Clinical trial NCT05076942: Groningen International Study on Sentinel Nodes in Vulvar Cancer-III
Official title: Groningen International Study on Sentinel Nodes in Vulvar Cancer-III, a Prospective Phase II Treatment Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Vulvar Cancer
Sentinel Lymph Node
Lymph Node Metastases
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
name: NRG Oncology
First posted: 2021-10-13
Enrollment: 157
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: phase II treatment trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Groin recurrence rate
timeFrame: Within first 2 years after primary treatment
Secondary outcomes:
measure: Treatment related morbidity
timeFrame: First two years after primary treatment
measure: Quality of life as assessed using EORTC-QLQc30
timeFrame: First two year after primary treatment
measure: Quality of life-vulvar cancer specific, as assessed using VU34
timeFrame: First two year after primary treatment
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Duke Women's Cancer Care Raleigh
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Eindhoven
country: Netherlands
facility: Catharina Hospital Eindhoven
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
References: