Locally Advanced Vulvar Carcinoma, Squamous Cell Carcinoma of the Vulva
Conditions
Brief summary
A phase 2 randomised controlled trial will be performed in which the efficacy and safety of standard treatment (primary chemoradiation; consisting of 64.5 Gy in 30 fractions of external beam radiotherapy with weekly cisplatin for six weeks) and experimental treatment (NACT; consisting of carboplatin and paclitaxel in a 3-weekly scheme) will be compared in 98 patients with LAVC, registered from eight national medical centres.
Interventions
Paclitaxel 175 mg/m2, followed by carboplatin 5 area under the curve (AUC). This will be administered in a 3-weekly scheme.
COMBINATION_PRODUCTChemoradiation
According to standard treatment.
Sponsors
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Woman ≥ 18 years * Signed and written informed consent. * Histologically-confirmed primary or recurrent squamous cell carcinoma vulvar cancer FIGO stage Ib - IVa, T1b or higher, any N, M0. * Local tumour through which the size or localization implies requirement of treatment through primary chemoradiation or surgery consisting of extensive surgery (meaning surgery damaging pelvic organs or exenterative surgery). This can imply; * T1b or larger tumour with (irresectable) groin metastases * T1b or larger tumour with a close relationship to and/or involvement of the urethra or anal sphincter * World Health Organization performance status of 0-2 * Adequate haematological function defined by platelet count \>100x10E9/L, absolute leukocyte \>3X10E9/L or neutrophil count (ANC) \>1.5x10E9/L, and hemoglobin \>6.0 mmol/L * Adequate hepatic function defined by a total bilirubin level ≤1.5x the upper limit of normal (ULN) range and ASAT and ALAT levels ≤2.5x ULN for all subjects * Adequate renal function defined by an estimated creatinine clearance ≥50mL/min according to the Cockroft-Gault formula (or local institutional standard method) * Beta HCG level of 14 mIU/mL or below for women of childbearing potential * Highly effective contraception for patients if the risk of conception exists
Exclusion criteria
* Patients with highly suspicious or positive metastases to the pelvic lymph nodes \* Patients eligible for radical local excision without involvement of other organs * Any psychiatric condition that would prohibit the understanding or rendering of informed consent * Prior radiotherapy to the pelvis or groin area limiting full dose chemoradiation according to protocol * Existing neuropathy which will hinder the intake of chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Loco-regional control after 24 months per completed treatment including salvage treatment | 24 months after completed treatment | Proportion of patients free from local-regional progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival | 24 months after completed treatment | — |
| Patterns of recurrence of disease | 24 months after completed treatment | Type of recurrence after treatment: local, regional or distant recurrence |
| Overall survival | 24 months after completed treatment | — |
| Disease-related treatment failure | 24 months after completed treatment | Patients without an event will be censored at their last date of contact. The Kaplan-Meier method will be used to estimate freedom from disease-related failure. Difference between the two main treatment arms, NACT vs. chemotherapy, will be tested using a log-rank test. Incidences of disease-related failure will be reported based on the Kaplan-Meier estimates, together with confidence intervals for the hazard ratio using both 90 and 95% confidence levels. |
| Prevention of trimodal treatment | 24 months after completed treatment | Proportion of patients that don't need adjuvant surgery (arm 1) and number of patients that don't need adjuvant radiotherapy (arm 2) |
| Functional organ preservation | 24 months after completed treatment | Proportion of patients for who an organ-sparing surgery is possible |
| Short term and long term complications | 24 months after completed treatment | According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Treatment related death | 24 months after completed treatment | — |
Countries
Netherlands
Contacts
Primary ContactFrederic Amant, Prof.
Outcome results
None listed