Phase III Study of Vinflunine Plus Methotrexate Versus Methotrexate Alone in Patients With Head and Neck Cancer

NCT ID: NCT02347332

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 459 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-25
• Study Completion Date: 2018-11-23

Brief Summary

For patients relapsing after platinum-based therapy, few data are available. The current use of cetuximab associated with radiotherapy in localized disease and associated with platinum-based chemotherapy in the first-line setting stresses the need for new therapeutic options at later stages of SCCHN.Vinca-alkaloids demonstrated activity in SCCHN. Vinflunine demonstrated superior antitumour activity to vinorelbine in preclinical animal models. Recent preliminary phase I results of the vinflunine plus methotrexate combination in SCCHN, based on a clinical review, show encouraging antitumour activity and an acceptable safety profile. Therefore the combination of vinflunine and methotrexate appears a promising salvage regimen after platinum failure.

The present study has been designed as a multicenter, randomised phase III study which will compare the combination of IV vinflunine with methotrexate to methotrexate alone in SCCHN patients having failed platinum-based therapy.

Detailed Description

This study was designed to compare the OS of VFL plus MTX versus MTX alone in patients with SCCHN who had failed platinum-based chemotherapy.

The trial was designed in accordance with current standards used routinely in oncology phase III trials and used established methods of assessment. The RECIST (version 1.1) and NCI CTCAE (version 3.0) guidelines are internationally recognised methods for assessing efficacy and tolerance, respectively.

The patient population was appropriate for this type of phase III study and included adult patients with recurrent and/or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, who had received prior chemotherapy regimens with documented progression. This population of patients was considered appropriate to meet the study objectives.

Recent preliminary phase I results of the VFL plus MTX combination in SCCHN, reported in a clinical review, showed encouraging antitumour activity and an acceptable safety profile A number of chemotherapy agents have been reported as having single-agent activity in SCCHN. However, reliable evidence of efficacy in the second-line setting is lacking, and there is currently no established standard of care. MTX used alone as the reference regimen at a dose of 40 mg/m2/week can be considered as the best available evidence-based option. Also, other trials using this comparator have demonstrated that it is generally accepted as a reasonable choice, and is often used in general practice.

The efficacy and safety assessments employed in this study are standard measures routinely used in studies of this type

Conditions

Recurrent or Metastatic Head and Neck Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vinflunine plus methotrexate

vinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks

Group Type: EXPERIMENTAL

Vinflunine

Intervention Type: DRUG

Methotrexate

methotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Interventions

Vinflunine

Intervention Type: DRUG

Methotrexate

Intervention Type: DRUG

Other Intervention Names

JAVLOR; VFL; MTX

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma
• Documented progressive disease after chemotherapy for locoregionally advanced or recurrent/metastatic SCCHN which included a platinum derivative
• Measurable or non measurable disease
• adequate haematological, hepatic and renal functions
• WHO performance status < 1

Exclusion Criteria

• Nasopharyngeal carcinoma
• History of brain or leptomeningeal involvement
• Albumin level < 35 g/L
• Patients with weight loss ≥ 5% within the last 3 months
• Grade > 2 peripheral neuropathy at study entry
• "Third space" fluids (pleural effusion, ascites, massive edema)
• Prior treatment with vinca-alkaloids and methotrexate

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zahida Issiakhem, MD

Role: STUDY_DIRECTOR

Institut de Recherche Pierre Fabre

Locations

Institut de Recherche Pierre Fabre

Toulouse, , France

Countries

France

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

L00070 IN 309 F0

Identifier Type: -

Identifier Source: org_study_id