GROINSS-VIII: Groningen International Study on Sentinel Nodes in Vulvar Cancer-III

• Sponsor: University Medical Center Groningen (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05076942
• Collaborator: Dutch Cancer Society (Other)
• Enrollment: 157
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 96
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Vulvar Cancer; Sentinel Lymph Node; Lymph Node Metastases	Radiation: Radiotherapy combined with cisplatin; Drug: Cisplatin	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: phase II treatment trialphase II treatment trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Groningen International Study on Sentinel Nodes in Vulvar Cancer-III, a Prospective Phase II Treatment Trial
• Actual Study Start Date: Jan 1, 2021
• Anticipated Primary Completion Date: Jan 1, 2028
• Anticipated Study Completion Date: Jan 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemoradiation 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; Inguinofemoral radiotherapy combined with weekly cisplatin; Other Names: chemotherapy ; Drug: Cisplatin; Inguinofemoral radiotherapy combined with weekly cisplatin

Outcome Measures

Primary Outcome Measures

1. Groin recurrence rate [Within first 2 years after primary treatment]

   Groin recurrence in the groin with SN metastasis treated with chemoradiation

Secondary Outcome Measures

1. Treatment related morbidity [First two years after primary treatment]

   Short and longterm morbidty

2. Quality of life as assessed using EORTC-QLQc30 [First two year after primary treatment]

   Quality of life

3. Quality of life-vulvar cancer specific, as assessed using VU34 [First two year after primary treatment]

   Quality of life-vulvar cancer specific

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Medical Center Groningen	Groningen		Netherlands	9712RB

Sponsors and Collaborators

• University Medical Center Groningen
• Dutch Cancer Society

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maaike Oonk, Principle Investigator, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT05076942
• Other Study ID Numbers: 2016-00601
• First Posted: Oct 13, 2021
• Last Update Posted: Oct 13, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Vulvar Neoplasms; Lymphatic Metastasis; Cisplatin

Study Results

No Results Posted as of Oct 13, 2021