cm3 
< 65 Gy 
Bladder, 2cm3 
< 90 Gy 
 
For reference regarding the calculation of EQD2 doses, please use the 
American Brachytherapy Society HDR Radiobiologic Dose Equivalent 
Worksheet at: https://www.americanbrachytherapy.org/guidelines/  
 
It is strongly recommended that patients complete anesthesia and 
applicator placement in the morning, such to allow sufficient time for 
image confirmation and implant planning to occur and the subsequent 
delivery of the first fraction in the afternoon on that first day.  The 
remaining fractions should be delivered over the next two days treating 
patients twice per day with a minimum interfraction interval of 6 hours.  It 
is recommended that treating physicians use an anchoring mechanism 
such as the proprietary locking devise on interstitial applicators or 
adhesive glue if using a disposable template, to assure catheters are stable 
during treatment.  For patients where the interstitial needles are fixed to 
the template, a pre-treatment CT scan immediately prior to the 1st fraction 
and a clinical exam with each remaining fraction is required to confirm 
applicator position.  In situations where adhesive glue is not utilized, a CT 
image dataset should be obtained prior to each HDR fraction, and 
interstitial needles identified.  In cases where the axial, coronal, or sagittal 
displacement is ≥ 5mm in ANY direction, an attempt should be made to 
correctly reposition.  In situations where there is ≥ 5mm displacement and 
needles are unable to be corrected, the treating oncologist should re-plan 
and repeat the dwell position optimization in order to guarantee target 
coverage.  In those cases where an HDR treatment is re-planned, the HR-
CTV and organs at risk should be denoted with a subscript with sequential 
numbering indicative of the brachytherapy plan (ie. HR-CTV1, HR-CTV2, 
etc. or Rectum_HDR1, Rectum_HDR2, etc.). 
 
4.29  Dose Distribution for All Regimens  
 
A four-field box technique with parallel opposed AP/PA and two opposing 
lateral fields or IMRT should be used for the initial pelvic fields.  AP/PA 
only fields are allowed in patients in whom inguino-femoral nodal 
irradiation is indicated.  Dose distribution across clinical target volume 
should not vary more than 5% from the recommended dose.  All fields 
must be treated daily.   
 
Patients with pelvic recurrence not amenable to brachytherapy, because 
not technically feasible, should undergo external beam boost using three-

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 25 - 
dimensional treatment planning, 3D conformal radiotherapy or IMRT 
techniques to deliver a minimal total dose of 65 Gy to the GTV (2000 cGy 
boost at a dose/fraction of 200 cGy in 10 fractions).  
 
4.29  Radiation Equipment 
 
 
4.291 External beam radiation will be delivered using a Linear 
Accelerator with a peak photon energy of 6 MV or greater.  SAD 
of 100 cm is required unless the Tomotherapy device is used. For 
those institutions using IMRT, megavoltage equipment capable of 
delivering static intensity modulation with a multileaf collimator or 
dynamic intensity modulation (using a multileaf collimator or 
tomotherapy) using forward planned or inverse planned IMRT 
treatment planning methods is acceptable. All patients will 
undergo CT based simulation for localization, and verification of 
external RT treatment portals. MRI could be used in pre-treatment 
planning.  All the structures, including gross tumor volume at the 
primary and regional sites (GTVp and GTVr), in addition to the 
clinical target volumes (CTV 1 and CTV2), planning target 
volumes (PTV1 and PTV2) and the normal critical surrounding 
structures should be contoured as above, and delivered doses 
documented. Dose-Vole Histograms (DVH) are to be submitted for 
each one of the indicated volumes and critical structures. 
 
4.292 For Submission via TRIAD™ the structure names must match the 
following list exactly or resubmission will be required 
(04/21/2014) 
 
Standard Name 
Description / Detailed Specification 
GTVp 
Primary GTV. 
Required 
CTVn 
Nodal Lymph nodes as described in protocol 
Required 
CTV_4500 
CTV1 = CTVp+CTVn 
Required 
PTV_4500 
PTV1 : PTV expanded to encompass CTV1 by a 7 mm 
margin  
Required 
PTV_6500* 
PTV2: Primary PTV  (When IMRT is used for boost) 
Required when applicable 
Bladder 
Bladder 
Required 
Femurs 
Femoral Heads 
Required 
Kidneys 
Kidneys 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 26 - 
Required 
Rectum 
Rectum 
Required 
BowelSpace 
Bowel  
Required 
IliacCrests 
Iliac Crests 
Required 
NonPTV 
Unspecfifed tissues (External minus PTVs) 
Required 
External 
External Skin 
Required 
HR_CTV 
Primary GTV + expansions for interstitial HDR 
Brachytherapy 
Required where applicable (HDR Interstitial) 
Rectum_HDR 
Rectum 
Required where applicable (HDR Interstitial) 
Bladder_HDR 
Bladder 
Required where applicable (HDR Interstitial) 
Sigmoid_HDR 
Sigmoid 
Required where applicable (HDR Interstitial) 
Small Bowel_HDR 
Small Bowel Loops 
Required where applicable (HDR Interstitial) 
 
 
4.293   Intracavitary LDR brachytherapy should be delivered using 
Cesium-137.  
 
Intracavitary HDR brachytherapy should be delivered with a single 
Iridium-192 source. 
  
Interstitial LDR brachytherapy should be delivered using Iridium-
192.  
 
Interstitial HDR brachytherapy should be delivered with a single 
Iridium-192 source. 
 
Orthogonal or computed tomography films should be performed 
for each implant to confirm applicator geometry.  For patients 
where the interstitial needles are fixed to the template, a pre-
treatment CT scan immediately prior to the 1st fraction and a 
clinical exam with each remaining fraction is required to confirm 
applicator position.  In situations where a locking mechanism or 
adhesive glue is not utilized, a CT image dataset should be 
obtained prior to each HDR fraction. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 27 - 
4.210  External Radiation Fields   
 
4.2101 Whole Pelvis Field: The external RT target volume should 
encompass, with adequate margins, the gross disease in the pelvis 
and any gross extension to the vagina as well as possible 
microscopic extension to pelvic lymph nodes.  See Section 4.233 
for detailed description of GTV, CTV and PTV.  
 
4.21011 GTVp= Primary GTV in the vagina and/or pelvis. This is 
defined as all gross disease based on clinical pelvic 
examination as well as CT and/or MRI findings. Any gross 
lymph node disease should be as well contoured 
independently as regional-gross tumor volume (GTVr). 
 
4.21012 CTV2= GTVp + 2 cm cranio-caudal and 1.5 cm axial 
margins. A minimum of 3 cm of normal vagina should be 
contoured distally to the gross disease in patients with 
vaginal recurrences.  
 
4.21013 CTV1= CTV2 + the nodal CTV, including the internal 
(hypogastric and obturator), external and common iliac 
lymph node regions. The CTV1 should be delineated using 
the contrast-enhanced (preferably IV contrast administered) 
iliac vessels, in addition to the perinodal soft tissue 
(minimum of 7 mm axial margin around the vessels). On 
the pelvic wall side the margin will exclude the psoas and 
the piriformis muscles. Bone and intraperitoneal small 
bowel should be excluded from the CTV as much as 
possible (leaving at least 5 mm margin around the vessels) 
and providing adequate margin around GTV is obtained 
(margin can be reduced in the axial margin to 1 cm around 
the GTV, when in close proximity to small bowel). 
Approximately 1-2 cm of tissue anterior to the sacrum (S1-
S3) is usually added to the CTV1 for adequate coverage of 
presacral nodes. In addition, the most antero-lateral margin 
of the external iliac nodes that lie just proximal to the 
inguinal canal should be excluded from the CTV1 (nodal 
CTV should stop at the femoral head. Proximately, the 
CTV1 should end 7 mm from the L4-5 interspace to 
account for the PTV1.  
 
4.21014 The PVT1 should provide a 7 mm margin in all directions 
around the CTV1. The PTV2 volume to be treated using 
3D conformal techniques or IMRT in patients that are not 
candidate for brachytherapy boost should encompass the 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 28 - 
CTV2 as defined above with a 7 mm margin in all 
directions. 
 
4.2102 General guidelines in designing the Whole Pelvic Fields 
 
4.21021AP/PA pelvic fields: The superior border will be through 
the L4-5 interspace unless the target volume (e.g. common 
iliac nodes or local disease) would not be encompassed 
adequately in a cephalad direction.  In the latter case, a 2 
cm margin should be added to the highest level of 
pathologic abnormality, but should not be cephalad to the 
L-3/L-4 interspace.  The lateral border will be 2 cm 
beyond the lateral margins of the bony pelvis.  The 
inferior border will be inferior to the obturator foramen or 
the lowest extension of disease with at least a 3 cm 
margin.  If possible, any attempt should be made to spare 
the vulva and perineum particularly in patients with upper 
and mid-vaginal lesions.  If tumor extends to the introitus 
then the fields should “flash” the perineum and vulva. 
 
4.21022 Lateral Pelvis Fields: The anterior border should be 
determined by the PTV1 as defined above, generally 
anterior to the symphysis pubis. The posterior border 
should be placed at least 1.5 cm behind the anterior 
surface of the sacrum.  Attention should be paid to exclude 
as much as possible of the sacral plexus).  The posterior 
wall of the rectum should be excluded providing that the 
gross tumor volume with a 2.5 cm (1.5 cm axial margin to 
the CTV2 and 7 mm additional margin to define the 
PTV2) margin is adequately included in the radiation 
field.  Superior and inferior borders will be the same as for 
the anterior and posterior fields.  If clips are present from 
the lymph node dissection to document the position of the 
lymph nodes, then these should be used as a guide when 
anterior blocks are designed to shield small bowel.  At 
least 3 cm should not be blocked anterior to the L-5 
vertebral body.  Also, the anterior two-thirds of the L-5 
vertebral body should not be blocked in order to 
adequately cover the common iliac nodes with 1.5-2 cm 
margins. 
 
4.211  Radiation therapy quality control and documentation   
 
4.2111 As per Section 4.2. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 29 - 
4.2112 Digital reconstructed radiographs (DRR) of the treatment fields 
with the three-dimensional reconstruction of the GTVp and GTVr 
as well as CTV are to be obtained and submitted for evaluation. 
 
4.2113 Localization or block-check -images of the virtually simulated 
fields are to be obtained in the simulator and/or treatment machine, 
for all the treatment fields independently whether cerrobend blocks 
or multi-leaf collimators are to be used. This applies to the whole 
pelvic radiotherapy fields when IMRT is not used for boost of the 
GTV.  
 
4.2114 For the IMRT boost plans orthogonal films or images with 
isocenter localization shall be obtained. The length of the treatment 
fields should be indicated in the films. These films will not be 
collected but should be held by the institution and available for 
review if requested. 
 
4.2115 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. 
 
4.2116 Tumor diagrams and detailed description of the vaginal lesions are 
required, as some lesions are visible neither by CT or MRI. 
 
4.2117 Polaroid pictures of all treatment portals with the patient in the 
treatment position are recommended.  
 
4.2118 Portal films will be obtained and submitted to the GOG Statistical 
and Data Center with the patient records for the whole pelvic field.   
 
4.2119 Orthogonal simulation films will be taken following the interstitial 
+/- intracavitary brachytherapy implants for planning purposes, 
and CT and/or MRI scans will be required for treatment planning 
in those patients who are treated with HDR interstitial 
brachytherapy.  The films and calculations of the intracavitary 
insertion will be submitted to the GOG Statistical and Data Center 
with the patient records.  A digital treatment plan will need to be 
submitted for each patient treated with HDR interstitial 
brachytherapy including dwell positions and times, and dose 
volume histograms for organs of interest. 
 
4.21110 Copies of the CT or MRI scan showing the relevant tumor 
volume should be submitted to the Statistical and Data Center as 
well. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 30 - 
4.21111 IROC Houston (at U.T. M.D. Anderson Cancer Center will 
supervise the dosimetry quality control for this clinical trial.  To 
participate in the trial, the institutions must demonstrate the ability 
to achieve an accuracy of ±3% in measuring the output of their 
machines and ±5% in delivering the prescribed dose. (04/21/2014) 
 
4.21112 Rapid Review Data Submission for IMRT via TRIAD:  
 
 
 
The following patient treatment data must be electronically 
submitted via TRIAD: Digital Data Submission Information Form 
(DDSI), http://www.rtog.org/CoreLab/TRIAD.aspx Digital 
treatment planning data (digital patient data CT scans, critical 
normal structures, including “unspecified tissue” as per NCI-
IMRT guideline, all CTV/ITV/PTV contours, doses for all 
fraction groups, DVHs for total dose plan), Color Isodose 
Distribution (04/21/2014) 
 
4.212 Expected Toxicity  
 
Gastrointestinal toxicity: Nausea and vomiting may occur, especially after 
the first few treatments.  Intractable nausea and vomiting beyond the first 
few days should arouse suspicion of recurrent tumor or other causes of 
bowel obstruction, as it is rarely seen as a result of radiation alone.  
Consider stool sample for Clostridium difficile toxin.  Increased bowel 
activity with diarrhea can be expected fairly routinely after the first two 
weeks of pelvic and peri-aortic radiation.  It is recommended that 
instructions be given to patients for a low fiber, low fat, and soft diet.  
Most patients will require antidiarrheal medications during therapy.  
 
Should GI toxicity become severe enough to require hospitalization or 
outpatient IV fluid replacement, all treatment should be discontinued 
temporarily until the patient’s condition improves.  Study Chair must be 
notified. 
 
Hematological toxicity: is frequently seen when using a combination of 
pelvic irradiation and concurrent cisplatin. Decline in WBC and platelet 
count should be carefully monitored on a weekly basis. The guidelines for 
dose and treatment modifications are described in Section 6.0. 
 
 
 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 31 - 
5.0 
TREATMENT PLAN AND ENTRY   
 
 
IMRT credentialing for this protocol will be handled by IROC Houston (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”. (10/8/2008) (04/21/2014) 
 
5.1 
Before any patient is enrolled on this study the treating radiation oncologist must 
complete a Knowledge Assessment Questionnaire found on the IROC Houston 
website. (10/8/2008) (04/21/2014) 
 
5.11 
IMRT credentialing requirements when IMRT is planned:   
 
Institutions must be credentialed for IMRT by IROC Houston for this 
protocol prior to enrolling patients on to 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 on the IROC Houston website. The treatment 
plan for irradiation of the phantom must be submitted electronically via 
TRIAD (see Section 5.13). Institutions that have been previously 
credentialed for IMRT via the Head and Neck phantom or the Pelvic 
phantom can determine which additional requirements must be completed 
by filling out the “Credentialing Status Inquiry” form on the IROC 
Houston website. IROC Houston will then issue credentials for this 
protocol to the institution and notify the GOG Statistical and Data Center. 
 
Institutions that have not been credentialed for IMRT by IROC Houston at 
M.D. Anderson Cancer Center for this protocol must apply for IMRT 
certification as described in the following sections. (04/21/2014)  
 
5.12 
Each Institution must complete the IMRT Facility Questionnaire available 
on the IROC Houston web site by selecting “protocol 0238”. Each 
institution must submit the completed IMRT Facility Questionnaire 
online. (04/21/2014) 
 
 
Institution and/or peer-reviewed documentation of target position 
reproducibility [planning treatment volume (PTV) and clinical target 
volume (CTV)] must be consistent with Section 4.29.   
 
5.13 
Each institution must complete the following process to access TRIAD 
PRIOR to any patient enrollment: (04/21/2014) 
 
5.131 Digital RT Data Submission Using TRIAD (04/21/2014)  
 
TRIAD is the American College of Radiology’s (ACR) 
image exchange application and it is used by IROC 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 32 - 
Houston (RPC). TRIAD provides sites participating in 
clinical trials a secure method to transmit DICOM RT and 
other objects. TRIAD anonymizes and validates the images 
as they are transferred. The following process must be 
completed prior to enrolling patients on the trial. 
 
TRIAD Access Requirements: 
 Site physics staff who will submit images through TRIAD will 
need to be registered with The Cancer Therapy Evaluation 
Program (CTEP) and have a valid and active CTEP Identity 
and Access Management (IAM) account.  
 To submit images, the site physics user must have been 
assigned the 'TRIAD site user' role on the relevant Group or 
CTSU roster, and should follow their procedures for 
assignment of roster roles.  
 
TRIAD Installations: 
When a user applies for a CTEP-IAM account with 
proper user role, he/she will need to have the TRIAD 
application installed on his/her workstation to be able to 
submit images. TRIAD installation documentation can 
be found on the IROC Houston web site.    
 
This process can be done in parallel to obtaining your 
CTEP-IAM account username and password.  
 
If you have any questions regarding this information, 
please send an e-mail to the TRIAD Support mailbox at 
TRIAD-Support@acr.org. 
 
 
 
  
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 33 - 
5.2 
Registration Procedures (04/21/2014) 
 
 
Food and Drug Administration (FDA) regulations and National Cancer Institute 
(NCI) policy require all investigators participating in any NCI-sponsored clinical 
trial to register and to renew their registration annually. 
 
Registration requires the submission of: 
 
 a completed Statement of Investigator Form (FDA Form 1572) with an 
original signature 
 a current Curriculum Vitae (CV) 
 a completed and signed Supplemental Investigator Data Form (IDF) 
 a completed Financial Disclosure Form (FDF) with an original signature 
 
Fillable PDF forms and additional information can be found on the CTEP website 
at <http://ctep.cancer.gov/investigatorResources/investigator_registration.htm>.  
For questions, please contact the CTEP Investigator Registration Help Desk by 
email at <pmbregpend@ctep.nci.nih.gov>. 
 
5.21 
CTEP Associate Registration Procedures / CTEP-IAM Account 
 
The Cancer Therapy Evaluation Program (CTEP) Identity and Access 
Management (IAM) application is a web-based application intended for 
use by both Investigators (i.e., all physicians involved in the conduct of 
NCI-sponsored clinical trials) and Associates (i.e., all staff involved in the 
conduct of NCI-sponsored clinical trials). 
 
Associates will use the CTEP-IAM application to register (both initial 
registration and annual re-registration) with CTEP and to obtain a user 
account. 
 
Investigators will use the CTEP-IAM application to obtain a user account 
only. (See CTEP Investigator Registration Procedures above for 
information on registering with CTEP as an Investigator, which must be 
completed before a CTEP-IAM account can be requested.) 
 
An active CTEP-IAM user account will be needed to access all CTEP and 
CTSU (Cancer Trials Support Unit) websites and applications, including 
the CTSU members’ website. 
 
Additional information can be found on the CTEP website at 
<http://ctep.cancer.gov/branches/pmb/associate_registration.htm>.  For 
questions, please contact the CTEP Associate Registration Help Desk by 
email at <ctepreghelp@ctep.nci.nih.gov>. 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 34 - 
 
5.22 
CTSU Registration Procedures 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU). 
 
5.221 IRB Approval:   
 
Each investigator or group of investigators at a clinical site must obtain 
IRB approval for this protocol and submit IRB approval and supporting 
documentation to the CTSU Regulatory Office before they can be 
approved to enroll patients.  Study centers can check the status of their 
registration packets by querying the Regulatory Support System (RSS) site 
registration status page of the CTSU members’ website by entering 
credentials at https://www.ctsu.org.  For sites under the CIRB initiative, 
IRB data will automatically load to RSS. 
 
5.222 Downloading Site Registration Documents:   
 
Site registration forms may be downloaded from the GOG-0238 protocol 
page located on the CTSU members’ website.  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. 
Go to https://www.ctsu.org and log in to the members’ area using your 
CTEP-IAM username and password 
Click on the Protocols tab in the upper left of your screen 
Click on the NCTN NRG link to expand, then select trial protocol # 0238 
Click on the Site Registration Documents link 
 
5.223 Requirements For GOG-0238 Site Registration: 
 
• 
CTSU IRB Certification (for sites not participating via the NCI CIRB) 
• 
CTSU IRB/Regulatory Approval Transmittal Sheet (for sites not 
participating via the NCI CIRB)  
• 
CTSU RT Facilities Inventory Form   
NOTE:  Per NCI policy all institutions that participate on protocols with a 
radiation therapy component must participate in IROC Houston 
monitoring program.  If this form has been previously submitted to CTSU 
it does not need to be resubmitted unless updates have occurred at the RT 
facility 
 
 
5.224 Submitting Regulatory Documents:  
 
Submit completed forms along with a copy of your IRB Approval and 
Model Informed Consent to the CTSU Regulatory Office, where they will 
be entered and tracked in the CTSU RSS.  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 35 - 
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone: 1-866-651-2878 
Fax: 215-569-0206 
E-mail: CTSURegulatory@ctsu.coccg.org (for regulatory document 
submission only) 
 
5.225 Checking Your Site’s Registration Status: 
 
Check the status of your site’s registration packets by querying the RSS 
site registration status page of the members’ section of the CTSU website.  
(Note: Sites will not receive formal notification of regulatory approval 
from the CTSU Regulatory Office.) 
Go to https://www.ctsu.org and log in to the members’ area using your 
CTEP-IAM username and password 
Click on the Regulatory tab at the top of your screen 
Click on the Site Registration tab 
Enter your 5-character CTEP Institution Code and click on Go  
 
5.3 
Patient Entry and Registration (04/21/2014) 
 
Patient enrollment will be facilitated using the Oncology Patient Enrollment 
Network (OPEN).  OPEN is a web-based registration system available on a 24/7 
basis.  To access OPEN, the site user must have an active CTEP-IAM account 
(check at < https://eapps-ctep.nci.nih.gov/iam/index.jsp >) and a 'Registrar' role 
on either the LPO or participating organization roster. 
 
All site staff will use OPEN to enroll patients to this study.  It is integrated with 
the CTSU Enterprise System for regulatory and roster data.  OPEN can be 
accessed at https://open.ctsu.org or from the OPEN tab on the CTSU members’ 
side of the website at https://www.ctsu.org. 
 
All site staff will use OPEN to enroll patients to this study.  OPEN can be 
accessed on the GOG web menu page by clicking on the OPEN link.  
  
Prior to accessing OPEN, site staff should verify the following: 
  
 
All eligibility criteria have been met within the protocol stated 
timeframes. Site staff should use the registration forms provided on the 
group web site as a tool to verify eligibility. 
 
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable).  
  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 36 - 
Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information.   Please print this confirmation for your 
records.  
 
Access requirements for OPEN: 
  
 
Site staff will need to be registered with CTEP and have a valid and active 
CTEP-IAM account. This is the same account (user id and password) used 
for the CTSU members' web site.  
 
To perform registrations, the site user must have been assigned the 
'Registrar' role on the GOG or CTSU roster.  
 
To perform registrations you must have an equivalent 'Registrar' role on 
the Lead Group roster.  Role assignments are handled through the Groups 
in which you are a member.  
  
Note:  The OPEN system will provide the site with a printable 
confirmation of registration and treatment information.   Please print this 
confirmation for your records.  
  
Further instructional information is provided on the CTSU members' web 
site OPEN tab or within the OPEN URL. For any additional questions 
contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com.  
 
 
5.31 
The institution will enter the patient's name, GOG number, and assigned 
regimen in the appropriate place in their Log Book to verify the patient's 
entry. 
 
5.4 
Randomization and Treatment Plan   
 
5.41 
Radiation Therapy Plan: (04/21/2014) 
 
Please note that all institutions must electronically submit the treatment 
plan for all patients via TRIAD when IMRT is planned. See section 5.131 
for details on setting up a TRIAD account.   After the data has been 
submitted via TRIAD, complete a DDSI information form found as 
http://www.rtog.org/CoreLab/TRIAD.aspx.  The case will be processed in 
preparation for rapid review.  A rapid review will be performed on all 
patients to receive IMRT PRIOR TO DELIVERING ANY PROTOCOL 
TREATMENT. The rapid review will be conducted by IROC Houston in 
collaboration with a GOG designated radiation oncologist and suggestions 
regarding protocol compliance will be forwarded to the participating 
institution‘s radiation oncologist. 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 37 - 
5.42 
Patients with recurrent endometrial carcinoma, limited to the pelvis, after 
surgery with or without adjuvant chemotherapy, who have fulfilled the 
eligibility requirements according to Section 3.0 will receive random 
treatment allocation to one of the following treatment arms: 
 
Regimen I:  Whole pelvic external beam radiation followed by vaginal 
brachytherapy  
 
versus 
 
Regimen II:  Whole pelvic external beam radiation with concurrent 
weekly cisplatin followed by vaginal brachytherapy  
 
5.43 
Radiation treatment will be administered daily, Monday through Friday, 
for approximately five weeks followed by brachytherapy treatments, all in 
accordance with Section 4.2. 
 
The patients randomized to receive cisplatin will receive it weekly, 
preferably on Mondays, for 5 weeks at a dose of 40 mg/m2 /week 
(maximum total dose of 70 mg/week). 
 
5.44  Concurrent Cisplatin Administration 
 
500 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 will be diluted in 250 cc 0.9% sodium chloride and 
administered over one or two hours (rate of 1 mg of cisplatin per 
minute).  Details of pre- and post-hydration are left to the discretion of the 
treating physician, but at least 1000 cc 0.9% sodium chloride prior to 
cisplatin and another 500-1000 cc 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 radiation therapy (day 
1), preferably approximately four hours prior to radiation therapy, 
cisplatin will be repeated as above on Days 8, 15, 22, and 29 (preferably 
Mondays) of external radiation therapy.   
 
5.441 Recommended Pre-medications for Cisplatin 
 
All pre-medications should be administered at least 15 to 30 
minutes prior to cisplatin administration. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 38 - 
 
 
 
 
 
Palonosetron 0.25 mg IV 
Granisetron 2 mg or Ondansetron 12 mg IV  
 
 
 
 
Dexamethasone 20 mg IV 
Diphenhydramine 50 mg IV  
 
 
 
 
Ranitidine 150 mg IVPB PRN 
 
 
 
 
Lorazepam 1 mg IV/PO PRN 
 
5.442 Recommended medication for delayed nausea and vomiting 
 
 
Dexamethasone 4 mg PO bid x 2 days and 2 mg PO bid x 2 days 
 
Aprepitant 125 mg, 80 mg, 80 mg PO daily x 3 days 
 
Compazine 10 mg PO q 4-6 h PRN 
 
5.5 
Criteria for removal from treatment   
 
5.51 
Inability to tolerate the therapy because of toxicity. 
 
5.52 
Patients may withdraw from the study at any time for any reason.  
 
5.53 
Development of disease progression. 
 
5.54 
Any clinical adverse event or intercurrent illness, which, in the opinion of 
the treating physician, indicates that continued treatment with all study 
therapy (radiation therapy with/without cisplatin) is not in the best interest 
of the patient. 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 39 - 
6.0 
TREATMENT MODIFICATIONS   
 
It is in the patient’s best interest to receive the radiation therapy on time.  Every effort 
should be made to encourage the patient to comply with the treatment prescribed where 
possible.  When toxicity is encountered, the chemotherapy and radiation will be held as 
indicated in Tables 1 and 2, on those patients randomized to receive chemo-radiation 
therapy, until resolution.  Restart radiation therapy and chemotherapy at that point, at full 
doses.  
 
6.1 
Hematologic Adverse Effects  
 
6.11 
Radiotherapy  
 
A decline in ANC and platelet counts to Grade 2 (<1500-1000/mm3, ANC 
and <75,000-50,000/mm3, platelets) may frequently occur.  A CBC should 
be obtained weekly during radiation therapy, and if the ANC 1000/mm3 
or platelet count <50,000/mm3, Grade 3 or worse toxicity, a CBC should 
be obtained at least every other day while radiation is on hold until 
recovery to Grade 2 or less.  
 
Radiation therapy will not have to be interrupted for uncomplicated   
hematological toxicity (ANC > 1000/mm3, platelets > 50,000/mm3, no 
neutropenic fever).  (10/08/08) 
 
6.12 
Cisplatin 
 
Febrile neutropenia requiring intravenous antibiotics or thrombocytopenia 
with bleeding requiring platelet transfusion will require holding cisplatin 
and radiation therapy until symptoms resolve (fever or bleeding) and 
neutropenia is resolved to Grade 2 or less (ANC ≥1000/mm3) and 
thrombocytopenia is resolved to Grade 2 or less (platelets ≥50,000/mm3).  
Resume treatment as planned.  
 
Neutropenia, which is uncomplicated, Grade 4 ANC <500/mm3, or Grade 
3-4 thrombocytopenia, <50,000 mm3, lasting less than 7 days requires 
holding only chemotherapy until only Grade 3 neutropenia, ANC <1000-
500/mm3, and only  Grade 2 thrombocytopenia, <75,000-50,000/mm3.  
Radiation therapy will be interrupted until ANC≥1000/mm3, Grade 3 or 
less, and thrombocytopenia ≥ 50,000/mm3, Grade 2 or less.  Resume 
chemotherapy as planned.  
 
Prolonged Grade 4 neutropenia or Grade 3-4 thrombocytopenia lasting 
more than 7 days past the interruption of chemotherapy (14 days since the 
last dose received) should cause interruption of radiation therapy until 
ANC 500/mm3 (Grade 3 or better) and platelets 50,000/mm3 (Grade 2 
or better).  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 40 - 
 
Patients must have no worse than Grade 3 neutropenia (ANC 500/mm3) 
and Grade 2 thrombocytopenia (platelets 50,000/mm3) to receive their 
next weekly dose of chemotherapy. 
 
Treatment toxicities will be reported using the NCI CTCAE v3.0. 
 
Table 1.  Treatment Modifications for Hematologic Toxicity   
 
Toxicity NCI CTCAE v3.0 
Grade 
Radiation (both regimens) 
Cisplatin 
Neutropenia 
 
 
1 (1500/mm3 - LLN) 
Maintain dose level 
Maintain dose level 
2 (1000-1499/mm3) 
Maintain dose level 
Maintain dose level 
3 (500-999/mm3) 
Maintain dose level 
Maintain dose level 
4 (< 500/mm3) 
Uncomplicated 
Hold treatment for 
maximum of 2 weeks until 
recovered to ≤ grade  3  
Hold treatment for a 
maximum of 2 weeks until 
recovered to grade ≤ grade 3  
Resume full dose1 
Neutropenic fever 
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.   
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.  
Resume full dose1 
Thrombocytopenia 
 
 
1 (75,000/mm3 - LLN) 
Maintain dose level  
Maintain dose level  
2 (50,000- 74,999/mm3) 
Maintain dose level  
Maintain dose level  
3 (25,000- 49,999/mm3) 
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.   
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.  
Resume full dose1 
4 (< 25,000/mm3) 
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.   
Hold treatment for a 
maximum of 2 weeks until 
recovered to ≤ grade 2.  
Resume full dose1 
1Repeat lab work twice weekly and resume treatment based on this table. 
 
6.2 
Gastrointestinal Adverse Effects 
 
Grade 1-2 nausea/vomiting with the onset of concomitant cisplatin and radiation 
therapy, and Grade 1 diarrhea after 1-2 weeks of radiation therapy may be 
expected.  Patients may receive the investigator’s choice of drugs for the control 
of nausea and vomiting associated with the cisplatin administration.  Nausea, 
vomiting, and diarrhea during the course of radiation therapy may be treated 
symptomatically by antiemetic and antidiarrheal medications, and dietary 
modifications.  Intractable nausea and vomiting beyond the first few days after 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 41 - 
cisplatin chemotherapy should arouse suspicion of other causes such as bowel 
obstruction.  Consider sending stool sample for Clostridium difficile toxin. 
 
6.21 
Radiotherapy 
 
Radiation therapy will be interrupted in patients where hospitalization or 
IV fluid replacement is necessary (Grade ≥ 2).  Radiation therapy should 
be resumed as soon as the patient has improved to allow oral intake and 
not require IV hydration (Grade ≤ 1).  Every effort should be made to 
control diarrhea by dietary restriction and antiperistaltic drugs.  This 
interruption should preferably be for no longer than one week. 
 
Study Chair or Co-Chair must be called whenever interruption of radiation 
therapy has lasted more than 5 treatment days.   
 
6.22 
Cisplatin 
 
Antiemetics should be used prophylactically (See Section 5.442).  
(08/08/08) 
 
Table 2.  Dose Modifications for Gastrointestinal Toxicity 
 
Toxicity 
NCI CTCAE v3.0 Grade1 
Radiation (both regimens) Cisplatin 
Diarrhea 
 
 
2 despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade 
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
3 despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade 
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
3, recurrent despite maximal medical 
management 
Hold treatment for a maximum 
of 2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2   
4 despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
Nausea/Vomiting 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 42 - 
Toxicity 
NCI CTCAE v3.0 Grade1 
Radiation (both regimens) Cisplatin 
2 despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
≥3 despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2   
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
≥3, recurrent despite maximal medical 
management 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ 
grade 1.  Resume treatment as 
planned, providing no other 
toxicities  grade 2 
Hold treatment for a maximum of 
2 weeks, until recovered to ≤ grade
1.  Resume treatment as planned, 
providing no other toxicities  
grade 2   
1 For < CTCAE v3.0 Grade 2 toxicity not described above, maintain dose level of all agents. 
 
6.3 
Renal/Genitourinary Adverse Effects 
 
Increased frequency with dysuria may occur in some patients.  This may be 
treated symptomatically with antispasmodics and increased fluid intake.  Urinary 
tract infection should be ruled out if the symptoms persist. 
 
6.31 
Radiotherapy 
 
Radiation therapy may be interrupted for up to one week for Grade 3 or 4 
bladder toxicity at the discretion of the investigator.  Study Chair must be 
called whenever interruption of radiation therapy is considered. 
 
6.32 
Cisplatin 
 
Renal Adverse Effects 
 
If creatinine rises to greater than 2.0 mg/dl, obtain creatinine clearance 
(CrCl).  Consider renal ultrasound.  If CrCl is greater than or equal to 50 
ml/min, continue therapy.  If CrCl is less than 50 ml/min, hold treatment 
and check CrCl weekly.  When the CrCl is greater than or equal to 50 
ml/min, or the serum creatinine is less than 2.0 mg/dl, resume therapy at 
75% of the planned dose.  Persistence of CrCl less than 50 ml/min or 
serum creatinine greater than 2.0 mg/dl for more than two weeks requires 
notification of the Study Chair, and patient’s study therapy will be 
stopped. 
 
Selective renal tubular defects are sometimes observed.  Hypocalcemia 
with hypomagnesemia and hypokalemia are common and potentially 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 43 - 
severe.  Replacement of magnesium, calcium, and potassium are usually 
effective.  Severe tubular defects, although rare, may require chronic 
replacement therapy. 
 
Diagnostic tests for alternative mechanisms of hypocalcemia (for example, 
GI or metabolic) are suggested. 
 
The formula for calculating the creatinine clearance is: 
 
 
98
(0.8*(
20))
0.9*
Age
CrCl
Scr









 
 
where CrCl = creatinine clearance in ml/min 
Age = patient’s age in years (from 20-80) 
Scr = serum creatinine in mg/100 ml 
 
6.4 
Cutaneous Adverse Effects 
 
 
 
6.41 
Radiation 
 
Grade 1-2 skin reactions may occur especially in the intertrigonous and 
peri-anal regions within the radiation fields.  The skin reaction may be 
more prominent in those patients requiring irradiation of the inguino-
femoral lymph node areas.  Use of skin care as well as adequate hygiene 
measures are to be discussed with the patient at the initiation of therapy. 
 
 
Radiation therapy may be temporarily interrupted for up to one week for 
Grade 3-4 skin toxicity at the discretion of the radiation oncologist. 
 
6.42 
Cisplatin 
 
Chemotherapy will be resumed at the planned dose once toxicity has 
resolved.  
 
6.5 
Treatment of Hypersensitivity Reactions to Cisplatin: 
 
6.51 
In each case of a hypersensitivity reaction to cisplatin the infusion should 
be stopped and tubing disconnected.  Administer epinephrine, 
bronchodilators, antihistamines, glucocorticoids, intravenous fluids, 
vasopressor agents, oxygen, etc., as medically indicated.  Cisplatin will be 
discontinued following the first hypersensitivity reaction. 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 44 - 
 
6.6 
Radiotherapy Treatment Method Modifications (10/8/2008) 
 
Institutions may NOT submit a plan for non-IMRT treatment and then switch to 
IMRT treatment during the course of the study. If IMRT is planned initially and 
an institution is considering administering another type of radiotherapy, then the 
study chair must be consulted before any other radiotherapy treatment plan 
begins. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 45 - 
7.0 
STUDY PARAMETERS  
 
7.1 
Observations and Tests 
 
The following observations and tests are to be performed and recorded on the 
appropriate form(s): 
*   Radiation Therapy summary plan should be known prior to entry. Specify type of boost on the Fast Fact Sheet 
(FFS). 
** X-ray of chest may be done first, and if abnormal a CT scan of the chest should be done. If the patient is unable to 
tolerate contrast, then MRI with IV gadolinium should be performed (10/8/08) 
1. 
Must be obtained within 28 days prior to initiating protocol therapy.  
Parameter 
Prior to 
study 
entry/Pre-
Therapy 
Weekly 
during 
therapy 
Upon 
completion 
of study 
therapy 
Every month 
for the  first 3 
months after 
completion of 
therapy 
Every 3 months 
after therapy for the 
1st 2 years then 
every 6 months for 
the next 3 years. 
 
History & Physical 
 
1 
 
X 
 
 
X 
 
 
 
X 
 
Radiation treatment 
plan 
 
1* 
 
 
 
 
 
GOG Performance 
Status 
2 
 
X 
 
X 
 
 
 
X 
  
Toxicity Assessment 
 
 
X 
 
X 
 
X 
 
X 
 
CT scan of  Chest, 
abdomen, pelvis   
 
1** 
 
 
 
X 
 
 
8 
 
CBC/Differential/ 
Platelets 
 
2 
 
3 
 
X 
 
 
 
4 
Electrolytes,  BUN, 
Creatinine, Creatinine 
Clearance (CrCl), 
Calcium (CA), 
Magnesium (Mg), 
Phosphorous (PO4) 
 
2 
 
X 
 
X 
 
 
 
X 
Bilirubin, SGOT, 
Alkaline Phosphatase, 
LDH 
 
2 
 
 
X 
 
X 
 
X 
Pap Smear 
 
 
5 
 
5 
Barium enema 
6 
 
 
 
 
Proctoscopy 
6 
 
 
 
 
Cytoscopy 
6 
 
 
 
 
Renal Ultrasound 
6 
 
 
 
 
EKG 
1 
 
 
 
 
Audiogram 
7 
 
 
 
7 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 46 - 
2. 
Must be obtained within 14 days prior to initiating protocol therapy. 
3. 
If Grade 4 neutropenia is documented (ANC <500/mm3), obtain twice per week until resolved to no worse than 
Grade 3. 
4. 
When clinically indicated 
5. 
Recommended 
6. 
Optional 
7. 
Required in all patients with a history of hearing loss.  Must be obtained within 28 days prior to initiating protocol 
 
therapy.  Repeat during therapy every other cycle or more frequently as clinically indicated. 
8. 
Every 6 months during follow-up.  (10/8/08) 
 
 
7.2 
PATHOLOGY REQUIREMENTS (10/18/2010)  
 
Stained pathology slides are required for central review by the GOG Pathology 
Committee to confirm eligibility for the protocol.  At least one representative 
H&E stained slide (or slides) demonstrating the primary site, histologic cell type, 
and grade will be required, as well as at least one representative slide 
documenting the recurrent tumor.  Recurrent disease in the pelvis must be 
histologically documented for eligibility for this protocol. 
 
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 stained slides, pathology reports 
and Form F to the GOG Statistical and Data Center.  Please see Section 10.2 for 
additional requirements and instructions. 
 
7.3 
TRANSLATIONAL RESEARCH (10/18/2010) 
  
Not applicable. 
 
7.4 
QUALITY OF LIFE ASSESSMENTS (10/18/2010) 
Not applicable. 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 47 - 
8.0 
EVALUATION CRITERIA  
 
8.1 
Parameters of Outcome – GOG RECIST Criteria 
 
8.11 
Measurable disease is defined as at least one lesion that can be accurately 
measured in at least one dimension (longest dimension to be recorded).  
Each lesion must be  20 mm when measured by conventional techniques, 
including palpation, plain x-ray, CT, and MRI, or  10 mm when 
measured by spiral CT.   
 
8.12 
Baseline documentation of “Target” and “Non-Target” lesions 
 
All measurable lesions up to a maximum of 5 lesions per organ and 10 
lesions in total representative of all involved organs should be identified as 
target lesions and will be recorded and measured at baseline.  Target 
lesions should be selected on the basis of their size (lesions with the 
longest dimension) and their suitability for accurate repetitive 
measurements by one consistent method of assessment (either by imaging 
techniques or clinically).  A sum of the longest dimension (LD) for all 
target lesions will be calculated and reported as the baseline sum LD.  The 
baseline sum LD will be used as reference to further characterize the 
progression of the measurable dimension of the disease. 
 
All other lesions (or sites of disease) should be identified as non-target 
lesions and should also be recorded at baseline.  Measurements are not 
required and these lesions should be followed as “present” or “absent”. 
 
All baseline evaluations of disease status should be performed as close as 
possible to the start of treatment and never more than 4 weeks before the 
beginning of treatment. 
 
Measurement of the longest dimension of each target lesion size is 
required for follow-up.  Change in the sum of these dimensions affords 
some estimate of change in tumor size and hence therapeutic efficacy.  All 
disease must be assessed using the same technique as baseline.  
 
8.13 
Definition of disease progression 
 
Progression for patients with measurable disease is defined as ANY of the 
following: 
 
 At least a 20% increase in the sum of LD target lesions taking as 
reference the smallest sum LD recorded since study entry  
 In the case where the ONLY target lesion is a solitary pelvic mass 
measured by physical exam which is not radiographically 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 48 - 
measurable, a 50% increase in the LD is required taking as 
reference the smallest LD recorded since study entry 
    The appearance of one or more new lesions   
    Death due to disease without prior objective documentation of 
progression 
    Global deterioration in health status attributable to the disease 
requiring a change in therapy without objective evidence of 
progression  
    Unequivocal progression of existing non-target lesions, other than 
pleural effusions without cytological proof of neoplastic origin, in 
the opinion of the treating physician (in this circumstance an 
explanation must be provided) 
 
 
Progression for patients with non-measurable disease is defined as 
increasing clinical, radiological, or histological evidence of disease 
since study entry.   
 
 
 
 
8.14 
Survival is the observed length of life from entry into the study to death or 
the date of last contact. 
 
8.15 
Progression-Free Survival is the period from study entry until disease 
progression, death, or date of last contact. 
 
8.16 
Subjective Parameters including performance status, specific symptoms, 
and side effects are graded according to the CTCAE. 
 
 
8.17 
Classification of recurrence at study entry   
The type of recurrence will be classified for each patient as either  
1) an isolated vaginal recurrence, defined as a recurrence of endometrial 
carcinoma limited to the vagina with no evidence of pelvic recurrence as 
identified clinically and by CT scan or MRI, or  
2) any recurrence situated in the pelvis.  Recurrences that are evident in 
both the pelvis and the vagina are to be included in the pelvic recurrence 
group.    
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 49 - 
9.0 
DURATION OF STUDY 
 
 
The patient can refuse study treatment at any time.  All patients will be followed (with 
completion of all required case report forms) for a minimum of 5 years after completion 
of therapy unless consent is withdrawn. 
 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 50 - 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES   
 
10.1 
ADVERSE EVENT REPORTING FOR A COMMERCIAL AGENT 
(04/21/2014) 
   
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.  
 
 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 AEs to the study sponsor is 
specified in the Statement of Investigator, Form FDA-1572.  In signing the 
FDA-1572, the investigator assumes the responsibility for reporting AEs 
to the NCI.  In compliance with FDA regulations, as contained in 21 CFR 
312.64, AEs should be reported by the investigator. 
 
10.13 Phase 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 
 
From the period of protocol activation through June 30, 2011, Common 
Terminology Criteria for Adverse Events (CTCAE) version 3.0 (CTCAE 
v3.0) are utilized for defining and grading specific adverse events reported 
through the CTEP-AERS system. (5/23/2011) 
 
Beginning July 1, 2011, the NCI Common Terminology Criteria for 
Adverse Events (CTCAE) v 4.0 will be utilized for AE reporting 
through the CTEP-AERS system. CTCAE v 4.0 is located on the 
CTEP website at 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/c

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 51 - 
tc.htm.  All appropriate treatment areas should have access to a copy 
of this Version of CTCAE.  CTCAE v 4.0 definition is also available 
on the GOG member web site (https://gogmember.gog.org under 
MANUALS). (5/23/2011) 
 
 
 
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: 
CTEPAERS 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 a CTEP-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. 
 
 
Any event that results in persistent or significant disabilities/incapacities, congenital 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 52 - 
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-AERSExpedited Reporting Requirements for 
Phase 2 and 3 Trials Utilizing a Commercial Agent: 
 
 There are no additional instructions or exceptions to CTEP-AERS expedited reporting 
requirements for this protocol. 
 
10.14 Procedures for Expedited Adverse Event Reporting: (10/18/2010) 
 
10.141 CTEP-AERS Expedited Reports: 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.  
 
Up until June 30, 2011, AML/MDS events must be reported via 
CTEP-AERS (in addition to your routine AE reporting 
mechanisms).  In CTCAE v3.0, the event can be reported as:  
“Secondary malignancy-Other (specify)”. (5/23/2011) 
 
Starting July 1, 2011 when use of CTCAE v4.0 begins: 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) Myelodysplastic syndrome, or 3) Treatment 
related secondary malignancy. (5/23/2011) 
 
In the rare event when Internet connectivity is disrupted a 24-hour 
notification is to be made to NCI by telephone at: 301-897-
7497.  An electronic report MUST be submitted immediately upon 
re-establishment of internet connection. Please note that all paper 
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 AEs reported through CTEP-AERS will also be included 
with the quarterly CDUS data submissions. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 53 - 
10.2 
GOG DATA MANAGEMENT FORMS (10/18/2010) 
 
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.  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.  Note:  Pathology materials (Form F, path report, and slides) 
must be submitted together via postal mail or the forms may be uploaded 
using the Upload feature in SEDES. Additionally, radiation materials (forms, 
copies, films, reports, etc) must be submitted together via postal mail. 
(10/18/2010) 
 
Form 
Due within 
Copies* 
Comments 
Weeks 
Event 
Knowledge Assessment 
0 
Prior to Registration 
1 
Available at 
http://irochouston.mdanderson.org  
under ‘Credentialing.’ (10/08/08) 
(04/21/2014) 
Brief Description of 
Radiation Therapy Plan 
0 
Registration 
1 
Specify type of boost planned on Fast 
Fact Sheet 
Form R 
 
2 
 
Registration 
 
1 
 
Submit via SEDES 
Form OSR 
2 
Registration 
1 
Submit via SEDES; report site of 
disease as vaginal, pelvic or both and 
report any disease resection prior to 
entry 
Form DR 
Form BDR 
4 
4 
Registration 
Registration 
1 
1 
Submit via SEDES 
Available in SEDES for print only 
Form D2M – baseline 
assessment 
4 
Registration 
1 
Submit via SEDES; report any tumor 
present at baseline as non-target 
lesions if non-measurable 
Pathology requirements 
Primary diagnosis: 
Form F 
Pathology Report 
Slides  
Recurrence diagnosis: 
Form F  
Pathology Report 
Slides  
 
 
6 
6 
6 
 
6 
6 
6 
 
 
Registration 
Registration 
Registration 
 
Registration 
Registration 
Registration 
 
 
2 
2 
** 
 
2** 
2** 
** 
 
 
All forms may be uploaded in SEDES 
or mailed via postal mail. All slides 
must be sent via postal mail. 
See below 
Radiation Materials: 
- daily treatment reports 
- CT/MRI showing  
relevant tumor volume 
External beam: 
4 
Completion of 
therapy 
 
2 
1 
 
 
Forms G, HDRV, LDRV, and IR  
must be submitted via SEDES.  Paper 
copies should also be submitted with 
radiation materials via postal mail. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 54 - 
Form 
Due within 
Copies* 
Comments 
Weeks 
Event 
- simulation films or 
digitally reconstructed 
radiograph  
- portal films 
- dosimetry calculation 
- Isodose distribution       
curves 
- Form G 
Brachytherapy: 
- orthogonal simulation 
films for each 
intracavitary 
placement 
- Implant films  
- dosimetry calculation 
- isodose distribution 
curves for each 
intracavitary 
placement 
- Form HDRV or Form 
LDRV 
Interstitial: 
- Films for all insertions 
- Activity of needles  
- A diagram locating 
each needle 
- Summary of active 
dwell positions and 
times for HDR 
insertions 
- Dosimetry calculations 
for reported doses 
- Dose distribution for 
each insertion 
- Form IR 
- Digital Treatment Plan 
for HDR interstitial 
implants 
- Dose Volume 
Histogram (DVH) for 
HDR interstitial 
insertions 
IMRT: 
- dosimetry calculations 
- Dose Volume 
Histograms (DVH) 
 
1 
 
 
 
1 
2 
2 
 
2 
 
1 
 
 
 
1 
2 
2 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
1 
1 
 
 
1 
 
 
 
 
 
1 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 55 - 
Form 
Due within 
Copies* 
Comments 
Weeks 
Event 
Form D2R*** 
2 
Completion of each 
week of external 
radiation 
1 
Submit via SEDES 
Form T**** 
2 
Beginning of each 
subsequent week of 
external radiation 
and completion of 
all study therapy 
1 
 
Submit via SEDES 
 
Form D2M 
4 
Chest, abdomen, and 
pelvis imaging and 
clinical tumor 
measurements 
1 
Submit via SEDES 
Form Q0 
 
2 
Completion of study 
treatment  
1 
Submit via SEDES 
Form TLC 
2 
Each 6 month 
follow-up toxicity 
assessment  
1 
Submit via SEDES 
until disease progression is 
documented 
Form Q 
 
2 
Disease progression; 
death; normal 
follow-up; change in 
treatment 
1 
Submit via SEDES 
quarterly for 2 years, semi-annually 
for 3 more years 
    *The number of required copies including the original form, which must be sent to the Statistical and Data Center.  
No         copies are required for forms submitted through SEDES.  Additionally, forms submitted through SEDES 
should not be sent through postal mail or fax. 
**At least one representative stained slide (or slides) documenting the primary invasive endometrial tumor, cell 
type, and histologic grade. At least one stained slide will be required, along with the Form F and pathology report 
for the recurrent disease in the pelvis. (10/18/2010) 
  ***Not required for Regimen I. 
****Only one T form is required for Regimen I subsequent to completing radiation therapy. 
 
This study utilizes the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 
v3.0) for defining and grading adverse events to be reported on GOG case report forms. A GOG 
CTCAE v3.0 Manual is available on the GOG member web site (http://www.gog.org under 
MANUALS) and can be mailed to the institution registering a patient to this study if requested.  
(5/23/2011) 
 
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. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 56 - 
11.0 
STATISTICAL CONSIDERATIONS   
 
11.1 
Study design overview and registration:  
Chemotherapy consisting of the combination of doxorubicin, cisplatin, and 
paclitaxel (TAP) is a standard treatment in the GOG for women with advanced or 
recurrent measurable endometrial cancer in which surgery and/or radiation are no 
longer thought to be curative.  Pelvic radiation following initial surgery is being 
used less frequently when disease is caught at an early stage.  Subsequently 
investigators have noticed a growing number of patients with isolated vaginal or 
pelvic recurrences.  Pelvic radiation is commonly given at recurrence and thought 
to be curative in a subset of these patients, however, data on efficacy of therapy 
for such patients are very limited; most of which are from retrospective studies.  
This screening trial will allow evaluation of the experimental arm given the lack 
of historical control data available.  Additionally, evaluation of prognostic factors 
such as tumor size, site, and histology will be possible.  Furthermore, these data 
will help to determine the feasibility of future studies in this population of 
patients. 
 
This study is a randomized Phase II screening clinical trial.32 This design will 
provide a preliminary assessment of the direct but non-definitive screening 
comparison of an intermediate endpoint between two therapeutic regimens: pelvic 
irradiation with or without weekly cisplatin.  All patients on this study will be 
registered and randomized centrally at the GOG Statistical and Data Center.  Prior 
to registration, eligibility will be reviewed via Fast Fact Sheet verification.  The 
sequence of treatment assignments will be concealed from institutions and 
patients until registration with verification of eligibility.  Randomization with 
equal probabilities to the two treatment regimens will be carried out following 
study registration.  All reports will include a complete accounting of all patients 
registered to this protocol. 
 
11.2 
Data collection: 
The principal parameters to be collected, analyzed, and reported to determine the 
relative therapeutic effect of the two treatment regimens are: 
 
11.21 Outcome Variables:  
Primary: Duration of progression-free survival  
Secondary: Duration of overall survival 
 
11.22 Tumor characteristics:  site of measurable disease (vaginal, central pelvic), 
tumor size as measured by the maximum dimension of the tumor, 
histological cell type, tumor grade and the presence of lymph-vascular 
space involvement of the original tumor at the time of  initial 
hysterectomy. 
 
11.23 Host characteristics:  age at entry, performance status, and race. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 57 - 
11.24 Adverse effects:  frequency and severity of adverse effects graded by 
CTCAE Version 3.0. 
 
11.25 Treatment:  total dose of radiation received (external beam and 
brachytherapy); the number of cycles of protocol directed therapy 
administered; for those not completing study therapy, the reason for not 
completing the assigned treatment 
 
11.3 
Accrual:  
The Gynecologic Oncology Group has not previously prospectively studied this 
population.  The anticipated annual accrual is 40 patients.  Accrual will be 
monitored on a quarterly basis.  If the average accrual rate is 20 patients per year 
or less at the end of 2 years, the feasibility of this study will be reassessed.  If the 
average annual accrual rate exceeds 60 patients at two years, then consideration 
for converting to a Phase III study will be given.  This decision will be made only 
on the basis of accrual and the sample size, Type I and II errors, and error 
spending functions will be modified to that which is appropriate for a Phase III 
study. 
 
Revision # 11:  Total accrual as of March 21, 2012 was 48 out of a projected 164 
assuming an accrual rate of 40 patients per year.  Annual accrual in 2011 was 15.  
In order to increase accrual several changes to this protocol are incorporated into 
this revision: 
 A change in eligibility that favors a lower risk patient population – 
patients with completely resected vaginal metastasis are now eligible 
 Use of IMRT for the entire radiation therapy prescription rather than just 
for the boost 
 
Accrual scenarios are presented in a table below. (05/14/2012) 
 
11.4 
Hypotheses and sample size:   
 
Primary Hypothesis:  This screening study will evaluate an intermediate endpoint 
as a preliminary indication of activity; progression-free survival.  The primary 
hypothesis of interest is “Is pelvic radiation with concurrent cisplatin active 
relative to pelvic radiation alone with respect to progression-free survival in 
patients with recurrent endometrial carcinoma limited to the pelvis and vagina?”  
The design of this study will provide preliminary evidence of efficacy with regard 
to progression-free survival.  The type I error level will be set at 0.10 (one tail) 
which allows for a higher false positive rate than for a usual randomized study 
design.  Since this rate is higher and an intermediate endpoint is chosen, the 
comparative results will be considered preliminary and in the event of a positive 
trial, a full-sized Phase III trial will be necessary to provide a definitive, more 
precise estimate of the treatment effect.  However, if the resulting p-value is less 
than 0.005, similar to that used for Phase III interim analysis, attention will be 
given to estimate the effect with respect to overall survival.  If the estimated effect 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 58 - 
size is similar to that seen in PFS, then it may be regarded as compelling.  In this 
event, the ability to conduct a Phase III trial may be severely limited. 
 
Background information:  Four recent studies provide estimates of 5 year overall 
survival among patients treated with radiation for vaginal recurrence of 
endometrial adenocarcinoma. 7,6, 27,29  These estimates are 0.75, 0.65, 0.55 and 
0.43.  The average of these estimates, weighted by the number of deaths reported 
in each study, is 0.52.  Assuming an exponential failure time distribution, the 
constant monthly hazard estimate is then –ln(0.52)/60=0.011.  Under the 
assumption that the hazard of progression or death is 1.5 times that of survival, 
then the estimate of the monthly hazard of progression or death is 
0.011*1.5=0.0165; translating into a median time to progression or death of 42 
months.  Similarly, the estimate of median overall survival among patients treated 
with radiation for pelvic recurrence of endometrial adenocarcinoma is 8 months.7   
 
Sample Size:  It is anticipated that 75% of patients registered to this study will 
have a recurrence limited to the vagina.  Among those with a vaginal recurrence, 
the median time to progression or death is assumed to be 42 months in the control 
arm.  Additionally, among those with a recurrence that is not isolated to the 
vagina (25% of patients registered), the median time to progression or death is 
assumed to be 8 months.  The relative decrease in the progression/death hazard of 
0.645 translates into an increase in median progression-free survival to 65.7 
months for vaginal recurrences and 12.5 for extra-vaginal recurrences.  This 
difference requires observing at least 94 failures to provide 80% statistical power 
when type I error is limited to 0.10 (one tail test). .33  A proportional hazards 
model will be used to assess the equality of hazard rates between the two 
regimens.  All eligible patients will be included in the analysis, regardless of the 
amount of study treatment received.  The analysis will be stratified by initial 
performance status and type of recurrence at entry (vaginal only vs. all others).  
Potential confounders including tumor size, tumor histology (serous/clear cell v 
all others), age, race and tumor grade, will be considered in an exploratory model. 
 
Revision # 11:  Patients with surgically removed vaginal recurrences are thought 
to be at lower or similar risk of progression on average than similar patients with 
vaginal recurrences who fit the eligibility criteria prior to this revision.  Assuming 
the hazard rates from the original statistical design but shifting the percentage of 
vaginal only recurrences to 100% or 85% from 75%, accrual and study durations 
are estimated under different accrual rate increase scenarios.  The current accrual 
duration assumed for this table is 50 months. 
 
Proportion 
with vaginal 
recurrence* 
Annual 
accrual 
rate 
Total accrual 
duration in 
months  
(sample size) 
Additional 
follow-up 
(months) 
Overall 
study 
duration 
(years) 
85% 
24 
102 (154) 
8 
9.2  
85% 
36 
84 (152) 
18 
8.5  

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 59 - 
85% 
48 
76 (154) 
20 
8.0  
100% 
32.4 
90 (153) 
24 
9.5 
*Following revision #11 
 
Secondary Hypotheses:  Overall survival and identification of prognostic factors 
with respect to PFS and overall survival.   
 
Overall survival (OS) will be analyzed as a secondary endpoint.  This endpoint is 
not expected to have sufficient power for a definitive test and will therefore be 
treated as supportive evidence.  All eligible patients will be included in the intent-
to-treat analysis.  The final analysis will be stratified by performance status and 
type of recurrence at entry (vaginal only vs. all others).  Other potential 
confounders will be assessed.   
 
This study will investigate the prognostic significance of tumor size, tumor 
location (vaginal only vs. all others) and histology in patients treated with 
radiation with or without cisplatin.  Additionally, age, race, and tumor grade will 
be evaluated as prognostic factors.  These analyses will help to define the 
appropriate population with sufficient risk for future studies involving therapy 
that is more aggressive.  A proportional hazards model adjusted for performance 
status and treatment will be used to explore the relationship between these 
variables and PFS or survival.   
 
Design assumptions:  Assumptions made to determine sample size will be 
checked after two years of accrual and prior to the planned time of closing the 
study to patient entry.  This will not involve a comparison of treatment arms but 
will be based upon aggregated data.   
 
Revision #11:  The accrual rate for this study has been monitored for several 
years.  In response to an initial slow accrual rate, this study was added to the 
CTSU menu and endorsed by RTOG.  Changes to the eligibility and flexibility in 
the radiation therapy prescription plan are now made to increase accrual beyond 
its current rate. (05/14/2012) 
 
11.5 
Study Duration:  
 
The planned sample size is 164 eligible patients.  It is anticipated that this study 
will require approximately 49 months of accrual assuming a uniform accrual rate 
of 40 patients per year.  It is estimated that twenty months of post accrual follow-
up will be necessary to observe the minimum number of failures required for the 
final primary analysis.  To avoid the small loss in power due to the interim futility 
analysis, consideration will be given to extension of follow-up, if necessary, to 
observe five additional failures prior to the final analysis. 
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 60 - 
11.6 
Interim Analyses: 
 
There will be one planned interim futility analysis of progression-free survival 
data.  The planned interim analysis will occur when approximately 60 failures 
have been reported.  If the observed rate of recurrence or death, stratified by 
performance status and type of recurrence at entry, of the experimental arm is 
greater than that of the control arm, then accrual termination will be considered (if 
still active) with a conclusion that an advantage for the experimental regimen has 
not been established.  This will result in a small loss in power for the current 
study, roughly, 0.005.34  
 
 
 
Other factors to be assessed at the time of interim analysis will include frequency 
and severity of adverse effects, the frequency of treatment termination due to 
toxicity, the OS relative hazard estimate, and potential confounders.   
 
The results of interim analyses are scheduled to be reviewed by the GOG Data 
Safety and Monitoring Board (DSMB) at its semi-annual meetings. This 
committee meets in January and July each year. The precise dates for these 
meetings are set more than one year in advance by individuals who have no 
knowledge of efficacy results.  Approximately eight weeks prior to each of these 
meetings, the database is locked in order to prepare a progress report. If the 
prerequisite number of events has been attained, an interim analysis is also 
prepared and presented to the DMC at their next scheduled meeting. The decision 
to terminate accrual to any particular regimen includes consideration of toxicities, 
treatment compliance, overall survival and results from external studies. 
Additionally, the GOG Safety Review Committee (SRC) reviews accumulating 
summaries of toxicities and all serious adverse event (SAE) reports on an ongoing 
basis (not efficacy results). This committee also reviews those deaths in which the 
study treatment may have been a contributing cause. The SRC reports to the DMC 
and may recommend study amendments pertaining to patient safety. (05/14/2012) 
 
11.7 
Anticipated Gender and Minority Inclusion:  
 
This study restricts entry to women by nature of the site of disease.  The table 
below lists the projected percentage of patients by racial/ethnic subgroup.  Prior 
GOG studies of similar populations support no differences in the intervention 
effect between racial/ethnic subgroups.  Therefore, the study design does not 
involve race.  However, subsets defined by white and non-white will be analyzed 
in this study to investigate this important question with the current therapies.       
 
    0.1% 
American Indian, Alaskan Native 
    1.7% 
Asian 
  14.6% 
Black 
    2.7% 
Hispanic 
  80.9% 
White 
100.0% 
Total 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 61 - 
 
  
12.0 
BIBLIOGRAPHY  
 
1.  
American Cancer Society.  Cancer Facts and Figures,  pg 4, 2006. 
 
2. 
Keys HM, Roberts JA, Brunetto VL, et al. A Phase III trial of surgery with or without 
adjunctive external pelvic radiation therapy in intermediate risk endometrial 
adenocarcinoma: A Gynecologic Oncology Group Study.  Gynecol Oncol. 744-751, 
2004. 
 
3. 
Creutzberg CL, Van Putten WLJ, Koper PCM, et al. For the PORTEC Study Group: 
Surgery and postoperative radiotherapy versus surgery alone for patients with stage-I 
endometrial carcinoma: Multicentre randomised trial.  Lancet. 355:1404-1411, 2000. 
 
4. 
Aalders J, Abeler V, Kolstadt P, et al. Postoperative external irradiation and prognostic 
parameters in stage I endometrial carcinoma: clinical and histopathological study of 540 
patients.  Obstet Gynecol. 56: 419-426, 1980. 
 
5. 
Randall ME, Filiaci VL, Muss H, et al. Randomized Phase III trial of whole abdominal 
irradiation versus Doxorubicin and Cisplatin chemotherapy in advanced endometrial 
carcinoma: A Gynecologic Oncology Group Study.  J Clin Oncol. 24:36-44, 2006. 
 
6. 
Ackerman I, Malone S, Thomas G, et al. Endometrial carcinoma- relative effectiveness of 
adjuvant irradiation vs. therapy reserved for salvage.  Gynecol Oncol. 60:177-183, 1996. 
 
7. 
Creutzberg CL, van Putten WLJ, Koper PC, et al. For the PORTEC Study Group: 
Survival after relapse in patients with endometrial cancer.  Results from a Randomized 
Trial. Gynecol  
Oncol.  89:201-209, 2003.  
 
8. 
Thigpen JT, Buschbaum HJ, Mangan C, et al. Phase II trial of adriamycin in the 
treatment of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology 
Group study.  Cancer  Treat Rep. 63:21-27, 1979. 
 
9. 
Horton J, Begg CB, Arseneault J, et al. Comparison of Adriamycin with 
cyclophsophamide in  patients with advanced endometrial cancer.  Cancer Treat Rep.  
62:159-161, 1978. 
 
10. 
Deppe G, Cohen CJ, Bruckner HW, et al. Treatment of advanced endometrial 
adenocarcinoma with cis-dichlorodiammine platinum (II) after intensive prior therapy.  
Gynecol Oncol. 10:51-54, 1980. 
 
11. 
Seski JC, Edwards CL, Herson J et al. Cisplatin chemotherapy for disseminated 
endometrial cancer.  Obstet Gynecol  59:225-228, 1982. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 62 - 
12. 
Thigpen JT, Blessing JA, Homesley H et al. Phase II trial of cisplatin as first-line 
chemotherapy in patients with advanced or recurrent endometrial carcinoma: A 
Gynecologic Oncology Group study.  Gynecol Oncol. 33:68-70, 1989. 
 
13. 
Thigpen JT, Blessing J, Homesley H et al. Phase III trial of doxorubicin +/- cisplatin in 
advanced and recurrent endometrial carcinoma: A Gynecologic Oncology Group Study.  
Proc  Am Soc Clin Oncol. 12:261, 1993 (Abstract #830). 
 
14. 
Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of Doxorubicin with or 
without cisplatin in advanced endometrial carcinoma: A Gynecologic Oncology Group 
Study.  J Clin  Oncol. 22: 3902-3908, 2004. 
 
15. 
Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of Doxorubicin plus Cisplatin 
with or without Paclitaxel plus Filgrastim in advanced endometrial carcinoma: A 
Gynecologic  Oncology Group Study.  J Clin Oncol. 22: 2159-2166, 2004. 
 
16. 
Long HJ, et al. Phase II evaluation of carboplatin in advanced endometrial carcinoma.  J 
Natl Cancer Inst. 80:276-278, 1988. 
 
17. 
Keys HM, Bundy BN, Stehman FB, et al.  Cisplatin, radiation and adjuvant hysterectomy 
 
compared with radiation and adjuvant hysterectomy for bulky stage IB cervical 
carcinoma.  N Engl J Med. 340:1154-1161, 1999. 
 
18. 
Morris M, Eifel PJ, Lu J, et al. Pelvic irradiation with concurrent chemotherapy 
compared with pelvic and para-aortic radiation for the high-risk cervical cancer.  New 
Engl J Med. 340:1137-1143, 1999. 
 
19. 
Rose PG, Bundy BN, Watkins EB et al. Concurrent cisplatin-based radiotherapy and 
chemotherapy for locally advanced cervical cancer.  N Engl J Med. 340: 1144-1153, 
1999. 
 
20. 
Whitney CW, Sause W, Bundy BN et al. Randomized comparison of fluorouracil plus 
cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA 
carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology 
Group and Southwest Oncology Group Study.  J Clin Oncol. 17:1339-1348, 1999. 
 
21. 
Reisinger SA, Asbury R, Liao SY, Homesley HD.  A phase I study of weekly cisplatin 
and whole abdominal radiation for the treatment of stage III and IV endometrial 
carcinoma:  A Gynecologic Oncology Group pilot study.  Gynecol Oncol. 63:299-303, 
1996. 
 
22. 
Soper JT, Reisinger SA, Ashbury R, Jones E, Clarke-Pearson DL.  Feasibility study of 
concurrent weekly cisplatin and whole abdominopelvic irradiation followed by 
doxorubicin/cisplatin chemotherapy for advanced stage endometrial carcinoma:  A 
Gynecologic Oncology Group trial.  Gynecol Oncol. 95:95-100, 2004. 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 63 - 
23. 
Jereczek-Fossa B, Badzio A, Jassem J.  Recurrent endometrial cancer after surgery alone: 
results of salvage radiotherapy.  Int J Radiat Oncol Biol Phys 48:405-413, 2000. 
 
24. 
Jhingran A, Burke TW,  Eifel PJ.  Definitive radiotherapy for patients with isolated 
vaginal recurrence of endometrial carcinoma after hysterectomy.  Int J Radiat Oncology 
Biol Phys.  
56:1366-1372, 2003. 
 
25. 
Hart KB, Han I, Shamsa F, et al.  Radiation therapy for endometrial cancer in patients 
treated  for postoperative recurrence.  Int J Radiat Oncol Biol Phys. 41: 7-11, 1998. 
 
26. 
Nag S, Yacoub S, Copeland L, Fowler J.  Interstitial brachytherapy for salvage treatment 
of  
vaginal recurrences in previously unirradiated endometrial cancer patients.  Int J 
Radiat Oncol  Biol Phys.  54:1153-1159, 2002. 
 
27.  
Lin L, Grigby P, Powell M et al. Definitive radiotherapy in the management of isolated 
vaginal recurrences of endometrial cancer. Int J Rad Oncol Biol Phys. 63: 500-504, 2005. 
 
28.  
Petignat P, Jolicoeur M, Alobaid A, Drouin P et al: Salvage treatment with high-dose rate 
brachytherapy for isolated vaginal endometrial cancer recurrence. Gynecol Oncol 2006; 
445-449. 
 
29 
Huh WK, Straughn JM Jr, Mariani A, Podratz KC, Havrilesky LJ, Alvarez-Secord A, 
Gold MA, McMeekin DS, Modesitt S, Cooper AL, Powell MA, Mutch DG, Nag S, 
Alvarez RD, Cohn DE.  Salvage of isolated vaginal recurrences in women with surgical 
stage I endometrial cancer: a multiinstitutional experience.  Int J Gynecol Cancer, 2007, 
Feb 14 [Epub].   
 
 
 
30.  
Mundt AJ, McBride R, Rotmensch J, et al. Significant pelvic recurrence in high-risk 
pathologic stage I-IV endometrial carcinoma patients after adjuvant chemotherapy alone: 
implications for adjuvant radiation therapy.  Int J Radiat Oncol Biol Phys. 50: 1145-1153, 
2001. 
 
31. 
Dittmer PH, Randall ME: A technique for inguinal node boosts using photon fields 
defined by asymmetric collimators jaws.  Radiother Oncol. 59:61-64, 2001. 
 
32. 
Rubinstein LV, Korn EL, et al. Design issues of randomized phase II trials and a proposal 
for phase II screening trials.  J Clin Oncol. 23 (28): 7199-206, 2005. 
 
33. 
Schoenfeld DA: Sample size formula for the proportional hazards regression model.  
Biometrics. 39:499-503, 1983. 
 
34. 
Wieand S, Schroeder G, et al. Stopping when the experimental regimen does not appear 
to help.  Stat Med. 13: 1453-8, 1994. 
  
 
 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 64 - 
APPENDIX I 
 
CLINICAL STAGING - CARCINOMA OF THE CORPUS UTERI 
FIGO CLASSIFICATION 
(1988) 
 
STAGE O: 
Carcinoma in situ.  Histologic findings suspicious of malignancy. 
 
 
 
(Cases of Stage 0 should not be included in any therapeutic statistics.) 
 
STAGE I: 
The carcinoma is confined to the corpus. 
 
 
 
STAGE IA: 
The length of the uterine cavity is 8 cm or less. 
 
 
STAGE IB: 
The length of the uterine cavity is more than 8 cm. 
 
 
 
The Stage I cases should be sub-grouped with regard to the histological type of 
the adenocarcinoma as follows: 
 
 
 
G1 
- 
Highly differentiated adenomatous carcinoma. 
 
 
G2 
- 
Differentiated adenomatous carcinoma with partly solid areas. 
 
 
G3 
- 
Predominantly solid or entirely undifferentiated carcinoma. 
 
STAGE II: 
The carcinoma has involved the corpus and the cervix. 
 
STAGE III: 
The carcinoma has extended outside the uterus but not outside the true pelvis. 
 
STAGE IV: 
The carcinoma has extended outside the true pelvis or has obviously involved the 
mucosa of the bladder or rectum.  A bullous edema as such, does not permit a case to be allotted 
to Stage IV. 
 
STAGE 
IA G123: 
 
Tumor limited to endometrium. 
 
 
 
IB G123: 
 
Invasion to < 1/2 myometrium. 
 
 
 
IC G123: 
 
Invasion > 1/2 myometrium. 
 
STAGE  
IIA G123: 
 
Endocervical glandular involvement only. 
 
 
 
IIB G123: 
 
Cervical stromal invasion. 
 
STAGE  
IIIA G123: 
Tumor invades serosa and/or adnexae and/or positive peritoneal 
cytology. 
 
STAGE  
IIIB G123: 
 
Vaginal metastases. 
 
 
 
IIIC G123: 
Metastases to pelvic and/or para-aortic lymph nodes. 
 
STAGE  
IVA G123: 
Tumor invasion bladder and/or bowel mucosa. 
 
 
 
IVB:  
 
Distant metastases including intra-abdominal and/or 
inguinal lymph node. 

NCI Protocol #: GOG-0238 
Version Date: 05/28/2019 
- 65 - 
 
CLINICAL STAGING - CARCINOMA OF THE CORPUS UTERI (con't) 
FIGO CLASSIFICATION 
(1988) 
 
 
Histopathology -- Degree of Differentiation 
 
Cases of carcinoma of the corpus should be grouped with regard to the degree of differentiation 
of the adenocarcinoma as follows: 
 
G1 = 5% or less of a non-squamous or non-morular solid growth pattern. 
G2 = 6-50% of a non-squamous or non-morular solid growth pattern. 
G3 = More than 50% of a non-squamous or non-morular solid growth pattern. 
 
Notes on Pathological Grading 
 
(1) 
Notable nuclear atypia, inappropriate for the architectural grade, raises the grade of a 
grade I or grade II tumor by 1. 
 
(2) 
In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, 
nuclear grading takes precedence. 
 
(3) 
Adenocarcinomas with squamous differentiation are graded according to the nuclear grade 
of the glandular component. 
 
Rules Related to Staging 
 
(1) 
Since corpus cancer is now surgically staged, procedures previously used for 
determination of stages are no longer applicable, such as the finding of fractional D&C to 
differentiate between stage I and stage II. 
 
(2) 
It is appreciated that there may be a small number of patients with corpus cancer who will 
be treated primarily with radiation therapy.  If that is the case, the clinical staging adopted 
by FIGO in 1971 would still apply but designation of that staging system would be noted. 
 
(3) 
Ideally, width of the myometrium should be measured along with the width of tumor 
invasion.