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Groningen International Study on Sentinel Nodes in Vulvar Cancer-III

Phase 2
Recruiting
Conditions
Lymph Node Metastases
Vulvar Cancer
Sentinel Lymph Node
Interventions
Radiation: Radiotherapy combined with cisplatin
Registration Number
NCT05076942
Lead Sponsor
University Medical Center Groningen
Brief Summary

Vulvar cancer patients with SN-metastasis \> 2mm will receive chemoradiation instead of an inguinofemoral lymphadenectomy.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
157
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ChemoradiationRadiotherapy combined with cisplatinInguinofemoral 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
ChemoradiationCisplatinInguinofemoral 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
Primary Outcome Measures
NameTimeMethod
Groin recurrence rateWithin first 2 years after primary treatment

Groin recurrence in the groin with SN metastasis treated with chemoradiation

Secondary Outcome Measures
NameTimeMethod
Treatment related morbidityFirst two years after primary treatment

Short and longterm morbidty

Quality of life as assessed using EORTC-QLQc30First two year after primary treatment

Quality of life

Quality of life-vulvar cancer specific, as assessed using VU34First two year after primary treatment

Quality of life-vulvar cancer specific

Trial Locations

Locations (27)

Duke Women's Cancer Care Raleigh

🇺🇸

Raleigh, North Carolina, United States

Memorial Sloan Kettering Monmouth

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering Nassau

🇺🇸

Uniondale, New York, United States

Spectrum Health at Butterworth Campus

🇺🇸

Grand Rapids, Michigan, United States

Memorial Sloan Kettering Westchester

🇺🇸

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Basking Ridge

🇺🇸

Basking Ridge, New Jersey, United States

Nebraska Methodist Hospital

🇺🇸

Omaha, Nebraska, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

Memorial Sloan Kettering Commack

🇺🇸

Commack, New York, United States

Women and Infants Hospital

🇺🇸

Providence, Rhode Island, United States

Avera Cancer Institute

🇺🇸

Sioux Falls, South Dakota, United States

Radboud University Medical Center

🇳🇱

Nijmegen, Netherlands

Catharina Hospital Eindhoven

🇳🇱

Eindhoven, Netherlands

Leiden University Medical Center

🇳🇱

Leiden, Netherlands

University Medical Center Groningen

🇳🇱

Groningen, Netherlands

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

🇺🇸

Orange, California, United States

Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Munson Medical Center

🇺🇸

Traverse City, Michigan, United States

ProMedica Flower Hospital

🇺🇸

Sylvania, Ohio, United States

Memorial Sloan Kettering Bergen

🇺🇸

Montvale, New Jersey, United States

Women's Cancer Center of Nevada

🇺🇸

Las Vegas, Nevada, United States

Baystate Medical Center

🇺🇸

Springfield, Massachusetts, United States

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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