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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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
Type d'étude
Inscription (Réel)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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Toulouse, France
- Institut de Recherche Pierre Fabre
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La 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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Vinflunine plus methotrexate
vinflunine IV 280 mg/m² Day 1 plus methotrexate IV 30 mg/m² Day 1 and Day 8 every 3 weeks
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Autres noms:
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Comparateur actif: Methotrexate
methotrexate IV 40 mg/m² Day 1, 8 and 15 every 3 weeks
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Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Overall Survival in the ITT Population (Months)
Délai: Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
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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.
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Participants will be followed till death (if they are not lost for follow-up), an expected average of 7.5 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Progression Free Survival
Délai: an expected average of 4 months
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Time measured from the date of randomisation until date of progression or death from any cause (whichever came first)
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an expected average of 4 months
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Objective Response Rate (ORR)
Délai: 6 weeks
|
The objective response is defined as the best response designation recorded across all time points from the date of randomisation until disease progression.
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6 weeks
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Disease Control Rate
Délai: 30 months
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Percentage of best overall responses CR, PR and SD in the analysed population
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30 months
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Duration of Response
Délai: 30 months
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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.
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30 months
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Zahida Issiakhem, MD, Institut de Recherche Pierre Fabre
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Tumeurs par site
- Tumeurs, glandulaires et épithéliales
- Tumeurs de la tête et du cou
- Carcinome épidermoïde
- Carcinome
- Carcinome épidermoïde de la tête et du cou
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Agents antirhumatismaux
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents dermatologiques
- Agents de contrôle de la reproduction
- Agents abortifs, non stéroïdiens
- Agents abortifs
- Antagonistes de l'acide folique
- Méthotrexate
Autres numéros d'identification d'étude
- L00070 IN 309 F0
Informations sur les médicaments et les dispositifs, documents d'étude
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