A Phase II Trial Evaluating Cisplatin (NSC #119875) and Gemcitabine (NSC #613327) Concurrent With Intensity-Modulated Radiation Therapy (IMRT) in the Treatment of Locally Advanced Squamous Cell Carcinoma of the Vulva (NCT #01595061)
Phase: PHASE2
Conditions: Stage III Vulvar Cancer AJCC v7, Stage IIIA Vulvar Cancer AJCC v7, Stage IIIB Vulvar Cancer AJCC v7, Stage IIIC Vulvar Cancer AJCC v7, Stage IVA Vulvar Cancer AJCC v7, Vulvar Squamous Cell Carcinoma
Sponsor: Gynecologic Oncology Group

 
i 
TO: 
 
ALL PRINCIPAL INVESTIGATORS/NURSES/DATA MANAGERS 
 
FROM: 
MEG COLAHAN 
 
 
 
PROTOCOL SECTION 
 
DATE: 
AUGUST 15, 2016 
 
RE: 
 
GOG-0279 – AMENDMENT #4 
 
Protocol Title:  “A PHASE II TRIAL EVALUATING CISPLATIN (NSC #119875) AND 
GEMCITABINE (NSC # 613327) CONCURRENT WITH INTENSITY-MODULATED RADIATION 
THERAPY (IMRT) IN THE TREATMENT OF LOCALLY ADVANCED SQUAMOUS CELL 
CARCINOMA OF THE VULVA  NCI Version Date: 07/21/2016 
 
Study Chair: Neil S. Horowitz, M.D.; (617) 724-8843; E-mail: nhorowitz@partners.org  
 
IRB Recommendations 
 
(  ) No review required 
(X) Expedited review; however, site IRB requirements take precedence 
(  ) Full board review recommended because there have been changes to the 
eligibility and/or informed consent 
 
Please direct questions about the recommended level of IRB review and/or re-consenting patients to 
your local IRB. The local IRB will make this determination. If your local IRB does not agree with the 
GOG’s recommended level of review, please document the IRB’s decision and the rationale for the 
decision in your study files. 
 
The following changes have been made and become effective August 15, 2016: 
 
 
SUMMARY OF CHANGES 
 
For Protocol Amendment #4 to: GOG-0279 
 
NCI Protocol #: GOG-0279 
Local Protocol #: GOG-0279 
 
NCI Version Date: 07/21/2016 
Protocol Date: 08/15/2016 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
i 
 
# 
Section 
Page(s) 
Change 
1 
Title Pages 
1 and 2 
• NCI Version Date is now 07/21/2016 
• Includes Amendments #1-4 
• to reflect date of revision. 
 
2 
Schema 
3 
Consent should be obtained prior to surgery; registration should 
occur within 2 weeks of surgery. 
3 
4.3511 
15 
In the first sentence, “64 Gy in 34 fractions” has been corrected to 
“64 Gy in 32 fractions.” 
4 
4.39 
20, 21 
The second sentence now reads:  “It is anticipated that radiation 
therapy will start as soon as clinically feasible at the discretion of 
the treating physician, but within 6 weeks of enrollment.” 
5 
5.4 
28, 29 
• “Although it is preferable to have patients registered for 
the trial prior to the lymph node surgical evaluation, 
patients may be registered/enrolled postoperatively.  If 
patients do not register/enroll until postoperative from the 
groin node assessment, the treating physician should 
determine if patients meet eligibility requirements 
(requirement 3.13 can be determined as part of standard 
practice in preoperative lab work) and confirm that they 
and the patient agree the treatment protocol is appropriate 
and acceptable therapy” has been added to the first 
paragraph. 
• “As time to recover from a sentinel lymph node biopsy is 
different from an inguinal femoral dissection, 
commencement of radiation post-operatively will be at the 
discretion of the treatment physician, however, patients 
must be registered/enrolled in the trial within 2 weeks of 
surgery and IMRT must start no later than 6 weeks after 
surgery” has been added to the “Radiation” paragraph. 
• The second to the last paragraph now reads:  
“Chemotherapy should start on the same day as the start of 
radiation.  There is no required timeframe for 
chemotherapy (i.e., before or after radiation) on the day of 
radiation.” 
6 
6.0 
30 
• A “Dose Delay” table has been added for clarity. 
• The dose reduction table has been labeled, “Dose 
Modifications.” 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
ii 
# 
Section 
Page(s) 
Change 
7 
7.1 
36 
• The list of blood chemistries has been replaced with 
“Clinical Chemistry” and a reference to note 10 which 
lists the required tests has been added to the Pre-treatment 
column. 
• “(+/- 10 day window)” has been added to the last Post-
Treatment column heading. 
8 
8.21 
39 
This section now reads:  “Overall Survival – defined as the 
observed length of life from start of protocol therapy to death or, 
for living patients, the date of last contact.” 
9 
8.22 
39 
This section now reads:  “Progression-free interval – defined as 
the date from start of protocol therapy to date of reappearance of 
disease or date of last contact.” 
10 
Appendix II 
58 
The appendix has been revised to reflect the most current 
version:  the last bullet has been deleted. 
 
IC 
 
Additional changes have been made to the IC. 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
- 1 - 
PROTOCOL GOG-0279 
A PHASE II TRIAL EVALUATING CISPLATIN (NSC #119875) AND GEMCITABINE (NSC # 
613327) CONCURRENT WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) IN 
THE TREATMENT OF LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE 
VULVA (NCT #01595061) (04/21/2014) 
 
NCI Version Date: 07/21/2016 
 
Includes Amendments #1 -4 
POINTS: 
PER CAPITA - 20 
MEMBERSHIP – 3 
Lead Organization: NRG / NRG Oncology (04/21/2014) 
. 
STUDY CHAIR 
STUDY CO-CHAIR(S) 
NEIL S. HOROWITZ, MD 
IVY PETERSEN, M.D. 
DANA FARBERS PARTNERS CANCER CARE See GOG Website Directory 
BRIGHAM AND WOMEN’S HOSPITAL 
75 FRANCIS STREET 
DON DIZON, M.D. (08/26/2013) 
BOSTON, MA  02115 
MASSACHUSETTS GENERAL HOSPITAL 
(617) 724-8843 
GYN  ONCOLOGY 
FAX:  (617) 724-5124 
55 FRUIT STREET 
Email: nhorowitz@partners.org  
YAWKEY 9E 
 
 
BOSTON, MA 02114 
NURSE CONTACT 
(617) 734-4800 
JILLIAN KNAZEK, RN 
Email: ddizon@partners.org  
UNIVERSITY HOSPITALS CASE MEDICAL CTR 
DEPT GYN/ONC 
 
11100 EUCLID AVE, ROOM MAC-7128 
PATHOLOGIST 
CLEVELAND, OH 44106 
HELEN MICHAEL, M.D. 
(216) 844-8787 
See GOG Website Directory 
FAX: (216) 844-8596 
 
 
 
Email: jillian.knazek@UHhospitals.org 
STATISTICIAN 
 
SHAMSHAD ALI, MS 
 
See GOG Website Directory 
 
 
 
 
 
OPEN TO PATIENT ENTRY JULY 2, 2012 
REVISED NOVEMBER 13, 2012 
 
EN TO PATIENT ENTRY JULY 2, 2012; REVISED NOVEMBER 13, 2012;  
REVISED AUGUST 26, 2013; REVISED APRIL 21, 2014;  
TEMPORARILY CLOSED TO PATIENT ENTRY JUNE 15, 2015; REVISED AUGUST 15, 2016 
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. 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
- 1 - 
 
PROTOCOL GOG-0279 
A PHASE II TRIAL EVALUATING CISPLATIN (NSC #119875) AND GEMCITABINE (NSC # 613327) 
CONCURRENT WITH INTENSITY-MODULATED RADIATION THERAPY (IMRT) IN THE 
TREATMENT OF LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE VULVA 
NCI Version Date:  07/21/2016 
CONTACT INFORMATION (04/21/2014) 
To submit site registration 
documents: 
For patient enrollments: 
Submit study data 
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.or
g (for submitting regulatory 
documents only) 
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_S
YSTEM/ 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 
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.  
For detailed information on the regulatory and monitoring procedures for CTSU sites please review the 
CTSU Regulatory and Monitoring Procedures policy located on the CTSU members’ website   
https://www.ctsu.org > education and resources tab > CTSU Operations Information >CTSU Regulatory and 
Monitoring Policy  
The CTSU Website is located at https://www.ctsu.org. 
OPEN TO PATIENT ENTRY JULY 2, 2012; REVISED NOVEMBER 13, 2012; REVISED 
AUGUST 26, 2013; REVISED APRIL 21, 2014; TEMPORARILY CLOSED TO PATIENT ENTRY 
JUNE 15, 2015; REVISED AUGUST 15, 2016 

NCI Protocol #: GOG-0279  
Version Date: 07/21/2016 
- 2 - 
SCHEMA 
 
 
 
 
 
 
 
 
 
Locally advanced squamous cell carcinoma of the vulva, T2 or T3 primary tumors 
(N0-3, M0) not amenable to surgical resection by standard radical vulvectomy 
Resectable Lymph Nodes   
Patients will undergo a pre-treatment inguinal-femoral lymph 
node dissection or sentinel lymph node biopsy 
No radiation vs. 45 Gy to groin(s) 
and low pelvis; 64 Gy to vulva 
 
Gemcitabine 50 mg/m2 + 
Cisplatin 40mg/m2 administered 
weekly throughout radiation 
therapy 
LN (-) 
50 Gy to groin(s) and low 
pelvis with groin boost to 60 Gy 
to involved sides if 
3 LN (+) or 
extra capsular extension or 
close/positive margin 
 
64 Gy to vulva 
 
Gemcitabine 50 mg/m2 + 
Cisplatin 40mg/m2 administered 
weekly throughout radiation 
therapy 
Unresectable Lymph Nodes 
Radiation 64 Gy to 
vulva and unresectable 
groin(s) and 50 Gy to 
non-malignant groin and 
low pelvis 
 
Gemcitabine 50 mg/m2 
+ Cisplatin 40mg/m2 
administered weekly 
throughout radiation 
therapy 
 Clinical/Radiographic assessment 6-8 weeks after 
chemoradiation 
FNA of clinical or radiographic 
residual 6-8 weeks after 
chemoradiation 
Target excision of (+) LNs 
Complete Clinical Response 
 No Complete Clinical 
Response 
Local, core biopsies of 
tumor bed to confirm 
complete pathologic 
 Surgical resection of residual 
disease or additional 
chemoradiation 
LN (+)  
Patient registration within 2 weeks of surgery  See Section 5.4 (08/15/2016) 
CONSENT prior to surgery (08/15/2016) 

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- 3 - 
 
 
TABLE OF CONTENTS 
PAGE 
SCHEMA 
- 2 - 
1.0 
OBJECTIVES 
- 5 - 
1.1 Primary Objectives 
- 5 - 
1.2 Secondary Objectives 
- 5 - 
2.0 
BACKGROUND AND RATIONALE 
- 5 - 
2.1 Inclusion of Women and Minorities 
- 7 - 
3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS 
- 8 - 
3.1 Eligible Patients 
- 8 - 
3.2 Ineligible Patients 
- 8 - 
4.0 
STUDY MODALITIES 
- 10 - 
4.1 Cisplatin (Platinol®-AQ) (NSC #119875) 
- 10 - 
4.2 Gemcitabine, Gemzar® (NSC #613327) 
- 11 - 
4.3 Radiation Therapy 
- 13 - 
4.4 Pathology Requirements 
- 21 - 
5.0 
TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE (04/21/2014) - 23 - 
5.1 IROC HOUSTON (FORMERLY THE RADIOLOGICAL PHYSICS CENTER [RPC]) 
CREDENTIALING REQUIREMENTS (04/21/2014) 
- 23 - 
5.2 Registration Procedures (04/21/2014) 
- 24 - 
5.3 Patient Entry and Registration (04/21/2014) 
- 27 - 
5.4 Treatment Plan (  ) 
- 28 - 
6.0 
TREATMENT MODIFICATIONS (  ) 
- 30 - 
6.1  
Cisplatin Modifications (see Section 6.2 for Gemcitabine Modifications) 
- 30 - 
6.2 Gemcitabine Modifications 
- 33 - 
6.3  
Radiation Modifications: 
- 35 - 
7.0 
STUDY PARAMETERS 
- 36 - 
7.1 Observations and Tests (  ) 
- 36 - 
7.2 STAINED PATHOLOGY SLIDE REQUIREMENTS FOR CENTRAL REVIEW TO 
CONFIRM ELIGIBILITY (08/26/2013) 
- 37 - 
7.3 Translational Research 
- 38 - 
7.4 Quality of Life 
- 38 - 
8.0 
EVALUATION CRITERIA 
- 39 - 
8.1  
Objective Response 
- 39 - 
8.2 Other Objective Response 
- 39 - 
8.3 Subjective Response 
- 39 - 
8.4. 
Adverse Effects 
- 39 - 
9.0 
DURATION OF STUDY 
- 40 - 
9.1 Patients will continue on study until disease progression or adverse effects prohibit further 
treatment. The patient can refuse the study treatment at any time. 
- 40 - 
9.2 All patients will be treated (with completion of all required case report forms) through the 
duration of the protocol treatment, until disease progression while on protocol treatment, 
unacceptable toxicity, or study withdrawal. Patients will then be followed (with physical 
exams and histories) every three months for the first two years and then every six months 

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for the next three years. Patients will be monitored for delayed toxicity and survival for 
this 5-year period with Q forms submitted to the GOG Statistical and Data Center, unless 
consent is withdrawn. (08/26/2013) 
- 40 - 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES 
- 41 - 
10.1 
ADVERSE EVENT REPORTING FOR A COMMERCIAL AGENT (04/21/2014)- 41 - 
10.2  GOG DATA MANAGEMENT FORMS 
- 44 - 
11.0 
STATISTICAL CONSIDERATIONS 
- 46 - 
11.1 
Study Objectives 
- 46 - 
11.2 
Endpoints and Data Elements 
- 46 - 
11.3 
Accrual and Study Duration 
- 47 - 
11.4 
Study Design and Sample Size Justification. 
- 47 - 
11.5 
Analysis Plan 
- 50 - 
11.6 
Study Monitoring, Data Quality Control and Semi-annual Reports 
- 51 - 
11.7 
Planned Minority Inclusion 
- 53 - 
12.0 
BIBLIOGRAPHY 
- 54 - 
APPENDIX I 
- 56 - 
APPENDIX II 
- 58 - 
APPENDIX III 
- 59 - 
APPENDIX IV 
- 60 - 
APPENDIX V 
- 61 - 
 
 
 
 SUGGESTED PATIENT INFORMATION/INFORMED CONSENT 
 
 

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1.0 
OBJECTIVES  
 
1.1 
Primary Objectives 
 
 
1.11 
To determine the efficacy of cisplatin, gemcitabine, and Intensity-
Modulated Radiation Therapy (IMRT) in achieving a complete pathologic 
response when used for the primary treatment of locally-advanced 
squamous cell carcinoma of the vulva.  
 
1.2 
Secondary Objectives 
 
1.21 
To determine the efficacy of cisplatin, gemcitabine, and IMRT in 
achieving a complete clinical response when used for the primary 
treatment of locally-advanced squamous cell carcinoma of the vulva.  
 
1.22 
To determine the vulvar progression-free survival and groin progression-
free survival in women treated with cisplatin, gemcitabine and IMRT for 
locally advanced vulvar carcinoma.  
 
1.23 
To determine the toxicity and surgical morbidity of the combined modality 
approach of cisplatin, gemcitabine and IMRT followed by reduced-scope 
surgery for the treatment of locally-advanced vulvar carcinoma. 
 
2.0 
BACKGROUND AND RATIONALE 
 
Invasive vulvar cancer is an uncommon malignancy, representing 5% of gynecologic 
cancers. It is estimated that 3,900 new cases and 900 deaths will be reported in the United 
States for 2010 with the vast majority (90%) histologically identified as squamous cell 
carcinoma (SCC).1 The majority of patients present with early stage disease but for those 
with locally advanced vulvar cancer, disease management remains a challenge.  
Historically, exenterative procedures were necessary with anal, rectal, urethral or bladder 
involvement thus leading to significant physical and psychological morbidity.  Over the 
last several years the GOG has improved the outcomes for these women by using multi-
modality therapy of chemotherapy, radiation, and surgery.  Combining cisplatin and 5 FU 
with radiation in GOG-0101, 93% of patients with advanced primary tumors were 
rendered resectable, without having to sacrifice urinary and/or gastrointestinal 
continence.  Forty-six percent of patients had no clinical evidence of vulvar tumor 
following chemoradiation and 31% had no residual tumor on the pathologic specimen.2   
In this trial, the total radiation dose was purposefully less than what is typically used 
when radiation is the sole treatment and a split-course regimen was employed to diminish 
potential severe acute toxicity.   
 
Building upon its experience of treating cervical squamous cell carcinoma with cisplatin, 
the GOG initiated protocol GOG-0205 evaluating cisplatin 40 mg/m2 weekly concurrent 
to radiation therapy in advanced vulvar cancer.  This trial eliminated a specified treatment 

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break and delivered a higher dose of radiation (20% dose escalation as compared to 
GOG-0101).  There were 58 evaluable patients of whom 40 (69%) completed study 
treatment.  Complete clinical responses were seen in 37 patients (37/58, 64%).  Among 
the 37 patients who achieved a complete clinical response, 34 underwent surgical biopsy 
and 29 had confirmed complete pathologic responses, for an overall complete pathologic 
response rate of 50% (29/58) for all evaluable patients).3   
 
Since the initiation of GOG-0101 and GOG-0205, significant advances have been made 
in radiation techniques; more specifically, the use of Intensity-Modulated Radiation 
Therapy (IMRT).  Unlike traditional radiation utilizing external beam AP-PA fields, 
IMRT allows for more precise delivery of radiation to malignant tumors.  Using 3-D 
computed tomography (CT) images of the patient, in conjunction with computerized dose 
calculations, IMRT allows for higher radiation doses to be conformed to tumor shapes 
while minimizing the dose to surrounding normal critical structures.  Using this modality 
of radiotherapy results in higher radiation doses with reduced treatment toxicity. In a 
small study by Beriwal et al. 15 patients with vulvar cancer, 7 preoperatively and 8 post-
operative, were treated with IMRT.  Compared to traditional radiation, IMRT lead to a 
reduction in unnecessary dose to the bladder, rectum, and small bowel and a low 
incidence of severe toxicity.4  
Gemcitabine is a deoxycytidine analog anti-metabolite that is structurally related to 
cytosine arabinoside that inhibits DNA synthesis.  Gemcitabine leads to an accumulation 
of dFdCP which in turn inhibits DNA polymerase and results in chain termination and 
apoptosis.5, 6  Gemcitabine is a known radiosensitizer7,8 and has shown synergy with 
cisplatin.9,10  Although gemcitabine has not been used to treat vulvar cancer to date, its 
chemical and biologic properties, in addition to the short infusion and same-day 
administration, make it an attractive agent to combine with cisplatin for the treatment of 
women with locally advanced vulvar cancer. 
In a phase I trial, GOG-9912, the GOG evaluated whole pelvic radiation therapy with 
weekly concurrent cisplatin and gemcitabine for the treatment of cervical cancers. In this 
trial, patients received gemcitabine intravenously over 30 minutes followed by cisplatin.  
The maximum tolerated dose was gemcitabine 50 mg/m2 and cisplatin 40 mg/m2 with 
dose-limiting toxicities primarily being nausea, vomiting, diarrhea and hematologic.11 
Interestingly, when sequenced in reverse, cisplatin followed by gemcitabine, higher doses 
of gemcitabine have been administered with acceptable toxicity.12-14 Based on the 
experience with locally advanced cervical cancer, the combination of concurrent weekly 
cisplatin (40 mg/m2) and gemcitabine (125 mg/m2) with whole pelvic radiation has 
resulted in improved complete pathologic response, 77% v 55%, and an improved 
progression-free and overall survival.14, 15 
The purpose of this study therefore was to expand upon the success of study GOG-0205 
by adding gemcitabine and increasing the radiation dose using the most modern radiation 
techniques. 
 
 

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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 all women with locally-
advanced squamous cell carcinoma of the vulva treated by participating 
institutions. 
 
 

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3.0 
PATIENT ELIGIBILITY AND EXCLUSIONS  
 
3.1 
Eligible Patients  
 
3.11 
Patients with locally-advanced, previously untreated squamous cell 
carcinoma of the vulva. 
 
3.12 
Patients with T2 or T3 primary tumors (N0-3, M0) not amenable to 
surgical resection by standard radical vulvectomy. 
 
3.13 
Patients must have adequate: 
 
3.131 Bone marrow function: Absolute neutrophil count (ANC) greater 
than or equal to 1,500/mcl Platelets greater than or equal to 
100,000/mcl. (08/26/2013) 
 
3.132 Renal function: Creatinine ≤ 1.5 x institutional upper limit normal 
(ULN) or calculated creatinine clearance ≥ 60 ml/min.  
 
 
3.133 Hepatic function: Bilirubin ≤ 1.5 x ULN.  AST and ALT ≤ 3.0 x 
ULN and alkaline phosphatase ≤ 3.0 x ULN.   
 
3.14 
Patients judged capable of tolerating a radical course of chemoradiation 
therapy. 
 
3.15 
Patients must not be eligible for a higher priority GOG protocol, if one 
exists.  In general, this would refer to any active GOG Phase III protocol 
or Rare Tumor protocol for the same patient population. 
 
3.16 
Patients who have met the pre-entry requirements specified in Section 7.0. 
 
3.17 
Patients must have signed an approved informed consent and authorization 
permitting release of personal health information. 
 
3.18 
Patients must be 18 years or older. 
 
3.19 
Patients with a GOG Performance Status of 0, 1 or 2 
 
3.2 
Ineligible Patients 
 
3.21 
Patients with recurrent carcinoma of the vulva regardless of previous 
treatment. 
 
3.22 
Patients who have received prior pelvic radiation or cytotoxic 
chemotherapy. 
 

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3.23 
Patients with vulvar melanomas or sarcomas. 
 
3.24 
Patients with circumstances that will not permit completion of the study or 
the required follow-up. 
 
3.25 
Patients with evidence of active septicemia, severe infection, 
gastrointestinal bleeding or severe gastrointestinal symptoms requiring 
medical or surgical therapy. 
 
3.26 
Patients with a history of other invasive malignancies, with the exception 
of non-melanoma skin cancer, are excluded if there is any evidence of 
other malignancy being present within the last five years.  Patients are also 
excluded if their previous cancer treatment contraindicates this protocol 
therapy. 
 
 
 

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Version Date:  07/21/2016 
 
- 10 - 
4.0 
STUDY MODALITIES   
 
4.1 
Cisplatin (Platinol®-AQ) (NSC #119875) 
 
 
4.11 
Formulation:  Cisplatin is available as an aqueous solution in 50 mg and 
100 mg vials where each mL contains 1 mg of cisplatin and 9 mg of 
sodium chloride. 
 
4.12 
Preparation: Aluminum reacts with Platinol 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 Platinol. 
 
4.13 
Storage:  The aqueous solution should be stored at room temperature and 
protected from light.   
 
4.14 
Administration:  See Section 5.4 
 
4.15 
Adverse effects:  Leukopenia, thrombocytopenia, anemia nausea, 
vomiting, nephrotoxicity, ototoxicity, peripheral neuropathy, electrolyte 
imbalance, hypocalcemia, hypomagnesemia, aminoglycoside, ototoxicity, 
ocular toxicity and allergic reactions.  Infrequent: Cardiac abnormalities, 
anorexia, elevated SGOT, rash and alopecia. 
 
NOTE: Aminoglycoside antibiotics given before, with, or after cisplatin 
may potentiate renal toxicity and should be avoided whenever possible. 
 
Severe renal toxicity can be largely avoided by induction of a diuretic 
before, during and after treatment. 
 
Mild renal dysfunction is a common complication (10%) of chronic 
therapy and may require discontinuation of therapy if BUN > 30 mg/dl or 
creatinine > 2.0 mg/dl develop. 
 
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. 
 
Allergic reactions are rare.  If accompanied by respiratory symptoms, 
allergic reactions require discontinuation of treatment.  Patch or skin tests 
are recommended for patients with suspected allergy to cisplatin.  
Platinum desensitization protocols can be employed if it does not lead to 

NCI Protocol #: GOG-0279  
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- 11 - 
delayed radiation.  An emergency set for the treatment of allergic reactions 
should be available in the treatment area. 
 
Local necrosis and thrombophlebitis can be avoided by careful 
administration. 
 
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. 
 
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 be questioned about hearing loss.  
Patients with a history of hearing loss should be considered for pre-
treatment audiometry with follow up audimetry as clinically indicated.  It 
is recommended that patients be queried concerning hearing loss before 
each cycle of cisplatin. 
 
4.16 
Supplier:  Commercially available. Bristol-Myers Oncology 
 
*See FDA-approved package insert for a comprehensive list of adverse 
events associated with cisplatin.  
 
4.2 
Gemcitabine, Gemzar® (NSC #613327) 
 
 
4.21  Formulation: Gemcitabine HCl is a nucleoside analog that exhibits anti-
tumor activity.  
 
4.22 
Supplier/How Supplied: Gemcitabine HCl is commercially available from 
Eli Lilly and Co. Gemcitabine is supplied as a white lyophilized powder in 
sterile single use vials containing 200mg (10 ml) or 1000 mg (50 ml) of 
gemcitabine as the hydrochloride salt.  
 
4.23 
Stability/Storage:  Unopened vials of gemcitabine are stable until the 
expiration date indicated on the package when stored at controlled room 
temperature between 20 to 25°C (68 to 77° F).  
 
4.24 
Preparation:  To reconstitute, add 5 ml of 0.9% Sodium Chloride Injection 
to the 200 mg vials or 25 ml to the 1000 mg vial. Shake to dissolve. These 
dilutions each yield a gemcitabine concentration of 38 mg/ml which 
includes accounting for the displacement volume of the lyophilized 
powder. The total volume upon reconstitution will be 5.26 ml or 26.3 ml, 
respectively. Complete withdrawal of the contents will provide 200 mg or 

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1 g of gemcitabine, respectively. The appropriate amount of drug may be 
administered as prepared or further diluted with 0.9% Sodium Chloride 
Injection to concentrations as low as 0.1 mg/ml. The solution should be 
clear, colorless to slightly straw colored. Do not administer if discoloration 
or particulate matter is found. Once the drug has been reconstituted, it 
should be stored at controlled room temperature and used within 24 hours.  
 
4.25 
Administration: The mixed solution will be continuously infused over 30 
minutes (See Section 5.4). 
 
 
4.26 
Adverse effects: 
 
Hematologic: The following Grade 3 and 4 toxicities can be expected after 
single agent therapy with doses between 800 and 1250 mg/m2: neutropenia 
25%, leukopenia 9%, anemia 8%, and thrombocytopenia 5%. Infection 
occurred in 16% of patients; sepsis occurred in less than 1%. 17% of 
patients experienced hemorrhage of Grade 2 or less.  
Gastrointestinal:  Nausea and vomiting is frequent, up to 69%, but usually 
mild to moderate. Grade 3 and 4 nausea and vomiting were noted in 14%. 
Diarrhea was seen in 19%, stomatitis in 11%, and constipation in 23%. 
Pulmonary: Dyspnea was seen in 23%, severe in 3%. Rarely parenchymal 
toxicity including pneumonitis has been reported. Treatment should be 
discontinued immediately, if suspicious symptoms occur. 
Hepatic:  Transient elevation of hepatic enzymes was seen in 70%, 
however, this was not dose dependent and no increase was noted during 
prolonged therapy. Serious hepatotoxicity, including liver failure and 
death, has been reported very rarely.  
Fever: This is seen in up to 41%, but usually of a mild degree. Fever may 
be accompanied by flu-like symptoms in 19%.  
Renal: Reversible proteinuria, hematuria are frequent; increased BUN and 
creatinine in 16% and 8% of patients, respectively. However, renal 
insufficiency or hemolytic uremic syndrome is very rare. If suspicious 
symptoms are noted therapy should be discontinued immediately. 
Dermatologic/Skin:  Alopecia is seen in 15%; a reversible macular or 
macular-papular rash is seen in 30%; pruritus occurs in 13%. Peripheral 
edema is seen in up to 20% of the patients treated. Infusion site reactions 
occurred in 4% of patients. 
Neurologic: There was a 10% incidence of mild paresthesias; somnolence 
occurred in 11% of patients.   
Pain at the site of injection: Seen in 48% of patients; Grade 3 in 9%.   
Other: Cardiovascular or allergic reactions are seen very rarely.  
 
*See FDA-approved gemcitabine package insert for a comprehensive list 
of adverse events associated with gemcitabine. 
 

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4.3 
Radiation Therapy 
  
  
4.31 
Pelvic, Inguinal and Vulvar Radiation: IMRT (04/21/2014) 
 
 
IMRT is required for this study.  All patients will be treated using IMRT.  
Before ANY patient is enrolled on this study the treating radiation 
oncologist must complete an online a Knowledge Assessment 
Questionnaire for this study found on the IROC Houston (formerly the 
Radiologic Physics Center) website (http://irochouston.mdanderson.org 
under credentialing GOG). 
 
 
All institutions MUST be credentialed by IROC Houston at M.D. 
Anderson Cancer before entering any patient on this study (See Section 
5.1). Institutions that have been previously credentialed for IMRT by 
GOG or any other NCI-funded Study Group via the head and neck 
phantom or pelvic phantom can determine what additional requirements 
must be completed by filling out the “Credentialing Status Inquiry” form 
on the IROC Houston website (http://irochouston.mdanderson.org). IROC 
Houston will issue credentials for this protocol to the institution and notify 
the GOG Statistical and Data Center (SDC). 
 
 
The treatment plan for all patients treated on this protocol must be 
submitted via TRIAD.) After the data has been submitted via TRIAD, 
complete a DDSI information form found at 
http://www.rtog.org/CoreLab/TRIAD.aspx.The case will be processed in 
preparation for rapid review. A rapid review will be performed for each 
patient PRIOR TO DELIVERING ANY PROTOCOL TREATMENT. 
The rapid review will be initiated and 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. In addition, to help 
delineate the extent of vulvar involvement and to help ensure adequate 
volume definition for the boost, an electronic photograph will be 
submitted with the treatment plan.  (08/26/2013) 
 
All patients who have undergone surgical resection of the groin lymph 
nodes will initiate radiation within 6 weeks of surgery. 
 
 
 
4.32 
Technical Factors 
 
4.321 Megavoltage equipment capable of delivering static intensity 
modulation with a multi-leaf collimator or a dynamic intensity 
modulation (using a multi-leaf collimator or tomotherapy) is 
required. Forward-planned IMRT (field in field) treatment 
planning methods are required.   
 

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4.322 Recognizing that higher photon energies with higher monitor units 
increase the neutron contamination, a 6-10 MV photon beam 
energy is preferable.  Beam energies greater than 10 MV photons 
are still permissible.  
 
  
4.33 
Patient Immobilization 
 
Patient must be placed in an appropriate immobilization device to ensure 
stability of the treatment position. The preferred position is supine with 
frog leg position to avoid dose to the upper thigh skin, but straight leg 
position is acceptable. Bolus material must be used to cover the entire 
vulva to ensure adequate surface dose. This may be accomplished with 
either bolus material or with the patient’s thigh tissue acting as self bolus 
as per section 4.3631.  Because of the required use of low pelvic nodal 
treatment, it is recommended that simulation and treatment be done with a 
full bladder.  
 
  
4.34 
Simulation (04/21/2014) 
 
 
CT simulation is required to define the gross tumor volume (GTV), 
clinical tumor volume (CTV), and planning tumor volume (PTV). The CT 
scan must be acquired in the same position and immobilization device as 
for treatment. The use of IV contrast and bowel prep-contrast is encourage 
for better delineation of the contrast-enhanced pelvic vessels used as a 
surrogate for regional nodal delineation as well as small bowel contouring, 
respectively. Skin markers must be placed on the vulva to circumscribe the 
extent of visible gross disease to ensure that all gross disease is delineated 
on the planning CT scan.  
 
For submission to TRIAD the structure names MUST match exactly with 
this list or resubmission may be required. 
 
Structure Name 
Description 
GTVp 
 Vulvar GTV is defined as the gross tumor as 
seeon radiaographic imaging or as visible on 
clinical exam. 
Required 
GTVn 
Inguinal  GTV is defined as unresected or residual 
gross disease in the inguinal-femoral region as 
defined on any radiographic imaging. 
Required 
CTVp 
Vulvar CTV is defined as the vulvar GTV with a 2 
cm margin that includes the surrounding skin and 
subcutaneous tissue. 
Required 

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CTVn 
Inguinal CTV is defined dependent on the 
presence of inguinal GTV.  Both inguinal regions 
will be treated in all patients regardless of 
laterality of the tumor. 
Required 
PTVp_6400* 
Vulvar PTV, PTV expanded to encompass CTVp 
by a 7 mm to 10 mm margin. 
Required when applicable 
PTVn_6400* 
Inguinal PTV, PTV expanded to encompass CTVn 
by a 7 mm to 10 mm margin. 
Required when applicable 
PTVp_6000* 
Vulvar PTV, PTV expanded to encompass CTVp 
by a 7 mm to 10 mm margin. 
Required when applicable 
PTVn_6000* 
Inguinal PTV, PTV expanded to encompass CTVn 
by a 7 mm to 10 mm margin. 
Required when applicable 
PTVp_4500* 
Vulvar PTV, PTV expanded to encompass CTVp 
by a 7 mm to 10 mm margin. 
Required when applicable 
PTVn_4500* 
Inguinal PTV, PTV expanded to encompass CTVn 
by a 7 mm to 10 mm margin. 
Required when applicable 
Bladder 
Bladder 
Required 
Rectum 
Rectum 
Required 
BowelSpace 
Small Bowel 
Required 
Femurs 
Femurs 
Required 
NonPTV 
External minus the PTVs 
Required 
External 
External Skin 
Required 
Required When Applicable.  
 
  
4.35     Dose Specifications 
 
  
 
4.351 Dose to Designated PTVs 
 
  
4.3511    The vulvar PTV and the groin PTV when inguinal nodes 
are unresectable will receive 64 Gy in 32 fractions. 
Treatment will be delivered once daily, 5 days per week 
for 7 weeks. Breaks from treatment should be minimized 
and reasons for breaks must be documented. (08/15/2016) 

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4.3512  The groin PTV when high-risk positive nodal features are  
 
 
 
 
present (as defined in Section 5.4) will receive 60 Gy in 
30 fractions. Treatment will be delivered once daily, 5 
days per week for 6 weeks. 
 
4.3513 The groin PTV and the pelvic PTV after resection of  
pathologically negative inguinal lymph nodes, or resected 
positive nodes that have low-risk features will receive 45 
Gy in 25 fractions. Radiation of the pelvis and groins 
after dissection with negative lymph nodes on final 
pathology is at the discretion of the investigator. 
 
4.352 IMRT Dose Designation to Designated PTV 
 
The dose is prescribed to cover 97% of the vulvar PTV and the 
inguinal PTV and pelvic PTV.  A volume of at least 0.03 cc within 
any PTV should not exceed >110% of the prescribed dose to each 
PTV.   No volume within each of the PTVs that is 0.03 cc or 
greater shall receive less than 93% of its prescribed dose.  
 
4.36 
Contouring the Target Volumes 
 
 
4.361 Please refer to the RTOG Gynecologic Atlas for volume 
specifications.  
 
 
4.362 Gross Tumor Volume (GTV) 
 
 
 
 
4.3621 Vulvar GTV is defined as the gross tumor as seen on  
  
 
radiographic imaging or as visible on clinical 
examination, radiographic imaging and delineated with 
surface markers on the planning CT scan. Skin markers 
must be placed on the vulva to demarcate the extent of 
gross visible disease on the vulva to ensure that all gross 
disease is delineated on the planning CT. An electronic 
photo will be submitted as well to define the extent of 
vulvar tumor involvement. (08/26/2013) 
 
4.3622 Inguinal GTV is defined as unresected or residual gross 
disease in the inguinal-femoral region as defined on any 
radiographic imaging. 
 
 
  
 
4.363 Clinical Tumor Volume (CTV) 
 

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4.3631 Vulvar CTV is defined as the vulvar GTV with a 2 cm 
margin that includes the surrounding skin and subcutaneous 
tissue.  
 
 CTV shall not extend outside the skin and shall exclude 
bony tissue unless there is documented gross bony 
involvement. To ensure adequate dose to the skin, bolus 
material or self-bolus with the patient’s tissue (thigh) will 
be utilized. 
 
4.36311 
Vaginal involvement: When the vulvar GTV  
  
involves/extends into the vagina, then a 
minimum of 2 cm of normal vagina will be 
included in the vulvar CTV. It is acceptable 
to include the entire vagina in the CTV.   
 
 
4.36312 
Perianal skin/anorectum: When the GTV 
involves or extends to within 1 cm of the 
anal verge, then a minimum of 2 cm of 
normal anorectum will be included in the 
vulvar CTV.   
 
4.36313 
Periurethral/urethra: When the GTV 
involves the urethra or periurethral tissue 
then a minimum of 2 cm along the urethra 
will be included in the vulvar CTV. 
 
 
 
4.3632 
 Inguinal CTV is defined dependent on the presence of 
inguinal GTV.  Both inguinal regions will be treated in all 
patients regardless of laterality of the tumor. Only 
exception is in the case of bilateral lymph node dissection 
that yields negative lymph nodes, in which case radiation of 
the inguinal areas and low pelvis are at the discretion of the 
treating radiation oncologist. 
 
4.36321 
Inguinal CTV in the absence of an inguinal 
GTV will extend 2.5 cm lateral and 3 cm 
medial to the nearest inguinal vessel as well 
as 2 cm anterior and 1 cm posterior to the 
vessels. The cephalad border of the inguinal 
nodes is at the top of superior pubic rami. 
The caudal extent of the inguinal nodal  
  
CTV is at the level of the bottom of the 
lesser trochanter.  Any postoperative 
changes from the inguinal-femoral 
dissection should be included in the CTV.  
The inguinal CTV should not include any of 

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the musculature of the proximal thigh. This 
volume will not extend outside the skin but 
will exclude the skin and surface by at least 
3 mm.18 
 
 4.36322 
Inguinal CTV in the presence of inguinal 
GTV will include the same volume as 
defined in Section 4.36321 but also extend 
(if needed) to include the inguinal GTV with 
a minimum 7 mm margin beyond the GTV. 
If there is evidence of skin involvement the 
CTV will extend to include the skin and 
bolus material will be used to ensure 
adequate dose to the skin. 
 
4.36323 
Pelvic nodal CTV is defined as the nodal 
regions at risk for the presence of 
microscopic disease. Each volume will 
include the vasculature of each nodal region 
with a minimum 7 mm expansion but 
excludes muscle and bone. Pelvic nodal 
CTV for all patients shall include bilateral 
external iliac, obturator and internal iliac 
nodal regions. Treating radiation oncologists 
should consider treatment of pelvic nodal 
regions if extensive vagina, anorectum  
  
  
 or urethral involvement is seen even in the 
absence of inguinal nodes on initial 
dissection. 
 
4.36324 
Planning tumor volume should provide a 7-
10 mm margin in all directions around the 
vulvar, inguinal and pelvic CTVs. Involved 
vulvar skin should have appropriate bolus 
material (or self-bolus) to ensure adequate 
dose to the skin. The PTV in this situation 
shall NOT be pulled back from the skin in 
the planning process. 
 
 
 
4.364 Clinical Normal Structures 
 
 
 
  
4.3641 Bladder will be contoured in each slice in which it appears. 
 
4.3642 Ano-rectum will be contoured in each slice in which it 
appears.  
 

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The radiation oncologist should consider the maximum 
caudal extent of the rectum to extend to the perineum but 
for calculating constraints the anorectum within the PTV 
will be subtracted from the total anorectal volume. The 
superior extent of the rectum where the sigmoid begins 
should be marked by the increased curvature/tortuosity of 
the bowel.  
 
4.3643 Small bowel will be contoured on each slice in which it 
appears, extending 2 cm above the most cephalad PTV. 
The small bowel volume should consider all the bowel 
loops and any place within the peritoneal cavity small 
bowel could lie such as the mesentery and adipose tissue. 
 
4.3644 Femoral head/neck will be contoured to include the entire  
 
femoral head and extend down to the top of the lesser 
trochanter. 
 
4.37 
Constraints 
 
Participants are strongly encouraged to respect the following limits but the  
appropriate treatment of the tumor volumes is the first and primary 
objective: 
 
  
 
4.371 Small bowel: < 30% to receive ≥ 40%; Dmax ≤ 51 Gy 
 
4.372 Anorectum (this constraint should exclude any PTV that overlaps 
this volume): < 80% to receive ≥ 40 Gy; Dmax < 65 Gy 
 
  
 
4.373 Bladder:  < 50% to receive ≥ 45 Gy; Dmax ≤ 65 Gy 
 
4.374 Femoral heads/neck: < 50% to receive ≥ 45 Gy; Dmax ≤ 55 Gy 
 
4.375 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 1 cc 
(whichever is smaller) of the tissue outside the PTV will receive > 
110% of the prescribed vulvar PTV.  However, with respect to this 
last constraint it is recognized that there may be patients in which, 
due to obesity or other factors, this constraint may not be 
obtainable if other constraints, e.g. rectum, are met. In these cases 
it is recommended that the OAR constraints be favored to the 
extent possible that is consistent with good radiotherapeutic 
practice. 
 
4.38 
Documentation Requirements 

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4.381  All plans and the electronic photo must be submitted electronically  
via TRIAD for review, in addition to what is required from IROC 
Houston in Section 5.1. (08/26/2013) (04/21/2014) 
 
 4.382 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.  
4.383 Submission of digital data via TRIAD (04/21/2014) 
 
Digital RT Data Submission to Using TRIAD 
TRIAD is the American College of Radiology’s (ACR) 
image exchange application and it is used by IROC- 
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. 
 
4.39  Treatment Schedule:  All fields are treated with each fraction, treating 
once per day, five days per week.  It is anticipated that radiation therapy 

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will start as soon as clinically feasible at the discretion of the treating 
physician but within 6 weeks of enrollment. (08/26/2013) (08/15/2016) 
 
4.310 Therapy Interruptions: If interruption of two weeks or less occurs, 
radiation should be completed to the prescribed total dose.  Therapy 
interruptions of more than two weeks will be considered a major or minor 
deviation from the protocol, depending on clinical circumstances, and 
resumption of therapy will be at the discretion of the radiation oncologist.  
Follow-up must continue regardless of radiation treatment received. 
 
4.311 Radiation Therapy Quality Control and Documentation: IROC Houston is 
funded by the NCI to support clinical trials employing radiation therapy 
and will supervise the dosimetry quality control for this clinical trial. 
 
4.312 In the first 5 days of treatment, each patient will have in-vivo dosimetry 
performed to evaluate the dose of radiation to the vulva. The dosimetry 
applicator will be provided by IROC Houston and returned to them for 
evaluation. The dosimeter will be placed on the vulvar surface, under 
bolus if used or in skin folds if positioning of patient is with legs together.  
 
4.4 
Pathology Requirements 
 
4.41 
Eligibility Criteria 
 
Patients must have locally-advanced, previously untreated squamous cell 
carcinoma of the vulva. This protocol is for T2 or T3 primary tumors (N0-
3, M0) that are not amenable to surgical resection by standard radical 
vulvectomy. 
 
4.42 
Requirements 
 
(Correlation of pathology requirements with the flow chart at the 
beginning of this protocol is recommended). 
  
One H&E stained slide to confirm the initial diagnosis of invasive 
squamous carcinoma of the vulva is required. Other tumor types are not 
eligible for this protocol. 
 
If patients have (pretreatment) resectable lymph nodes: 1) If lymph nodes 
contain metastatic carcinoma, H&E stained slides of the resected lymph 
nodes are required in order to document metastatic carcinoma; 2) If lymph 
nodes are negative for metastatic tumor, a copy of the pathology report is 
required (slides of negative lymph nodes are not required). 
 
In patients with (pretreatment) unresectable lymph nodes, H&E slides 
documenting residual squamous cancer (post-radiation resection) are 

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required. If there is no residual tumor (post-radiation), copies of all fine 
needle aspirate and surgical pathology resection reports documenting 
negative lymph nodes are required (slides from negative lymph nodes are 
not required). 
 
After cisplatin + Gemcitabine + IMRT, the following H&E slides are 
required: 1) A surgical pathology report documenting absence of tumor if 
there is no residual neoplasm (slides are not required if there is no residual 
tumor); 2) At least one H&E slide documenting residual carcinoma from 
the surgical resection in patients whose residual disease is resected; 3) if 
residual disease is documented by a method other than histology, the 
method of determining that residual disease is present should be stated. 
Please see sections 7.2 and 10.2 for additional instructions. 
 
 
 
 

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5.0 
TREATMENT PLAN AND ENTRY/RANDOMIZATION PROCEDURE (04/21/2014)    
 
5.1 
IROC HOUSTON (FORMERLY THE RADIOLOGICAL PHYSICS CENTER 
[RPC]) CREDENTIALING REQUIREMENTS (04/21/2014) 
 
5.11 
Credentialing for this protocol will be handled by IROC Houston. All 
information regarding credentialing can be found on the IROC Houston 
website (http://irochouston.mdanderson.org) by selecting “Credentialing,” 
then “GOG.” 
 
5.12 
Before ANY patient is enrolled on this study, each the treating radiation 
oncologist must complete online a Knowledge Assessment Questionnaire 
for this study found on the IROC Houston website. 
 
5.13 
IMRT Credentialing requirements: 
 
Institutions must be credentialed for IMRT by IROC Houston for this 
protocol prior to enrolling patients into this study.  Each institution must 
successfully irradiate a standardized phantom available from IROC 
Houston. Instructions for requesting and irradiating the phantom are 
available at the IROC Houston web site. The treatment plan for irradiation 
of the phantom must be submitted electronically to TRIAD. Institutions 
that have been previously credentialed for IMRT or any other NCI-funded 
Study Group via the head and neck phantom or the pelvic phantom can 
determine what additional requirements must be completed by filling out 
the “Credentialing Status Inquiry” form on the IROC Houston’s website. 
IROC Houston will issue credentials for this protocol to the institution and 
notify the GOG Statistical and Data Center (SDC). 
 
 
Each Institution must complete the IMRT Facility Questionnaire available 
on the IROC Houston web site by selecting “Credentialing,” then “GOG,” 
then the specific protocol credentialing requirements.” Each institution 
must submit the completed IMRT Facility Questionnaire online.  
 
Institution and/or peer-reviewed documentation of target position 
reproducibility [planning treatment volume (PTV) and clinical target 
volume (CTV)] must be consistent with Section 4.34 and 4.36. 
 
5.14 
Digital RT Data Submission Using TRIAD (04/21/2014) 
 
Each institution must set up a TRIAD account prior to any patient 
enrollment 
 
TRIAD is the American College of Radiology’s (ACR) image 
exchange application and it is used by IROC Houston (RPC). 
TRIAD provides sites participating in clinical trials a secure 

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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. 
. 
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>.  

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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>. 
 
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:   

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Site registration forms may be downloaded from the GOG-0279 
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 # 
0279 
Click on the Site Registration Documents link 
 
5.223 Requirements for GOG-0279 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.  
 
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 

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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).  
  
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.  

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Note:  The OPEN system will provide the site with a printable 
confirmation of registration and treatment information.   Please print this 
confirmation for your records.  
  
Further instructional information is provided on the CTSU members' web 
site OPEN tab or within the OPEN URL. For any additional questions 
contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com.  
 
5.4 
Treatment Plan (08/15/2016) 
 
All patients who are eligible for this protocol (See Section 3.0) with T2 or T3 
primary tumors (N0-3, M0) not amenable to surgical resection by standard radical 
vulvectomy will be treated according to this regimen.  There is no randomization. 
Although it is preferable to have patients registered for the trial prior to the lymph 
node surgical evaluation, patients may be registered/enrolled postoperatively. If 
patients do not register/enroll until postoperative from the groin node assessment, 
the treating physicians should determine if patients meet eligibility requirements 
(requirement 3.13 can be determined as part of standard practice in preoperative 
lab work) and confirm that they and the patient agree the treatment protocol is 
appropriate and acceptable therapy.   
 
Surgery:  Patients with clinically negative or resectable groin nodes will undergo 
pretreatment inguinal – femoral lymph node dissection or sentinel lymph node 
biopsy at the discretion of the treating surgeon and prior to registration.  Six to 8 
weeks following completion of chemoradiation patients will undergo local core 
biopsy of the tumor bed to confirm complete pathologic response or surgical 
excision of gross residual disease in the vulva and/or inguinal-femoral lymph 
nodes.  If the inguinal – femoral lymph nodes were initially deemed unresectable, 
an FNA of persistent clinical or radiographic suspicious lymph nodes 6-8 weeks 
after completion of radiation is acceptable.  If the FNA is positive, a targeted 
excision of the groin should be done.  A radical vulvectomy is not necessary.  If 
there has been complete clinical response, an excisional biopsy of the primary 
tumor site to confirm pathologic response should be performed.   
 
Radiation:  Radiation therapy will be delivered by IMRT to the vulva, inguinal-
femoral lymph nodes, and lower pelvic lymph nodes. As time to recover from a 
sentinel lymph node biopsy is different from a inguinal femoral dissection, 
commencement of radiation operatively will be at the discretion of the treating 
physician however, patients must be registered/enrolled in the trial within 2 weeks 
of surgery and IMRT must start no later than 6 weeks after surgery or 
determination of unresectable nodes.   
 
- 
The vulvar CTV will receive 64 Gy regardless of the groin node dose. 
 

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- 
Patients with negative groin nodes as determined by pretreatment 
inguinal-femoral lymph node dissection will receive radiation therapy to 
the vulva and may receive radiation therapy to the inguinal-femoral and 
lower pelvic lymph nodes at the discretion of the treating physician. If 
treatment to the groins/low pelvis is elected, the total dose will be 45 Gy.   
 
- 
For those with positive lymph nodes by inguinal-femoral lymph node 
dissection, radiation will be delivered to a dose of 50 Gy and with a boost 
to 60 Gy on any/both sides that have high risk nodal features. These 
features include those inguinal nodes affected by  ≥ 3(+) LN, extracapsular 
extension, or close/positive margin.   For those patients with unresectable 
lymph nodes, patients will receive radiation to a dose of 64 Gy.   
 
Post-Radiation evaluation: An FNA of any clinical or radiographic residual 
disease in the groin or vulva will be performed 6-8 weeks after completing 
radiation.  Those that have a positive FNA will undergo a targeted excision.   
 
Chemotherapy:  Patients will receive concurrent Cisplatin 40 mg/m2 and 
Gemcitabine 50 mg/m2 administered weekly throughout radiation therapy.  
Gemcitabine will be infused prior to cisplatin and given over approximately 30 
minutes while the cisplatin will be delivered over approximately 60 minutes.  The 
maximum dose of cisplatin is stated in Section 6.0, and applies to those with a 
BSA >1.75m2.  
 
Chemotherapy should start on the same day as the start of radiation. There is no 
required timeframe for chemotherapy (i.e. before or after radiation) for on the day 
of radiation. 
 
Please follow institutional standards for antiemetics and hydration pre- and post-
cisplatin.  Please follow institutional standards for the preparation of cisplatin and 
gemcitabine.  (08/26/2013) 
 
5.41 
See Appendix II, GOG General Chemotherapy Guidelines 
 
 

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6.0 
TREATMENT MODIFICATIONS (08/15/2016) 
 
   
Dose Delay (08/15/2016) 
  
ANC <500 
Platelets <50,000* 
ANC 500-1,000 
Platelets 50,000-100,000 
ANC >1,000 
Platelets >100,000 
Cisplatin 
Holda 
Treat normally  
Treat normally   
Gemcitabine 
Hold  
 Treat normally  
Treat normally   
XRT 
Hold  
Treat normally   
 Treat normally  
a Dose reduction 
*For the second episode ANC <500 and platelets <50,000 see sections 6.141 and 6.211. 
 
 
Dose Modifications (08/15/2016) 
Study Drug  
2 Level reduction 
1 Level reduction 
Initial dose level 
 
Cisplatin 
20 mg/m2 
(max=35mg*) 
(11/13/2012) 
30 mg/m2 
(max=52.5mg*) 
(11/13/2012) 
40 mg/m2 
(max=70mg*) 
Gemcitabine 
25 mg/m2 
37.5 mg/m2 
50 mg/m2 
 
* For cisplatin, the max doses apply to those with BSA > 1.75 m2 
(08/26/2013) 
 
NOTE:  There will be no dose re-escalations after dose reduction.  Only 2 dose 
reductions are allowed. (08/26/2013) 
 
NOTE:  If radiation is held for any reason, then chemotherapy should also be 
held.  If one of the chemotherapy drugs is held or discontinued for 
toxicity, but the other is tolerated, that drug may be continued. 
(08/26/2013) 
 
Please note all CTCAE grading below refers to version 4.0. 
 
 
6.1  
Cisplatin Modifications (see Section 6.2 for Gemcitabine Modifications) 
 
6.11  Gastrointestinal Adverse Effects 
 
6.111  Nausea: Prior to infusion of cisplatin, the use ondansetron, 
granisetron, dolasetron and/or Aprepitant is strongly 
recommended. Lorazepam may also be given if desired. 
 
6.1111 For protracted grade 3 toxicity with nausea and vomiting 

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lasting two or more days or requiring hospitalization or 
TPN > 24 hours, cisplatin will be reduced by one dose 
level. 
 
6.1112 For protracted Grade 4 toxicity despite maximal medical 
therapy, a two level dose reduction should be made.  If a 
participant was previously reduced by one dose level, and 
then experiences protracted grade 4 nausea, the lowest dose 
is 20mg/m2, per the table above. (08/26/2013) 
 
6.112  Diarrhea:  Usually can be controlled with low-fiber, low-fat, bland 
diets and anti-diarrheal medications.  Should GI toxicity become 
severe, hospitalization may be required at which time the treatment 
may be interrupted temporarily until the patient’s condition 
improves.  If the patient does not recover to baseline within 2 
weeks of last treatment, the patient will be removed from study 
treatment. 
 
6.12 
Renal/Genitourinary Adverse Effects 
 
 6.121  If creatinine rises to greater than 1.5 mg/dL, obtain creatinine  
clearance (CrCl). Creatinine clearance should be obtained via the 
Crockcroft Gault calculation.  Cisplatin dosing will be managed 
based on creatinine clearance as follows: (08/26/2013) 
 
6.1211 If CrCl is 50 ml/min or greater, continue cisplatin at current 
dose level.  (08/26/2013) 
 
6.1212 If the CrCl is less than50 ml/min, hold cisplatin. The CrCl 
should be checked weekly.  If the CrCl returns to or 
surpasses 50 ml/min, resume cisplatin chemotherapy with a 
one dose level reduction.  (11/13/2012) (08/26/2013) 
 
6.1213 If the CrCl remains under 50 ml/min for more than 4 
weeks, the patient will be removed from study treatment 
and we recommend that cisplatin should be discontinued. 
NOTE: follow-up of patient is still required. (08/26/2013) 
 
6.1214  Selective renal tubular defects are sometimes observed:  
hypocalcemia with hypomagnesemia and hypokalemia are 
common and potentially severe. The aggressive 
replacement of magnesium, calcium and potassium is 
required. Severe tubular effects, although rare, may require 
chronic replacement therapy. Diagnostic tests for 
alternative mechanisms of hypocalcemia (e.g. GI or 
metabolic) should be considered. 

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6.13 
Neurologic Adverse Effects 
 
6.131  CTCAE Grade 1 - No change 
 
6.132  CTCAE Grade 2 - Reduce cisplatin by one dose level 
 
6.133   CTCAE Grade 3 or 4 - Hold cisplatin until recovered to ≤ grade 2 
and then resume at one dose level reduction 
 
6.14  Blood/Bone Marrow (Hematologic) Adverse Effects  
 
NOTE:  If chemotherapy is delayed but blood counts are sufficient to 
continue or re-start radiation, then radiation should be resumed even 
without chemotherapy (see Section 6.3) 
 
6.141 Neutropenia 
 
Patients will be followed by the absolute neutrophil count (ANC), 
not the white blood cell count (WBC). Cisplatin should be 
administered as long as ANC ≥ 500/mcl and platelet count is ≥ 
50,000/mcL. 
 
For ANC < 500/mcl, hold the cisplatin.  Repeat the complete blood 
count three times a week until the patient recovers to or exceeds 
500/mcL. The maximum delay allowed is four weeks. Patients 
who do not recover within this time will be removed from study 
treatment. (08/26/2013) 
 
Gemcitabine alone will be dose reduced for hematologic toxicity 
(See Section 6.211).  Should patients require reduction to dose-
level -2 due to recurrent febrile neutropenia (and/or documented 
grade 4 neutropenia lasting ≥ 7 days), then cisplatin will be dose 
reduced by one dose level.  Patients who experience repeat febrile 
neutropenia and/or documented grade 4 neutropenia lasting ≥ 7 
days despite Gemcitabine administered at Dose Level -2 (plus 
cisplatin administered at Dose Level -1) will be removed from 
study treatment. 
 
6.142 Platelets  
 
There are no planned dose reductions for cisplatin due to 
thrombocytopenia.  Platelets ≥ 50,000/mcL is required for 
treatment. If platelet counts do not meet this threshold they should 
be repeated three times a week until recovery. The maximum delay 
allowed is four weeks. Patients who do not recover within this time 

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will be removed from study treatment.   
 
6.15 
Non-Hematologic Adverse Effects: (08/26/2013) 
 
6.151 All other non-hematologic toxicities with an impact on organ 
function ≥ grade 2 require reduction of one dose level in cisplatin 
and gemcitabine and delay in subsequent therapy for a maximum 
of 2 weeks until recovery to grade 1. 
 
6.2 
Gemcitabine Modifications 
 
6.21 
Hematologic Adverse Effects.  
NOTE: If chemotherapy is delayed but blood counts are sufficient to 
continue or re-start radiation, then radiation should be resumed even 
without chemotherapy (see Section 6.3).  
 
6.211 Neutropenia (08/26/2013) 
 
  
Gemcitabine treatment requires ANC ≥500/mcl.  For patients who 
do not meet this criteria, blood counts should be repeated three 
times a week until recovery.  
 
 
The first time a patient has an ANC <500 lasting greater than 1 
week, a dose reduction will occur.  If a second ANC<500 occurs, 
they will have 2 weeks to recover before another dose reduction is 
required. 
 
If treatment is delayed ≥ 2 weeks, subsequent doses should be 
reduced one dose level (see Section 6.15).  The maximum delay 
allowed is four weeks. Patients who do not recover within this time 
will be removed from study treatment. 
 
Febrile neutropenia. For first occurrence of febrile neutropenia 
and/or documented grade 4 neutropenia persisting ≥ 7 days, 
gemcitabine will be reduced by one dose level in subsequent 
cycles.   
 
For second occurrence of febrile neutropenia and /or recurrent 
documented grade 4 neutropenia persisting ≥ 7 days (after initial 
dose reduction), add prophylactic G-CSF.  Gemcitabine dose will 
not be further reduced.  It is recommend that G-CSF be dosed at 5 
mcg/kg/day and be administered subcutaneously starting the day 
after the last chemotherapy and continuing through hematopoietic 
recovery. It should not be given within 72 hours of a subsequent 
dose of chemotherapy.  (11/13/2012) 
 

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Patients with a third recurrence of febrile neutropenia and or 
documented grade 4 neutropenia lasting ≥ 7 days (despite  initial 
dose reduction and addition of G-CSF) will undergo further  dose 
reduction of gemcitabine to dose level -2. 
 
Patients who experience recurrent febrile neutropenia and or 
documented grade 4 neutropenia lasting ≥ 7 days despite the above 
interventions will undergo a dose reduction of Cisplatin as 
described above (See Section 6.141). 
 
If any additional episodes of febrile neutropenia and or 
documented grade 4 neutropenia lasting ≥ 7 days occur, the patient 
should be removed from study treatment. 
 
6.212   Thrombocytopenia. Gemcitabine treatment requires platelet count 
≥ 50,000/mcL. For patients who do not meet this criteria, blood 
counts should be repeated three times a week until recovery.   
 
Patients with grade 4 thrombocytopenia will have a 1 level dose 
reduction of gemcitabine. No dose reductions are required for 
grade 3 or less thrombocytopenia. 
  
 
 
 
If treatment is delayed ≥ 2 weeks, subsequent doses should be 
reduced one dose level. 
 
If therapy has been delayed for 4 weeks or more from scheduled 
administration, the Study Chair will be notified and patient 
removed from study treatment, but follow up will continue.  If 
chemotherapy is delayed but blood counts are sufficient to 
continue or re-start radiation, then radiation should be resumed 
even without chemotherapy.  
 
6.22 
Non-Hematologic Adverse Effects: (11/13/2012) (08/26/2013) 
 
 
For Grade 3 or greater elevations of AST, ALT, alkaline phosphatase or  
Bilirubin, both cisplatin and gemcitabine should be delayed for a 
maximum of 2 weeks until recovery to grade 1.  The patient will then 
restart the cisplatin at the current dose, and the gemcitabine at a one dose 
level reduction for all subsequent cycles. 
 
6.221 All other non-hematologic toxicities with an impact on organ 
function ≥ grade 2 require a delay in subsequent therapy for a 
maximum of 2 weeks until recovery to grade 1 and then a 
reduction of one dose level in cisplatin and gemcitabine for 
subsequent cycles. 
 
 
 
 

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6.3  
Radiation Modifications: 
 
Every attempt should be made to avoid radiation treatment interruptions.  There 
are no scheduled radiation breaks.  However, cutaneous reactions (as well as GI 
and GU symptomatology) may be expected with this treatment regimen.  All 
symptoms should be managed aggressively with medications and skin care 
measures.  Treatment breaks may be needed for confluent moist desquamation 
(cutaneous ulceration) or severe GI or GU toxicity, but interruptions should be 
kept to an absolute minimum.  Also radiation should be withheld for a 
granulocyte count < 1000/uL or a platelet count < 40,000/uL.  Patients on study 
should be given PRBC (packed red blood cell) transfusions as needed to keep 
weekly hemoglobin levels > 10 g/L.  The prescribed course of therapy without 
breaks lasts 6.5 weeks. All composite radiation therapy breaks greater than 14 
days (2 weeks) should be discussed with the Radiation Therapy Study Chair. 
 
6.31 
Cutaneous Adverse Effects: 
 
Grade 0-2:  No dose modifications.  Skin hygiene and precautions should 
be emphasized.  The use of cornstarch and non-perfumed aloe vera lotions 
or aquaphor may be helpful  
 
Grade 3:  Hold radiotherapy and chemotherapy.  Treat patients with 
Silvadene cream, sitz/therapeutic whirlpool baths, Domboro soaks, 
Nastatin/Tetracycline/Benadryl/Hydrocortisone elixir, analgesic and 
antibiotics as appropriate and necessary.  Re-evaluate twice weekly for 
recovery. 
 
Grade 4:  Hold radiotherapy and chemotherapy.  Treat same as grade 3 
above.  Notify Radiation Therapy Study Chair. 

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7.0 
STUDY PARAMETERS   
 
7.1 
Observations and Tests (08/15/2016) 
The following observations and tests are to be performed and recorded on the 
appropriate form(s): 
PARAMETER 
 
 
Pre-
treatment 
 
 
Weekly 
During 
Treatment 
 
At the 
completion 
of radiation 
therapy 
Post 
Operative (at 
the post-
operative visit 
with the 
treating 
physician) 
(08/26/2013) 
Post 
Treatment 
Post 
Treatment 
Every 3 
months for 2 
years and 
every 6 
months for 3 
years  
(+/-10 day 
window)  
History & Physical 
to include pelvic 
exam (08/26/2013) 
4 
5 
 
 
 
X 
Tumor  
Assessment by 
Physical Exam 
4 
 
 
 
 
X 
Toxicity 
Assessment 
2 
5 
6 
9 (08/26/2013) 
 
X 
Performance Status 
(08/26/2013) 
 
X 
(08/26/2013) 
 
X 
(08/26/2013) 
 
6 (08/26/2013) 
 
 
 
CBC/Diff/ 
platelets1 
2 
5 
 
 
 
 
Clinical Chemistry 
2, 10 
5, 10 
(08/26/2013) 
 
 
 
 
Pregnancy test 
3 
 
 
 
 
 
Urinalysis 
2 
 
 
 
 
 
Radiographic 
Tumor 
Measurement 11 
(08/26/2013) 
4 
 
7 
 
 
 
Chest Imaging (x-
ray or CT scan of 
the chest) 
4 
 
 
 
 
 
Vulva Biopsy or 
FNA of the Groin 
 
 
 
 
8 
 
1. 
CBC is repeated three times per week for serious neutropenia (ANC<500) or thrombocytopenia (<50,000). See Sections 
6.141, 6.142, 6.211, 6.212. 
2. 
Must be obtained within 14 days of the initiation of protocol therapy. 

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3. 
For women with childbearing potential; must be obtained within 7 days of initiation of protocol therapy. 
4. 
Must be obtained within 28 days of the initiation of protocol therapy. 
5. 
Must be obtained within 4 days of re-treatment. 
6. 
Complete 1 week after the completion of radiation therapy. 
7. 
Complete 6-8 weeks after completion of chemo-radiation 
8. 
Should be performed approximately 6-8 weeks after completion of chemo-radiation treatment 
9. 
Post-operative toxicity assessment should be conducted after the initial lymph node dissection.  Post-operative toxicity 
assessments should also occur for patients who have a surgical resection of residual disease, or a target excision of 
positive lymph nodes post protocol treatment. (08/26/2013) 
10. Weekly chemistries should include Albumin, alkaline phosphatase, total bilirubin, calcium, chloride, glucose, 
phosphorus, magnesium, potassium, total protein, SGOT (AST), SGPT (ALT), sodium, BUN, and creatinine.  
(08/26/2013) 
11. Radiographic Tumor Measurement to include a CT Scan of the chest, abdomen, and pelvis.  (08/26/2013) 
 
7.2 
STAINED PATHOLOGY SLIDE REQUIREMENTS FOR CENTRAL REVIEW 
TO CONFIRM ELIGIBILITY (08/26/2013) 
 
Stained pathology slides are required for central review by the GOG Pathology 
Committee.  
 
7.21 
The following slides are required for all patients: 
 
1) 
 At least one representative H&E stained slide (or slides) 
demonstrating primary site, histologic cell type, and grade. 
 
2) 
 One H&E stained slide showing the most advanced stage of 
disease will be required if available.  If the most advanced stage of 
disease is not documented by histology, the method of stage 
documentation needs to be stated (e.g. CT, MRI, etc.).   
 
7.211 If patients have (pretreatment) resectable lymph nodes, the 
following additional H&E slides are required: 
 
 1) 
If lymph nodes contain metastatic carcinoma, H&E stained 
slides of the resected lymph nodes are required in order to 
document metastatic carcinoma; 
 2) 
If lymph nodes are negative for metastatic tumor, a copy of 
the pathology report is required (slides of negative lymph 
nodes are not required).  
 
7.212 In patients with (pretreatment) unresectable lymph nodes, the 
following additional slides are required: 
 
1) H&E slides documenting residual squamous cancer (post-
radiation resection) are required. If there is no residual tumor 
(post-radiation), copies of all fine needle aspirate and surgical 
pathology resection reports documenting negative lymph nodes 
are required (slides from negative lymph nodes are not 
required). 

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7.22 
The following slides are required for all patients after cisplatin + 
Gemcitabine + IMRT:  (04/21/2014) 
 
1) 
A surgical pathology report documenting absence of tumor if there 
is no residual neoplasm (slides are not required if there is no 
residual tumor); 
 
2) 
At least one H&E slide documenting residual carcinoma from the 
surgical resection in patients whose residual disease is resected. 
 
When submitting pathology material to the GOG SDC 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 4.4 and 10.2 for additional requirements and 
instructions. 
 
7.3 
Translational Research 
 
Not applicable for this protocol. 
 
 
7.4 
Quality of Life 
 
 
 
 
Not applicable for this protocol. 
 
 

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8.0 
EVALUATION CRITERIA   
 
8.1  
Objective Response 
 
 
8.11 
Complete clinical response--defined as no clinical/radiographic evidence 
of primary disease (vulva or groin) following primary chemo-radiation 
therapy. 
 
8.12 
Complete pathologic response (pCR) – defined among complete clinical 
responders with negative local core biopsy or FNA specimens. pCR is the 
sole primary endpoint. 
 
8.2 
Other Objective Response 
 
8.21 
Overall Survival – defined as the observed length of life from start of 
protocol therapy to death or, for living patients, the date of last contact. 
(08/15/2016) 
 
8.22 
Progression-free interval – defined as the date from start of protocol 
therapy to date of reappearance of disease or date of last contact. 
(08/15/2016) 
 
8.23 
Site of recurrence (or sites) to be noted regarding local (vulva, vagina) 
loco-regional (groin) or distant relapse. 
 
8.3 
Subjective Response 
 
Performance Status will be recorded on the patient’s record according to the 
standard GOG Performance Scale. 
 
8.4. 
Adverse Effects 
 
Adverse effect will be graded according to CTCAE v4 and reported on either 
form T (for acute effects) or form TLC (for delayed effects)  
 
 

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9.0 
DURATION OF STUDY    
 
 
9.1 
Patients will continue on study until disease progression or adverse effects 
prohibit further treatment. The patient can refuse the study treatment at any time. 
 
9.2 
All patients will be treated (with completion of all required case report forms) 
through the duration of the protocol treatment, until disease progression while on 
protocol treatment, unacceptable toxicity, or study withdrawal. Patients will then 
be followed (with physical exams and histories) every three months for the first 
two years and then every six months for the next three years. Patients will be 
monitored for delayed toxicity and survival for this 5-year period with Q forms 
submitted to the GOG Statistical and Data Center, unless consent is withdrawn. 
(08/26/2013) 

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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.  
 
The descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be 
utilized for AE reporting. All appropriate treatment areas should have 
access to a copy of the CTCAE version 4.0. A copy of the CTCAE version 
4.0 can be downloaded from the CTEP web site (http://ctep.cancer.gov). 
The CTCAE v4.0 Manual is also available on the GOG member web site 
(http://www.gog.org under MANUALS). 
 
10.12 Reporting Expedited Adverse Events 
 
Depending on the phase of the study, use of investigational 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-AERS.  
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  
 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
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Reporting Requirements for Adverse Events that occur within 30 Days¹ of the Last Dose of the 
Commercial Agent on Phase 2 and 3 Trials 
 
 
Grade 1 
 
Grade 2 
 
Grade 2 
 
Grade 3 
 
Grade 3 
Grades 
4 & 52 
Grades 
4 & 52 
Unexpected  
and Expected 
 
 
Unexpected 
 
 
Expected 
Unexpected 
Expected 
Unexpected Expected 
With  
Hospitali-
zation 
Without 
Hospitali- 
zation 
With  
Hospitali- 
zation 
Without 
Hospitali- 
zation 
Unrelated 
Unlikely 
Not 
Required 
Not 
Required 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
7 
Calendar 
Days 
Possible 
Probable 
Definite 
Not 
Required 
7 Calendar 
Days 
Not 
Required 
7 Calendar 
Days 
7 Calendar 
Days 
7 Calendar 
Days 
Not 
Required 
24-Hrs; 
3 Calendar 
Days 
7 
Calendar 
Days 
1 Adverse events with attribution of possible, probable, or definite that occur greater than 30 days after the last dose of 
treatment with a commercial agent require reporting as follows: 
CTEP-AERS 24-hour notification followed by complete report within 3 calendar days for: 
• Grade 4 and Grade 5 unexpected events  
      CTEP-AERS 7 calendar day report: 
• Grade 3 unexpected events with hospitalization or prolongation of hospitalization 
• Grade 5 expected events 
 
2 Although aCTEP-AERS 24-hour notification is not required for death clearly related to progressive disease, a full 
report is required as outlined in the table. 
 
 Please see exceptions below under the section entitled, “Additional Instructions or Exceptions to CTEP-AERS 
Expedited Reporting Requirements for Phase 2 and 3 Trials Utilizing a Commercial Agent.”          March 2005 
 
Note:  All deaths on study require both routine and expedited reporting regardless of 
causality.  Attribution to treatment or other cause must be provided. 
 
• 
Expedited AE reporting timelines defined: 
 “24 hours; 3 calendar days” – The investigator must initially report the AE via CTEP-
AERS within 24 hours of learning of the event followed by a complete CTEP-AERS 
report within 3 calendar days of the initial 24-hour report. 
“7 calendar days” – A complete CTEP-AERS report on the AE must be submitted within 
7 calendar days of the investigator learning of the event. 
 
• 
Any medical event equivalent to CTCAE grade 3, 4, or 5 that precipitates hospitalization 
(or prolongation of existing hospitalization) must be reported regardless of 
attribution and designation as expected or unexpected with the exception of any 
events identified as protocol-specific expedited adverse event reporting exclusions. 
 
 

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
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• 
Any event that results in persistent or significant disabilities/incapacities, congenital 
anomalies, or birth defects must be reported to GOG via CTEP-AERS if the event occurs 
following treatment with a commercial agent. 
 
• 
Use the NCI protocol number and the protocol-specific patient ID provided during trial 
registration on all reports. 
 
Additional Instructions or Exceptions to CTEP-AERS Expedited Reporting Requirements for 
Phase 2 and 3 Trials Utilizing a Commercial Agent: 
 
• All Grade 2 and 3 myelosuppression (including neutropenia, anemia, and 
thrombocytopenia) that does not require hospitalization is exempt from expedited 
reporting. 
 
10.14 Procedures for Expedited Adverse Event Reporting: 
 
10.141 CTEP-AERS Expedited Reports: Expedited reports are to be 
submitted using CTEP-AERS available at http://ctep.cancer.gov. 
The CTEP, NCI Guidelines: Adverse Event Reporting 
Requirements for expedited adverse event reporting requirements 
are also available at this site.  
 
AML/MDS events must be reported via CTEP-AERS (in addition 
to routine AE reporting mechanisms). In CTCAE v4.0, the event(s) 
may be reported as either: 1) Leukemia secondary to oncology 
chemotherapy, 2) Myelodysplatic syndrome, or 3) Treatment-
related secondary malignancy. 
 
In the rare event when Internet connectivity is disrupted, a 24-hour 
notification is to be made to GOG by telephone at: 215-854-0770. 
An electronic report MUST be submitted immediately upon re-
establishment of internet connection. Please note that all paper 
CTEP-AERS forms have been removed from the CTEP website 
and will NO LONGER be accepted. 
  
10.15 Automated CDUS reporting  
 
This study will be monitored by the Clinical Data Update System (CDUS) 
version 3.0. Cumulative CDUS data will be submitted quarterly to CTEP 
by electronic means.  Reports are due January 31, April 30, July 31 and 
October 31. 
. 
 
 

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10.2  GOG DATA MANAGEMENT FORMS 
 
The following forms must be completed for all patients registered and submitted 
according to the schedule below.  Protocol forms with the exception of the BDR 
form and Pathology Report must be submitted via the SDC Electronic Data Entry 
System (SEDES) which is available through the GOG Web Menu page 
(www.gogstats.org). 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 Statistical and Data 
Center (SDC).  Note: Pathology material (Form F, path report and slides) 
must be submitted together via postal mail. 
Form∆ 
Due within 
Copies
* 
Comments 
Weeks 
Event 
Knowledge Assessment 
(04/21/2014) 
0 
Prior to Registration 
1 
Available at 
http://irochouston.mdanderson.org 
under “Credentialing’ 
Form R (Registration Form) 
 
2 
Registration 
1 
Mandatory Submission via SEDES 
Form OSV (Primary Vulvar 
Cancer – On Study Form) 
2 
Registration 
1 
Mandatory Submission via SEDES 
Form DR (Pre-Treatment 
Summary Form) 
2 
Registration 
1 
Mandatory Submission via SEDES 
Form C (Surgical Reporting 
Form), Operative report and 
Discharge Summary for each of 
the following procedures: 
  - Lymph node dissection 
  - Surgical Resection 
  - Targeted Excision 
 
 
 
6 
 
 
 
 
Surgical Procedure 
 
 
 
1 
Available in SEDES for print only. 
Submit to SDC via postal mail or 
upload online via SEDES 
Form PV (Pathology Form-
Vulvar) 
6 
Surgical Procedure 
1 
Mandatory Submission via 
SEDES 
Form F, pathology report and 
stained slides for each of the 
following procedures: 
 - Biopsy of primary disease 
  - Lymph node dissection 
  - Surgical Resection 
  - FNA 
  - Targeted Excision 
 
6 
 
 
 
 
Surgical Procedure 
 
 
 
2 
 
 
 
 
Submit together to SDC via postal 
mail 
 or upload online via SEDES** 
 
 
 
Radiation Materials: 
- Daily treatment reports 
- CT/MRI showing relevant 
target volume 
- Simulation films or digitally 
reconstructed radiograph 
(DRR) 
- Portal films 
 
4 
Completion of 
Radiation Therapy 
 
Form G must be submitted via 
SEDES. Paper copies should also 
be submitted with radiation 
materials via postal mail. 
 
 
 

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- Dosimetry calculation 
- Isodose distribution curves 
- Form G (Radiation Treatment 
Form 
IMRT Plan electronically 
submitted via TRIAD 
(04/21/2014) 
- DDSI 
- Digital treatment planning 
data 
- Color isodose distribution 
- Dose Volume Histograms 
(DVH) 
-Electronic photograph to 
define extent of vulvar tumor 
involvement (08/26/2013) 
 
 
 
 
Submitted electronically via 
TRIAD  (04/21/2014) 
Form D2R (Cycle Dose Drug 
Form)1 
2 
Completion of each 
cycle of therapy 
1 
Mandatory Submission via SEDES 
Form T (Common Toxicity 
Reporting Form) 
2 
Beginning of each 
subsequent cycle, the 
completion of 
radiation therapy, 
post-op visit 
1 
 
Mandatory Submission via SEDES 
Form TLC (Follow-up Period 
Adverse Event Reporting 
Form) 
2 
Submit every three 
months for two years 
and every six months 
for three years during 
follow-up 
1 
Mandatory Submission via SEDES 
Form Q0 (Treatment 
Completion Form)2 
2 
Completion of study 
Rx and change in Rx 
1 
Mandatory Submission via SEDES 
Form Q (Follow-Up Form) 
 
2 
Disease progression; 
death; normal follow-
up 
1 
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. 
** 
At least one representative stained slide (or slides) documenting the primary and one representative stained 
slide documenting the most advanced stage are required for eligibility. See sections 4.4 and 7.2 for additional 
requirements and instructions.  
† 
Form SP must submitted via SEDES regardless of whether the specimen is submitted for research. 
1. 
Please note: One cycle is equal to one week of chemoradiation (or one week of radiation alone if chemo is 
held). 
2. 
In section 1 of Form Q0, please report the number of weeks of radiation therapy the patient received on study.  
In section 2 of Form Q0, please report the date of the last study directed procedure performed (e.g. biopsy, 
resection, excision, radiation therapy). 
 
This study will be monitored by the Abbreviated Clinical Data System (CDUS) Version 3.0 
CDUS data will be submitted quarterly to CTEP by electronic means. 

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11.0 
STATISTICAL CONSIDERATIONS   
 
This is two-stage single cohort phase II clinical trial to access efficacy and toxicity of 
weekly chemotherapy (CT) and radiation (RT) in patients with locally advanced vulvar 
cancer (T3 or T4, N0 – N3, M0) not amenable to surgery. Consequently, randomization is 
not employed. The GOG Statistical and Data Center will facilitate centralized registration 
via a web registration tool from within the GOG’s website.  
 
11.1 
Study Objectives  
 
This study will evaluate endpoints that are specific to clinical and translational 
research (TR) objectives. 
 
11.11 Primary objective 
 
To determine the efficacy of cisplatin, gemcitabine, and IMRT in 
achieving a complete pathologic response (pCR). 
 
11.12 Secondary objectives 
 
11.121 To determine the efficacy of cisplatin, gemcitabine, and IMRT in 
achieving a complete clinical response  
 
11.122 To assess treatment toxicity in the study population 
 
11.123 To estimate progression-free survival (PFS) in the study population 
 
11.2 
Endpoints and Data Elements 
 
Primary endpoint is complete partologic response (pCR), defined among patients 
who experienced a complete clinical resonse and had a negative local core biopsy 
or FNA.  In addition, the following endpoints and data elements will be used to 
evaluate primary, secondary, and/or translational research objectives: 
 
11.21 Complete clinical response (cPR) is defined as no clinical/radiographic 
evidence of primary disease (vulvar or groin) following chemo-radiation 
therapy. 
 
11.22 Incidence and severity of adverse effects as assessed by CTCAE v4.0 
 
11.23 Progression free survival (PFS)   
 
11.24 Site(s) of recurrence/relapse (local, loco-regional or distant) 
 

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11.25 Regarding treatment compliance: treatment span, incidence and duration 
of treatment delay, reasons for delays, chemotherapy dose, radiation dose 
and reasons for dose level reductions 
 
11.26  Baseline patient characteristics: age, performance status, race and ethnicity 
 
11.27  Disease characteristics: clinical tumor size, cell type, FIGO stage, grade, 
TNM classification, time from primary diagnosis to study entry, location 
of lesion(s) 
 
11.3 
Accrual and Study Duration   
 
Accrual estimates and study duration are based on GOG-0205 experience.  
 
11.31 Anticipated monthly accrual is 1 to 2 patients.  
 
11.32 Accrual objective is at most 52 evaluable patients 
 
11.34   Anticipated active accrual period is 30 to 48 months. 
 
11.33 Post-accrual follow-up period is 6 months. 
 
11.4 
Study Design and Sample Size Justification. 
The optimal design selected for this study seeks to: a) minimize the number of 
patients treated and b) estimate efficacy with reasonable precision.  However, in 
multi-center clinical trial, stopping accrual at the exact minimum sample size is 
logistically challenging, if not impossible.  As a result it makes sense to adopt a 
flexible design, with nearly optimal decision rules across a range of sample sizes. 
In particular, this study will utilize a “flexible two-stage” design with “nearly 
optimal” decision rules according to Chen (1998) 19 
 
Historical data and design parameters were selected based on GOG-0205, a 
recently concluded phase II trial of CIS-RT in patients with previously untreated 
squamous cell carcinoma of the vulva. There were 61 women on GOG-0205, 
accrued over a period of 4 years. Three patients were later deemed ineligible due 
to:  improper pre-protocol therapy (N=1); inadequate pathology (N=2) 
 
At the conclusion of primary chemo-radiation, the estimated complete clinical and 
pathologic response rates (on GOG 0205) were 64% and 50% respectively. In 
follow-up, 35 women are alive (4 with evidence of recurrent/persistent vulva 
cancer) and 23 have died as a result of:  cancer (N=18); treatment-related 
complications (N=1), other causes (N=3), undetermined (N=1).  The 12 month 
PFS is estimated at 70% (Figure 11.4.1)  

NCI Protocol #: GOG-0279  
Version Date:  07/21/2016 
 
- 48 - 
 
Figure 11.4.1 Progression free survival among GOG-0205 cohort 
 
This current study seeks to improve on the results of GOG -0205. Treatment 
efficacy will be access based on the relative frequency of complete pathologic 
response (pCR). The null hypothesis provides the range of pCR probability 
associated with an insufficiently active treatment and the alternative hypothesis 
provides the probability range associated with an active treatment: HO: pCR ≤ 
0.50 versus HA: pCR ≥ 0.70 
 
The target size for the first stage of accrual is 24 evaluable patients. If more than 
12 (i.e. >12 out of 24) patients experienced a pCR, accrual to the second stage 
will be initiated. Otherwise, accrual will be stopped and the treatment regimen 
will be deemed as clinically uninteresting.  If the study advances to the second 
stage, then an overall study accrual of 49 eligible and evaluable patients will be 
targeted. If no more than 28 (i.e. ≤ 28 out of 49) patients experienced a pCR, the 
regimen will be considered clinically uninteresting.  
The preceding set of decision rules are based on a fixed target size. Since 
accruing the target size exactly is administratively challenging, especially for 
multi-center clinical trials, in practice the first and second (if needed) stage 
accrual sizes will be permitted to range from 20 to 27 and 45 to 52 eligible and 
evaluable patients respectively. Table 11.4.2 provides specific stopping rules 
across the allowed sample size range for each stage of accrual. 
 
 
Proportion 
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Months
0
12
24
36
48
   Treatment
Censored
 Event
Total
   CIS-RT
  31
  27
  58

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Version Date:  07/21/2016 
 
- 49 - 
Accrual 
* pCR (Sample size) 
Stage Target 
Limits 
1 
24 
20 – 27 10(20 – 21), 11(22 – 23) , 12(24), 13(25 – 26), 14(27) 
2 
49 
45 - 52 
28(45 - 51), 29(52) 
*Maximum number of pCR to reject HA 
 
Table 11.4.2: Decision / stopping rules by stage of accrual 
 
Design characteristics: if the true probability of pCR is equal to 50% (HO), these 
decision rules (table 11.4.2) limit the average probability of designating the 
treatment as active to 10% (i.e. probability of type I error = 0.10) and have an 
average probability of stopping after completing the first stage of accrual equal to 
58%.  On the other hand, if the true probability of pCR is 70% (HA) then the 
average probability of correctly classifying the treatment as active is 93% (i.e. 
probability of type II error = 0.070). These statistical probabilities are average 
probabilities computed from individual probabilities averaged over all permitted 
accrual combinations and assuming each combination is equally likely.  Limited 
investigations have indicated that the false positive and false negative errors are 
fairly insensitive to variations in the true probability distribution of accrual 
combinations 20. Figure 11.4.3 shows the average probability of early termination 
(solid line) and average total probability of rejecting the treatment (broken line) as 
a function of the true probability of complete pathologic response (pCR). 
 

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Version Date:  07/21/2016 
 
- 50 - 
 
Figure 11.4.3 
 
It is important to emphasize this design choice encompasses characteristics 
similar to an Simon’s optimal two-stage design 21 (see table 11.4.4) and also 
allows for sample size flexibility.  
 
Design 
Targeted Accrual (Rejection Boundary) 
APET 
        Error  
Stage I 
Stage II 
Type I  Type II 
Rigid (Simon’s) 21 
24 (≤13) 
49 (≤ 28) 
0.729 
9.6% 
9.2% 
Flexible  
24 (≤12) 
49 (≤ 28) 
0.579 
10.0% 
7.0% 
 
Table 11.4.4 
 
11.5 
Analysis Plan  
Only those patients who are deemed "ineligible" or who receive no therapy will 
be excluded from the analysis. All patients who receive any therapy will be 
evaluated for both treatment efficacy and toxicity.  
 
Evaluation of Primary Endpoints  
Efficacy will be evaluated as the frequency of complete clinical and 
pathologic response after primary therapy. Only those patients who are 
deemed ineligible or receive no therapy or refused all radiation therapy 
APET/ATPRT
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
pCR
0.45
0.50
0.55
0.60
0.65
0.70
0.75

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- 51 - 
without any medical contraindication will be considered inevaluable for 
response.  All patients who receive any therapy will be evaluated for 
toxicity.  
 
While on occasion, circumstances may prevent the determination of treatment 
efficacy, such patients will be included in the analysis and labeled as "unknown".  
This category will be listed and be reflected in the calculation of the response rate. 
The probability of attaining a complete pathologic response will be estimated.   
 
Evaluation of PFS and OS 
Product-limit estimates according to the method of Kaplan and Meier will be 
calculated to assess duration PFS and OS among the entire study cohort and by 
response status. 
 
Evaluation of Site(s) of Recurrence  
Site(s) of first disease recurrence will be classified as: local (vagina or vulva), loco-
regional (within the pelvic) or distant and tabulated by response status.  
 
 
Toxicity    
Maximum grade of treatment related adverse effect will be tabulated based CTCAE v4.0 
grading system  
 
 
11.6 
Study Monitoring, Data Quality Control and Semi-annual Reports 
The GOG SDC will be responsible for, conducting centralized patient registration, 
study monitoring, data collection, storage and analysis. To assure the best possible 
data quality, the study statistician in collaboration the data manager/coordinator 
(DM) will execute regular data checks. Inconsistencies and errors will be queried 
and sites will notify the DM upon resolution. In turn the DM will repeat data 
checks to make certain queried issues were indeed resolved. Every effort will be 
made to resolve outstanding queries promptly. Unresolved queries will be 
documented and cited in a comment field of the study scientific table.   
 
Case report forms (CRFs) will be reviewed before each semi-annual meeting and 
will also be reviewed by the Study Chairperson in conjunction with the Statistical 
and Data Center. The purpose of these reviews is to access protocol compliance 
and possibly make recommendations aimed at improving study compliance. In 
some instances, because of unexpectedly severe toxicity, the Statistical and Data 
Center may elect, after consultation with the Study Chairperson and the Medical 
Oncology Committee, to recommend early closure of a study. 
 
After data checks, study chair (co-chair) reviews and data updates, a locked 
dataset void of protected patient information will be saved using standard GOG 
SDC dataset achieving convention. 
   
 
 
Reports will be generated from the most recent locked information by the study 
statistician for inclusion into the GOG’s Semi-annual Statistical Report (GOG 

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SR).  The study SR will comprise of accrual (and patient accession) information, 
distribution of baseline traits, treatment compliance, and patient safety (adverse 
events) data, thus providing a mechanism for reviewing and monitoring study 
progress and for conducting a study with optimal efficiency. 
  
All serious (SAE) and unexpected adverse events regardless of attribution will be 
communicated promptly to the study chair, and any regulatory agencies as 
mandated in the protocol. These reports are reviewed within two working days for 
consideration of investigator notification, amendment, or immediate study 
suspension.  
 
Toxicity information will also be reviewed by the GOG Safety Review 
Committee (SRC) at each semi-annual meeting during the period for which 
patients are on study (being treated). The goal of the SRC is to review the AE 
data, including all new SAE reports (from ongoing GOG studies) submitted 
between consecutive GOG business meetings held in January and July each year. 
(04/21/2014) 
 
In addition, in the event of more than one treatment-related death that occur on-
study, or more than TWO identical unexpected treatment-related non-hematologic 
grade 4 toxicities, centralized registration and accrual will be suspended pending 
further review.  All participating institutions will then receive notification of the 
toxicities and reason for study suspension.  Under these circumstances, accrual 
cannot be re-activated until the study is reviewed by the GOG Data and Safety 
Monitoring Board.   However, patients currently receiving treatment may 
continue to receive treatment in accordance protocol guidelines at the discretion 
of their physicians, unless directed otherwise.  
 
As this is a two-stage group-wide phase II protocol, the initial overall review of toxicity 
is usually performed after completion of the first stage of accrual, at which point accrual 
is generally suspended pending formal analysis of response and toxicity. 
 
 
 

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11.7 
Planned Minority Inclusion 
The following table provides race and ethnicity distribution anticipated for this 
trial (based on GOG-0205).  
 
Accrual Targets ( N = 49) 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
     2 
+ 
0 
= 
2 
Not Hispanic or Latino 
47 
+ 
0 
= 
47 
Ethnic Category: Total of all subjects 
49 
(A1) 
+ 
   0   
(B1) 
= 
   49  
(C1) 
Racial Category 
 
American Indian or Alaskan Native 
2 
+ 
0 
= 
   2 
Asian 
1 
+ 
0 
= 
    1 
Black or African American 
3 
+ 
0 
= 
   3 
Native Hawaiian or other Pacific Islander 
1 
+ 
0 
= 
    1 
White 
        42 
+ 
0 
= 
 42 
Racial Category: Total of all subjects 
  49       
(A2) 
+ 
0  
(B2) 
= 
 49  
(C2) 
 
(A1 = A2)  
(B1 = B2)  
(C1 = C2) 
 
 

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12.0 
BIBLIOGRAPHY   
 
1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer Statistics, 2008. CA 
Cancer J Clin. 2008;58:71-96. 
 
2. Moore DH, Thomas GM, Montana GS, Saxer A, Gallup DG, Olt G. Preoperative 
chemoradiation for advanced vulvar carcinoma: a phase II study of the Gynecologic 
Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42(1):79-85. 
 
3. Moore D, Ali S, Barnes M, et al. A phase II trial of radiation therapy and weekly 
cisplatin chemotherapy for the treatment of locally advanced squamous cell carcinoma 
of the vulva: a Gynecologic Oncology Group study. Gynecologic Oncology. 
2011;120:s2-s133.  Abstract 1. 
 
4. Beriwal S, Heron DE, Kim H, King G, Shogan J, Bahri S, et al. Intensity-modulated 
radiotherapy for the treatment of vulvar carcinoma: a comparative dosimetric study with 
early clinical outcome. Int J Radiat Oncol Biol Phys. 2006;64:1395-1400. 
 
5. Huang P, Plunkett W. Induction of apoptosis by gemcitabine. Semin Oncol. 
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6. Hertel LW, BoderGB, Kroin JS, et al. Evaluation of antitumor activity of gemcitabine 
(2’,2’-difluoro-2’-deoxycytidine). Cancer Res. 1990;50:4417-4422. 
 
7. Mose S, Karapetian M, Juling-Pohlit L, et al. The intesification of the radiotherapeutic 
effect on HeLa cells by gemcitabine. Strahlenther Onkol. 1999;75(2):78-83. 
 
8. Candelaria M, Garcia-Arias A, Cetina L, et al. Radiosensitizers in cervical 
cancer:cisplatin and beyond. Radiat Oncol. 2006; 1:15. 
 
9. Peters GJ, Bergman AM, Ruiz van Haperen VWT, et al. Interaction between cisplatin 
adn gemcitabine in vitro and in vivo. Semin Oncol. 1995;22:72-79. 
 
10. Thodossiou C, Cook JA, Fisher J, et al. Interaction of gemcitabine with paclitaxel and 
cisplatin in human tumor cell lines. Int J Oncol. 1998;12:825-832. 
 
11. Rose PG, DeGees K, McMeekin S, Fusco N. A phase I study of gemcitabine followed 
by cisplatin concurrent with whole pelvic radiation therapy in locally advanced cervical 
cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;107:274-279. 
 
12. Zarba JJ, Jaremtchuk AV, Gonzales Jazey P, et al. A phase I/II study of weekly cisplatin 
and gemcitabine with concurrent radiotherapy in locally advanced cervical cancer. Ann 
Oncol. 2003;14:1285-1290. 
 

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13. Umanzor J, Aguiluz M, Pineda C, et al. Concurrent cisplatin/gemcitabine aling with 
radiotherapy in locally advanced cervical carcinoma: a phase II trial. Gynecol Oncol. 
2006;100:70-75. 
 
14. Duenas-Gonzales A, Cetina-Perex L, Lopez-Graniel C, et al.  Pathologic response and 
toxity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine 
in cervical cancer: a randomized phase II study. Int J Radiat oncol biol Phys. 
2005;61:817-823. 
 
15. Duenas-Gonzales A, Zabra JJ, Patel F, Alcedo JC, et al.  Phase II open-label randomized 
study comparing concurrent gemcitabine plus cisplatin and radiation followed by 
adjuvant cemcitabine and cisplatin versus concurrent cisplatin and radiation in patients 
with stage Iib to IVA carcinoma of the cervix. JCO. 2011. 
 
16. Monk BJ, Burger RA, Lin F, Parham G, Vasilex SA, Wilczynski SP.  Prognostic 
significance of human papillomavirus DNA in vulvar carcinoma. Obstet Gynecol. 
1995;85(5 Pt 1):709-715. 
 
17. Toki T, Kurman RJ, Park JS, Kessis T, Daniel RW, Shah KV.  Probable 
nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a 
clinicopathologic study using in situ hydridization and polymerase chain reaction. Int. J 
Gynecol Pathol. 1991;10(2):107-125. 
 
18. Kim/Beriwal. ASTRO 2011. 
 
19. Chen TT, NG T. Optimal flexible designs in phase II clinical trials. Statistics in 
Medicine. 1998;17:2301-2312. 
 
20. Sill M. GOG Statistical and Data Center, Buffalo NY 14263. Unpublished work. 2011. 
 
21. Simon R. Optimal 2-stage design for phase II trials. Controlled Clinical Trials. 
1989;10:1-10. 
 
 
 
 
 
 
 
 

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APPENDIX I 
 
TNM and International Federation of Gynecology and Obstetrics (FIGO) 
Staging Systems for Vulvar Carcinoma 
 
The TNM staging system of the American Joint Committee on Cancer (AJCC) and the 
International Union Against Cancer (UICC) for carcinoma of the vulva is recommended and is 
shown below.1, 2 Comparison with FIGO staging is also shown.3, 4 
According to AJCC/UICC convention, the designation “T” refers to a primary tumor that has not 
been previously treated.  The symbol “p” refers to the pathologic classification of the TNM, as 
opposed to the clinical classification, and is based on gross and microscopic examination.  pT 
entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category, 
pN entails removal of nodes adequate to validate lymph node metastasis, and pM implies 
microscopic examination of distant lesions.  Clinical classification (cTNM) is usually carried out 
by the referring physician before treatment during initial evaluation of the patient or when 
pathologic classification is not possible. 
Pathologic staging is usually performed after surgical resection of the primary tumor.  Pathologic 
staging depends on pathologic documentation of the anatomic extent of disease, whether or not 
the primary tumor has been completely removed.  If a biopsied tumor is not resected for any 
reason (eg, when technically infeasible) and if the highest T and N categories or the M1 category 
of the tumor can be confirmed microscopically, the criteria for pathologic classification and 
staging have been satisfied without total removal of the primary cancer. 
TNM and FIGO Staging Systems for Vulvar Carcinoma 
 
Primary Tumor (T) 
TNM Categories 
FIGO Stages 
TX 
 
 
 
Primary tumor cannot be assessed 
TO 
 
 
 
No evidence of primary tumor 
Tis 
 
 
 
Carcinoma in situ (preinvasive carcinoma) 
T1a 
IA 
 
 
Lesions 2cm or less in size, confined to the vulva or 
perineum and with stromal invasion 1.0 mm or less 
T1b 
IB 
 
 
Lesions more than 2 cm in size or any size with 
stromal invasion more than 1.0 mm, confined to the 
vulva or perineum 
T2 
II 
 
 
Tumor of any size with extension to adjacent 
perineal structures (lower/distal 1/3 urethra, 
lower/distal 1/3 vagina, anal involvement) 
T3 
IVA 
 
Tumor of any size with extension to any of the 
following:  upper/proximal 2/3 of urethra, 
upper/proximal 2/3 vagina, bladder mucosa, rectal 
mucosa, or fixed to pelvic bone 
 
Note:  The depth of invasions is defined as the measurement of the tumor from the epithelial-
stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. 
 
 

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Regional Lymph Nodes (N) 
NX 
Regional lymph nodes cannot be assessed 
N0 
No regional lymph node metastasis 
N1 
 
 
 
 
One or two regional lymph nodes with the 
following features 
 
N1a 
IIIA 
One or two lymph node metastasis each 5 mm or 
less 
N1b 
IIIA 
One lymph node metastasis 5 mm or greater 
N2 
IIIB 
 
Regional lymph nodes metastasis with the following 
features 
 
N2a 
IIIB 
 
Three or more lymph node metastases each less 
than 5 mm 
N2b 
IIIB 
 
Two or more lymph node metastases 5 mm or 
greater 
N2c 
IIIC 
 
Lymph node metastasis with extracapsular spread 
N3 
IVA 
 
Fixed or ulcerated regional lymph node metastasis 
 
Distant Metastasis (M) 
M0 
 
 
No distant metastasis 
M1 
IVB 
 
Distant metastasis (including pelvic lymph node 
metastasis) 
 
Anatomic Stage/prognostic Groups 
Stage 0 
Tis 
 
N0 
 
M0 
Stage I 
T1 
 
N0 
 
M0 
Stage IA 
T1a 
 
N0 
 
M0 
Stage IB 
T1b 
 
N0 
 
M0 
Stage II 
T2 
 
N0 
 
M0 
Stage IIIA 
T1, T2  
N1a, N1b 
M0 
Stage IIIB 
T1, T2  
N2a, N2b 
M0 
Stage IIIC 
T1, T2  
N2c 
 
M0 
Stage IVA 
T1, T2  
N3 
 
M0 
 
T3 
 
Any N  
M0 
Stage IVB 
Any T  
Any N  
M1 
 
1 Vulva.  In:  Edge SB, Byrd DR, Carducci MA, Compton CC, eds.  AJCC Cancer Staging 
Manual.  7th ed.  New York, NY: Springer; 2009 
2 Sobin LH, Gospodarowicz M, Wittekind Ch, eds.  UICC TNM Classification of 
Malignant Tumours.  7th ed.  New York, NY: Wiley-Liss; in press. 
3 Pecorelli S, Denny L, Ngan H et al.  Revised FIGO staging for carcinoma of the vulva, 
cervix, and endometrium.  Int J Gynecol Obstet.  2009; 105: 103-104. 
4 Hacker N.  Revised FIGO staging for carcinoma of the vulva nt J Gynecol Obstet.  2009; 
105: 105-106.

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APPENDIX II 
GOG General Chemotherapy Guidelines (08/15/2016) 
 
• For 21 or 28 day cycles, a patient will be permitted to have a new cycle of 
chemotherapy delayed up to 7 days (without this being considered to be a 
protocol violation) for major life events (e.g., serious illness in a family member, 
major holiday, vacation which is unable to be re-scheduled).  Documentation to 
justify this decision should be provided. 
• It will be acceptable for individual chemotherapy doses to be delivered within a 
“24-hour window before and after the protocol-defined date” for “Day 1” 
treatment of 21 or 28 day cycles.  If the treatment due date is a Friday, and the 
patient cannot be treated on that Friday, then the window for treatment would 
include the Thursday (1 day earlier than due) through the Monday (day 3 past 
due). 
• For weekly regimens, it will be acceptable for individual chemotherapy doses to 
be delivered within a “24-hour window,” for example; “Day 8 chemotherapy” can 
be delivered on Day 7, Day 8, or Day 9 and “Day 15 chemotherapy” can be given 
on Day 14, Day 15, or Day 16. 
• Chemotherapy doses can be “rounded” according to institutional standards 
without being considered a protocol violation (most institutions use a rule of 
approximately +/- 5% of the calculated dose). 
• Chemotherapy doses are required to be recalculated if the patient has a weight 
change of greater than or equal to 10%.  Patients are permitted to have 
chemotherapy doses recalculated for < 10% weight changes. 

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APPENDIX III 
SENTINAL NODE BIOPSY FOR VULVAR CANCER 
 
Purpose  
 
1) Histologic evaluation for nodal metastasis.  
2) Surgical-pathologic staging of vulvar cancer.  
3) Provide guidelines for subsequent therapy.  
 
Indications  
 
1) Primary invasive cancer of the vulva.  
 
Contraindications  
1) Poor surgical risk  
2) Grossly positive groin nodes  
 
Content of the procedure  
Prior to surgery, lymphoscintigraphy is performed by injecting 
radionuclide intradermally at the leading border of the primary tumor (the 
border closest to the groin(s) or scar site if an excisional biopsy was done). 
For midline tumors, inject on both sides of the tumor. Anatomic markers 
should be placed on the symphasis pubis and anterior superior iliac spines. 
The patient is immediately scanned. The skin over the SN can be marked 
with an indelible marker. Transmission scans, which show the outline of 
the body, should be performed if possible. Following induction of 
anesthesia, the hand-held gamma counter is used to try to identify the 
sentinel node transcutaneously. The skin over the sentinel node is marked. 
Intradermal injection of isosulfan or methylene blue is made at the leading 
edge of the primary tumor (the border closest to the groin(s) or scar site if 
an excisional biopsy was done). The skin incision is made approximately 5 
minutes following the injection of isosulfan blue. The hand-held gamma 
counter may assist in the localization of the sentinel node. The sentinel 
node is identified and labeled.  
 
ADVERSE EFFECTS THAT MAY BE ASSOCIATED WITH AN UNEVENTFUL PROCEDURE  
 
SYSTEM  
 
 
 
 
 
 
GRADE (up to and including)  
 
Hematopoietic 
2  
Genitourinary  
1  
Gastrointestinal 
1  
Hepatic  
1  
Pulmonary  
1  
Cardiovascular 
1  
Peripheral Neurologic 
1  
Central Neurologic 
1  
Cutaneous  
2  
Lymphatics 
1  
Fever  
2  
Allergic 
0 
 
 

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APPENDIX IV 
DEEP INGUINAL LYMPHADENECTOMY 
 
Purpose  
 
1)  Excisional biopsy of the deep inguinal or femoral lymph nodes for histologic 
evaluation and treatment in patients with invasive cancer of the vulva.  
 
Indications  
2) Primary invasive cancer of the vulva.  
 
Contraindications 
1)  Evidence of distant metastases or pelvic adenopathy  
2)  Significant medical problems that make the patient a poor surgical risk.  
Content of Procedures  
A superficial lymphadenectomy (See Superficial Inguinal Lymphadenectomy) 
has already been performed at the same setting. Any incision adequate for 
exposure may be used. During the previous superficial groin node dissection, the 
cribriform fascia over the fossa ovalis should have been preserved. The fascia 
covering the sartorius muscle should be reflected to ensure total removal of the 
lymph nodes in the femoral triangle. The femoral artery should be identified and 
the dissection carried along the artery until all lymphatic tissue is removed. The 
femoral nerve should be preserved. The femoral vein and saphenous vein should 
be identified and the lymphatic dissection continued caudad until the saphenous 
vein can be adequately mobilized. At the discretion of the surgeon, the 
saphenous vein may be doubly ligated near the sapheno-femoral junction and a 
segment removed with the node bearing tissue of it may be spared by dividing 
this tissue over the saphenous vein. Dissection continues to removal of all 
lymphatic tissue laterally to the sartorius and medially to the adductor longus 
muscles. At the discretion of the surgeon, the sartorius muscle is then mobilized, 
transected at its insertion with electrocautery, transplanted over the femoral 
vessels and sutured to the inguinal ligament with permanent suture. Suction 
drains may be placed bilaterally followed by closure of the subcutaneous tissues 
and skin.  
  
ADVERSE EFFECTS THAT MAY BE ASSOCIATED WITH AN UNEVENTFUL PROCEDURE  
 
SYSTEM 
 GRADE (up to and including)  
 
Hematopoietic  
 
 
 
 
 
 
2  
Genitourinary  
 
 
 
 
 
 
1  
Gastrointestinal 
 
 
 
 
 
 
1  
Hepatic 
 
 
 
 
 
 
 
1  
Pulmonary 
 
 
 
 
 
 
 
1  
Cardiovascular 
 
 
 
 
 
 
1  
Peripheral Neurologic 
  
 
 
 
 
1  
Central Neurologic 
 
 
 
 
 
 
1  
Cutaneous 
  
 
 
 
 
2  
Lymphatics   
 
 
 
 
 
 
1  
Fever  
  
 
 
 
 
2  
Allergic 
 
 
 
 
 
 
 
0 

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APPENDIX V 
SUPERFICIAL INGUINAL LYMPHADENECTOMY 
 
Purpose  
 
1) Excisional biopsy of the superficial inguinal lymph nodes for histologic 
study in patients with early, invasive squamous cell carcinoma of the vulva.  
 
Indications  
1)  Primary invasive cancer of the vulva.  
 
Contraindications  
1) More advanced stages of clinical disease.  
2)  Suspicious or grossly positive inguinal adenopathy.  
 
Content of Procedure  
Superficial inguinal lymphadenectomy may be approached through groin 
incisions 1-2 cm below and parallel to Poupart’s ligament or through a vertical 
incision. The superficial inguinal fat pad is removed by dissecting the node-
bearing fatty areolar tissue which lies deep to Camper’s fascia, superficial to 
Colles’s fascia, the cribriform fascia and the fascia lata. The cephalad extent of 
dissection is Poupart’s ligament; the medial extent is the medial surface of the 
adductor longus muscle; the lateral extent is the medical border of the sartorius 
muscle; and the distal extent is approximately 6 cms distal to Poupart’s 
ligament. The dissection may proceed from medial to lateral at the surgeon’s 
discretion. Care should be taken to preserve the cribriform fascia over the fossa 
ovalis. The operative field may be drained with suction drains. Closure of the 
subcutaneous tissues and skin may be accomplished at the surgeon’s discretion.  
 
ADVERSE EFFECTS THAT MAY BE ASSOCIATED WITH AN UNEVENTFUL PROCEDURE  
 
SYSTEM 
 
 
 
 
 
 
 
 GRADE (up to and including)  
 
Hematopoietic  
 
 
 
 
 
 
 
2  
Genitourinary  
 
 
 
 
 
 
 
1  
Gastrointestinal 
 
 
 
 
 
 
 
1  
Hepatic 
 
 
 
 
 
 
 
 
1  
Pulmonary 
 
 
 
 
 
 
 
 
1  
Cardiovascular 
 
 
 
 
 
 
 
1  
Peripheral Neurologic  
 
 
 
 
 
 
1  
Central Neurologic 
 
 
 
 
 
 
 
1  
Cutaneous 
  
 
 
 
 
 
2  
Lymphatics 
 
 
 
 
 
 
 
 
1  
Fever 
  
 
 
 
 
 
2  
Allergic 
 
 
 
 
 
 
 
 
0