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

Primary Purpose

Locally Advanced Vulvar Carcinoma, Squamous Cell Carcinoma of the Vulva

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Paclitaxel and Carboplatin
Chemoradiation
Sponsored by
The Netherlands Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Vulvar Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Woman ≥ 18 years Signed and written informed consent. Histologically-confirmed primary or recurrent squamous cell carcinoma vulvar cancer FIGO stage II - IVa, T2 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; T2 or larger tumour with (irresectable) groin metastases T2 or larger tumour with 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 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Primary chemoradiation

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

    Arm 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.

    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.

    Outcomes

    Primary Outcome Measures

    Loco-regional control after 24 months per completed treatment including salvage treatment
    Proportion of patients free from local-regional progression

    Secondary Outcome Measures

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

    Full Information

    First Posted
    December 12, 2022
    Last Updated
    June 6, 2023
    Sponsor
    The Netherlands Cancer Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05905315
    Brief Title
    Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For LAVC
    Acronym
    VULCANIZE-II
    Official Title
    Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For Locally Advanced Vulvar Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    September 1, 2029 (Anticipated)
    Study Completion Date
    September 1, 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    The Netherlands Cancer Institute

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Locally Advanced Vulvar Carcinoma, Squamous Cell Carcinoma of the Vulva

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    98 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Primary chemoradiation
    Arm Type
    Active Comparator
    Arm 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.
    Arm Title
    NACT (3-weekly carboplatin and paclitaxel) followed by surgery
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Paclitaxel and Carboplatin
    Intervention Description
    Paclitaxel 175 mg/m2, followed by carboplatin 5 area under the curve (AUC). This will be administered in a 3-weekly scheme.
    Intervention Type
    Combination Product
    Intervention Name(s)
    Chemoradiation
    Intervention Description
    According to standard treatment.
    Primary Outcome Measure Information:
    Title
    Loco-regional control after 24 months per completed treatment including salvage treatment
    Description
    Proportion of patients free from local-regional progression
    Time Frame
    24 months after completed treatment
    Secondary Outcome Measure Information:
    Title
    Disease-related treatment failure
    Description
    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.
    Time Frame
    24 months after completed treatment
    Title
    Disease free survival
    Time Frame
    24 months after completed treatment
    Title
    Patterns of recurrence of disease
    Description
    Type of recurrence after treatment: local, regional or distant recurrence
    Time Frame
    24 months after completed treatment
    Title
    Overall survival
    Time Frame
    24 months after completed treatment
    Title
    Treatment related death
    Time Frame
    24 months after completed treatment
    Title
    Prevention of trimodal treatment
    Description
    Proportion of patients that don't need adjuvant surgery (arm 1) and number of patients that don't need adjuvant radiotherapy (arm 2)
    Time Frame
    24 months after completed treatment
    Title
    Functional organ preservation
    Description
    Proportion of patients for who an organ-sparing surgery is possible
    Time Frame
    24 months after completed treatment
    Title
    Short term and long term complications
    Description
    According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
    Time Frame
    24 months after completed treatment

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Gender Eligibility Description
    Vulva carcinoma
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Woman ≥ 18 years Signed and written informed consent. Histologically-confirmed primary or recurrent squamous cell carcinoma vulvar cancer FIGO stage II - IVa, T2 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; T2 or larger tumour with (irresectable) groin metastases T2 or larger tumour with 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 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Frederic Amant, Prof.
    Phone
    0031205129111
    Email
    f.amant@nki.nl
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Frederic Amant, Prof.
    Organizational Affiliation
    NKI-AvL
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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