Obatoclax Mesylate and Topotecan Hydrochloride in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors
This phase I/II trial is studying the side effects and best dose of obatoclax mesylate when given together with topotecan hydrochloride and to see how well they work in treating patients with relapsed or refractory small cell lung cancer or advanced solid tumors. Obatoclax mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with topotecan hydrochloride may help kill more tumor cells
Recurrent Small Cell Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: obatoclax mesylate
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma|
- Maximum-tolerated dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I) [ Time Frame: From the time of first treatment to up to 30 days ] [ Designated as safety issue: No ]
- Recommended phase II dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I) [ Time Frame: Assessed up to 30 days ] [ Designated as safety issue: Yes ]The recommended phase II dose will be the highest dose level at which only 0 or 1 out of 6 patients experienced a dose-limiting toxicity (DLT). DLT is defined as an adverse event (AE) that due to its type, severity, or relationship to study drug must be counted towards determining the maximally administered dose. For purposes of this study with obatoclax mesylate and topotecan, the AEs outlined below will be considered DLTs.
- Toxicity profile of obatoclax mesylate and topotecan hydrochloride (phase I) [ Time Frame: From time to first treatment, assessed up to 30 days ] [ Designated as safety issue: Yes ]Toxicity will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
- Overall response rate (phase II) [ Time Frame: Every 6 weeks, assessed up to 30 days ] [ Designated as safety issue: No ]Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
- Expression of pro- and anti-apoptotic proteins [ Time Frame: At baseline ] [ Designated as safety issue: No ]This data will then be compared to the degree of response to obatoclax mesylate and topotecan hydrochloride.
|Study Start Date:||August 2007|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy and chemotherapy)
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
Drug: obatoclax mesylate
Other Name: GX15-070MSDrug: topotecan hydrochloride
Other Names:Other: laboratory biomarker analysis
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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521144
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Lee Krug||Memorial Sloan-Kettering Cancer Center|