Obatoclax Mesylate and Topotecan Hydrochloride in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00521144
• Other study ID #: NCI-2009-00252
• Secondary ID: 07-082CDR0000561
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 24, 2007
• Last updated: April 14, 2015
• Start date: August 2007
• Est. completion date: August 2010

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Other known NCT identifiers

• NCT01645657

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Recurrent Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• obatoclax mesylate
Given IV
• topotecan hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (Phase II)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR +PR	Every 6 weeks, assessed up to 30 days	No