Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
Collecte de données
Gliome+9
+ Néoplasmes germinaux et embryonnaires
+ Néoplasmes par type histologique
Étude thérapeutique
Résumé
Date de début de l'étude : 1 mars 2004
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: Primary * Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when administered with temozolomide in patients with recurrent primary supratentorial gliomas. * Determine the safety and tolerability of this regimen in these patients. Secondary * Determine the mechanism of action of lonafarnib in these patients. * Determine the pharmacodynamics and pharmacokinetics of this regimen in these patients. * Determine the activity of this regimen in these patients. * Determine the response to this regimen in patients who have measurable disease. OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study of lonafarnib. Patients receive oral temozolomide once daily on days 2-6 of course 1 and on days 1-5 of all subsequent courses. Patients also receive oral lonafarnib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experience dose-limiting toxicity. An additional 3 patients may be treated at the highest dose level achieved. Patients are followed every 8 weeks for 6 months and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.30 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
DISEASE CHARACTERISTICS: * Histologically confirmed primary supratentorial glioma * Multifocal disease allowed * Recurrent disease after prior surgery and/or radiotherapy * Radiological evidence of increased and/or enhanced target lesion * Amenable to temozolomide therapy PATIENT CHARACTERISTICS: Age * Over 18 Performance status * ECOG 0-2 OR * WHO 0-2 Life expectancy * Not specified Hematopoietic * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL Hepatic * Alkaline phosphatase \< 2.5 times upper limit of normal (ULN) * Transaminases \< 2.5 times ULN * Bilirubin \< 1.5 times ULN Renal * Creatinine \< 1.7 mg/dL Cardiovascular * Cardiac function clinically normal * Normal 12-lead ECG * QTc ≤ 440 msec on ECG * No ischemic heart disease within the past 6 months Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No unstable systemic disease * No active uncontrolled infection * No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up * No other active or recurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent anticancer biologic agents Chemotherapy * At least 4 weeks since prior chemotherapy (6 weeks for temozolomide) * Prior adjuvant chemotherapy allowed * No more than 1 prior chemotherapy regimen for recurrent disease * No other concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids allowed provided treatment remains at a stable or decreasing dose for at least 2 weeks Radiotherapy * See Disease Characteristics * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 3 months since prior surgery for primary brain tumor Other * Concurrent anticonvulsants allowed * No other concurrent anticancer agents * No other concurrent investigational therapy
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Objectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 3 sites
Centre Regional Rene Gauducheau
Nantes-Saint Herblain, FranceCentre Hospitalier Universitaire Vaudois
Lausanne, Switzerland