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

Recurrent or Metastatic Head and Neck Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02347332
• Other study ID #: L00070 IN 309 F0
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2014
• Est. completion date: November 23, 2018

Study information

• Verified date: February 2019
• Source: Pierre Fabre Medicament
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 459
• Est. completion date: November 23, 2018
• Est. primary completion date: October 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Recurrent or Metastatic Head and Neck Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Vinflunine

• Methotrexate

Locations

Country	Name	City	State
France	Institut de Recherche Pierre Fabre	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Pierre Fabre Medicament

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Disease Control Rate	Percentage of best overall responses CR, PR and SD in the analysed population	30 months
Secondary	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