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

Netherlands Cancer Institute (NKI)

Status and phase: Enrolling; Phase 2

Conditions: Squamous Cell Carcinoma of the Vulva; Locally Advanced Vulvar Carcinoma

Treatments: Drug: Paclitaxel and Carboplatin; Combination Product: Chemoradiation

Study type: Interventional

Funder types: Other

Identifiers

NCT05905315

M22VL2

Details and patient eligibility

About

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.

Enrollment: 98 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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98 participants in 2 patient groups

Primary chemoradiation

Active Comparator group

Description:

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.

Treatment:

Combination Product: Chemoradiation

NACT (3-weekly carboplatin and paclitaxel) followed by surgery

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel and Carboplatin