Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma
obatoclax mesylate
+ topotecan hydrochloride
+ laboratory biomarker analysis
Néoplasmes bronchiques+7
+ Carcinome bronchogénique
+ Néoplasmes pulmonaires
Étude thérapeutique
Résumé
Date de début de l'étude : 1 août 2007
Date à laquelle le premier participant a commencé l'étude.PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose, recommended phase II dose, and toxicity profile of obatoclax mesylate when administered with topotecan hydrochloride in patients with advanced solid tumors. (Phase I) II. Determine the response rate in patients with relapsed or refractory small cell lung cancer treated with obatoclax mesylate and topotecan hydrochloride. (Phase II) SECONDARY OBJECTIVES: I. Evaluate the expression of pro- and anti-apoptotic proteins which may correlate with obatoclax mesylate sensitivity or resistance. OUTLINE: This is a phase I dose-escalation study of obatoclax mesylate followed by a phase II study. PHASE I (solid tumor): Patients receive obatoclax mesylate IV over 3 hours on day 1 OR days 1 and 3 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. PHASE II (small cell lung cancer): Patients receive obatoclax mesylate and topotecan hydrochloride at the recommended phase II dose (RPTD) determined in phase I. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Tumor tissue samples from patients with small cell lung cancer may be collected at baseline for correlative studies. Tissue samples are analyzed for biomarkers and protein expression of Bcl-2, Bcl-Xl, MCL-1, Bax, Bad, c-Myc, L-Myc, and N-Myc by immunohistochemistry. After completion of study treatment, patients are followed for 30 days.
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.22 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
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of 1 of the following: * Advanced solid tumor (phase I) * Topotecan hydrochloride must be an appropriate treatment for this cancer * Small cell lung cancer (SCLC) (phase II) * Progressed after one prior platinum-based chemotherapy regimen * Pathology materials (tumor tissue) will be used for correlative studies, if available * No progressive brain metastases * Treated brain metastases allowed provided patient is neurologically stable and does not require steroids * No leptomeningeal involvement * ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100% * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 100,000/mcL * Total bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Fertile patients must use effective double barrier method of contraception during and for 3 months after completion of study therapy * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered * At least 4 weeks since prior radiotherapy and recovered * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents or anticancer therapy Exclusion Criteria: * History of allergic reactions attributed to compounds of similar chemical or biological composition to obatoclax mesylate or topotecan hydrochloride (e.g., irinotecan) * Concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situations that would limit compliance with study requirements * History of seizure disorder or other neurological dysfunction (except peripheral neuropathy)
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalObjectifs de l'étude
Objectifs principaux
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 2 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, United StatesOuvrir Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital dans Google MapsMemorial Sloan Kettering Cancer Center
New York, United States