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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
obatoclax mesylate
topotecan hydrochloride
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy and chemotherapy)

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
August 24, 2007
Last Updated
April 14, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00521144
Brief Title
Obatoclax Mesylate and Topotecan Hydrochloride in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors
Official Title
Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Small Cell Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy and chemotherapy)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
obatoclax mesylate
Other Intervention Name(s)
GX15-070MS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Other Intervention Name(s)
hycamptamine, Hycamtin, SKF S-104864-A, TOPO
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall Response Rate (Phase II)
Description
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
Time Frame
Every 6 weeks, assessed up to 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee Krug
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21620511
Citation
Paik PK, Rudin CM, Pietanza MC, Brown A, Rizvi NA, Takebe N, Travis W, James L, Ginsberg MS, Juergens R, Markus S, Tyson L, Subzwari S, Kris MG, Krug LM. A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer. Lung Cancer. 2011 Dec;74(3):481-5. doi: 10.1016/j.lungcan.2011.05.005. Epub 2011 May 26.
Results Reference
derived

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

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