Clinical trial NCT02347332: Phase III Study of Vinflunine Plus Methotrexate Versus Methotrexate Alone in Patients With Head and Neck Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Recurrent or Metastatic Head and Neck Carcinoma
Keywords: Vinflunin
Vinflunin + Methotrexate
Metastatic Squamous Cell Carcinoma of the Head and Neck
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2015-01-27
Enrollment: 459
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Overall Survival in the ITT Population (Months)
timeFrame: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: an expected average of 4 months
measure: Objective Response Rate (ORR)
timeFrame: 6 weeks
measure: Disease Control Rate
timeFrame: 30 months
measure: Duration of Response
timeFrame: 30 months
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Institut de Recherche Pierre Fabre
Study officials:
affiliation: Institut de Recherche Pierre Fabre
name: Zahida Issiakhem, MD
role: STUDY_DIRECTOR
References: