Groningen International Study on Sentinel Nodes in Vulvar Cancer-III

Study Overview
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Brief Summary
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Vulvar cancer patients with SN-metastasis > 2mm will receive chemoradiation instead of an inguinofemoral lymphadenectomy.

Detailed Description
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Rationale: Standard treatment of early stage vulvar cancer is a wide local excision of the primary tumor combined with the sentinel node (SN) procedure for the groins. An inguinofemoral lymphadenectomy (IFL) is only indicated in case of a positive SN. An IFL is associated with major morbidity, e.g. wound healing problems, lymphoceles, lymphedema of the legs and recurrent infections. GROINSS-V II investigated whether radiotherapy would be a safe alternative for IFL in case of SN metastasis. The results for radiotherapy in the group with metastasis ≤ 2mm are promising. This study also showed that for metastasis > 2mm, only radiotherapy was not efficient. The efficacy of treatment can be increased by adding chemotherapy or giving a higher dose of radiotherapy. GROINSS-V III will investigate this regimen. Objective: The primary objective of this study is to investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in early stage vulvar cancer patients with a macrometastasis (>2mm) and/or extracapsular extension in the SN. The secondary objective is to evaluate the short and long-term morbidity associated with the SN procedure and chemoradiation. Study design: Phase II treatment trial, with stopping rules for the incidence of groin recurrences. Study population: early-stage vulvar cancer patients with a metastasis > 2mm in their SN, or more than one metastasis ≤ 2mm. Intervention: Participants will be treated with chemoradiation, in a total dose of 56Gy to the involved site, combined with weekly cisplatin 40mg/m2 Main study parameters/endpoints: The primary endpoint is the groin recurrence rate in the first 2 years after primary treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: participants will be treated with chemoradiation during 5 weeks instead of surgical treatment. There is a risk that this treatment will not be as effective as surgical treatment, which may lead to more groin recurrences which are hard to treat. By continuously monitoring the groin recurrence rate the investigators will notice activation of the stopping rule as early as possible.

Official Title
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Groningen International Study on Sentinel Nodes in Vulvar Cancer-III, a Prospective Phase II Treatment Trial

Conditions
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Vulvar Cancer, Sentinel Lymph Node, Lymph Node Metastases

Intervention / Treatment
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* Radiation: Radiotherapy combined with cisplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmed primary SCC of the vulva T1 tumor, not encroaching urethra/vagina/anus Depth of invasion > 1mm Tumor diameter < 4cm Unifocal tumor No enlarged (>1.5cm) or suspicious inguinofemoral lymph nodes at imaging (CT/MRI/ultrasound) Possibility to obtain informed consent Metastatic sentinel lymph node; size of metastasis > 2mm and / or extracapsular extension, or Metastatic sentinel lymph node: more than 1 SN with metastasis ≤ 2mm Patients are able to understand requirements of study, provide written informed consent and comply with the study and follow-up procedures Adequate bone marrow, renal and liver function: Absolute neutrophil count ≥ 1.5 x 109 /L Platelet count ≥ 100 x 109 /L Creatinine clearance ≥ 40 ml/min measured by the Cockroft Gault formula Total bilirubin < 1.25 x ULN Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale (Appendix A) Age 18 years or older Life expectancy of ≥ 12 weeks Written informed consent Exclusion Criteria: Inoperable tumors and tumors > 4cm Multifocal tumors Tumors with other pathology than squamous cell carcinoma Patients with enlarged / suspicious lymph nodes which are proven metastatic after fine needle aspiration cytology No other carcinomas, other than basal cell carcinomas, within last 5 years History of pelvic radiotherapy History of any infection requiring hospitalization or antibiotics within 2 weeks before enrollment Pregnant female or nursing mother Desire to become pregnant Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids Unstable angina, myocardial infarction, cerebrovascular accident, > Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure (see Appendix B) within 6 months before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: phase II treatment trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemoradiation<br>Inguinofemoral radiotherapy (48-50 Gy in 1.8 Gy daily fractions, with a boost dose to the involved inguinal site for a total equivalent dose of 56 Gy over 5-6 weeks, preferably with simultaneous integrated boost technique) combined with weekly cisplatin 40 mg/m2 intravenously on days 1, 8, 15, 22 and 29 | Radiation: Radiotherapy combined with cisplatin<br>* Inguinofemoral radiotherapy combined with weekly cisplatin<br>* Other names: chemotherapy;Drug: Cisplatin<br>* Inguinofemoral radiotherapy combined with weekly cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Groin recurrence rate | Groin recurrence in the groin with SN metastasis treated with chemoradiation | Within first 2 years after primary treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related morbidity | Short and longterm morbidty | First two years after primary treatment | 
| Quality of life as assessed using EORTC-QLQc30 | Quality of life | First two year after primary treatment | 
| Quality of life-vulvar cancer specific, as assessed using VU34 | Quality of life-vulvar cancer specific | First two year after primary treatment |