Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For LAVC

Squamous Cell Carcinoma of the Vulva Clinical Trial

— VULCANIZE-II  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05905315
• Other study ID #: M22VL2
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: September 1, 2029

Study information

• Verified date: April 2024
• Source: The Netherlands Cancer Institute
• Contact: Frederic Amant, Prof.
• Phone: 0031205129111
• Email: f.amant[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: September 1, 2029
• Est. primary completion date: September 1, 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Squamous Cell Carcinoma of the Vulva
• Vulvar Neoplasms

Intervention

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.

Combination Product:
• Chemoradiation
According to standard treatment.

Locations

Country	Name	City	State
Netherlands	NKI-AVL	AMsterdam
Netherlands	LUMC	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Disease free survival		24 months after completed treatment
Secondary	Patterns of recurrence of disease	Type of recurrence after treatment: local, regional or distant recurrence	24 months after completed treatment
Secondary	Overall survival		24 months after completed treatment
Secondary	Treatment related death		24 months after completed treatment
Secondary	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
Secondary	Functional organ preservation	Proportion of patients for who an organ-sparing surgery is possible	24 months after completed treatment
Secondary	Short term and long term complications	According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	24 months after completed treatment