Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For LAVC (VULCANIZE-II)

Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For Locally Advanced Vulvar Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of the Vulva; Locally Advanced Vulvar Carcinoma
• Intervention / Treatment: Combination product: Chemoradiation; Drug: Paclitaxel and Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Frederic Amant, Prof.; Phone Number: 0031205129111; Email: f.amant@nki.nl

Study Locations

• Netherlands
  • AMsterdam, Netherlands
    • Recruiting
    • NKI-AvL
    • Contact: F. Amant
  • Leiden, Netherlands
    • Recruiting
    • LUMC
    • Contact: L. Nooij

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Primary chemoradiation; Patients included in the standard treatment arm will receive a combination of weekly cisplatin combined with 30 fractions of external beam radiotherapy on the primary tumour with a total dose of 64.5 Gy. Cisplatin will be given for six weeks intravenously with a dose of 40 mg/m2, if possible on the first day of the week. On day 1 until day 5 the patient will receive external beam radiotherapy. This will be repeated for a six-week period.	Combination product: Chemoradiation; According to standard treatment.
Experimental: NACT (3-weekly carboplatin and paclitaxel) followed by surgery; Patients included in the experimental arm will be treated with intravenous infusion of paclitaxel 175 mg/m2, followed by carboplatin 5 area under the curve (AUC). This will be administered in a 3-weekly scheme with preferably 3 and a maximum of 4 courses, with evaluation after two courses of chemotherapy by physical examination. NACT will be subsequently followed by radical surgery in responding patients. A four to six weeks interval after the last course of chemotherapy needs to be respected before surgery, to allow sufficient physical recovery.	Drug: Paclitaxel and Carboplatin; Paclitaxel 175 mg/m2, followed by carboplatin 5 area under the curve (AUC). This will be administered in a 3-weekly scheme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loco-regional control after 24 months per completed treatment including salvage treatment	Proportion of patients free from local-regional progression	24 months after completed treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-related treatment failure	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.	24 months after completed treatment
Disease free survival		24 months after completed treatment
Patterns of recurrence of disease	Type of recurrence after treatment: local, regional or distant recurrence	24 months after completed treatment
Overall survival		24 months after completed treatment
Treatment related death		24 months after completed treatment
Prevention of trimodal treatment	Proportion of patients that don't need adjuvant surgery (arm 1) and number of patients that don't need adjuvant radiotherapy (arm 2)	24 months after completed treatment
Functional organ preservation	Proportion of patients for who an organ-sparing surgery is possible	24 months after completed treatment
Short term and long term complications	According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	24 months after completed treatment

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Frederic Amant, Prof., NKI-AvL

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Vulvar Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Vulvar Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: M22VL2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No