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

Phase III Study of IV Vinflunine in Combination With Methotrexate Versus Methotrexate Alone in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-based Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Recurrent or Metastatic Head and Neck Carcinoma
• Intervention / Treatment: Drug: Methotrexate; Drug: Vinflunine

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

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Toulouse, France
    • Institut de Recherche Pierre Fabre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Experimental: Vinflunine plus methotrexate; vinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks	Drug: Vinflunine; Other Names: JAVLOR; VFL
Active Comparator: Methotrexate; methotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks	Drug: Methotrexate; Other Names: MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival in the ITT Population (Months)	Time from randomization to the date of death or last follow-up. The survival duration of patients still alive, was censored at the date of last contact or last follow-up.	Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Time measured from the date of randomisation until date of progression or death from any cause (whichever came first)	an expected average of 4 months
Objective Response Rate (ORR)	The objective response is defined as the best response designation recorded across all time points from the date of randomisation until disease progression.	6 weeks
Disease Control Rate	Percentage of best overall responses CR, PR and SD in the analysed population	30 months
Duration of Response	Duration of objective response will be measured for responders (CR+PR) from the time for CR or PR until the 1st date of documentation of recurrent or progressive disease or the date of death any cause.	30 months

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Investigators: Study Director: Zahida Issiakhem, MD, Institut de Recherche Pierre Fabre

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2014
• Primary Completion (Actual): October 20, 2017
• Study Completion (Actual): November 23, 2018

Study Registration Dates

• First Submitted: November 18, 2014
• First Submitted That Met QC Criteria: January 21, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Vinflunin; Vinflunin + Methotrexate; Metastatic Squamous Cell Carcinoma of the Head and Neck
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: L00070 IN 309 F0

Drug and device information, study documents

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