Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma
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)
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I)
From the time of first treatment to up to 30 days
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Baltimore, Maryland 21231|