Groningen International Study on Sentinel Nodes in Vulvar Cancer-III

Vulvar Cancer Clinical Trial

— GROINSS-VIII  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05076942
• Other study ID #: 2016-00601
• Secondary ID: NRG-GY024
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2021
• Est. completion date: January 1, 2029

Study information

• Verified date: July 2023
• Source: University Medical Center Groningen
• Contact: Maaike H Oonk, MD PhD
• Phone: +31-50-3613000
• Email: m.h.m.oonk[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 157
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymph Node Metastases
• Lymphatic Metastasis
• Sentinel Lymph Node
• Vulvar Cancer
• Vulvar Neoplasms

Intervention

Radiation:
• Radiotherapy combined with cisplatin
Inguinofemoral radiotherapy combined with weekly cisplatin

Drug:
• Cisplatin
Inguinofemoral radiotherapy combined with weekly cisplatin

Locations

Country	Name	City	State
Netherlands	Catharina Hospital Eindhoven	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Radboud University Medical Center	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Duke University Medical Center	Durham	North Carolina
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Baystate Medical Center	Springfield	Massachusetts
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	Dutch Cancer Society, NRG Oncology

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Groin recurrence rate	Groin recurrence in the groin with SN metastasis treated with chemoradiation	Within first 2 years after primary treatment
Secondary	Treatment related morbidity	Short and longterm morbidty	First two years after primary treatment
Secondary	Quality of life as assessed using EORTC-QLQc30	Quality of life	First two year after primary treatment
Secondary	Quality of life-vulvar cancer specific, as assessed using VU34	Quality of life-vulvar cancer specific	First two year after primary treatment