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Obatoclax Mesylate and Topotecan in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
First Received: August 24, 2007   Last Updated: April 30, 2009   History of Changes
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00521144
  Purpose

RATIONALE: 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, 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 may help kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of obatoclax mesylate when given together with topotecan and to see how well they work in treating patients with relapsed or refractory small cell lung cancer or advanced solid tumors.


Condition Intervention Phase
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
 Drug: obatoclax mesylate
Drug: topotecan hydrochloride
 Phase I
Phase II

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Topotecan hydrochloride Topotecan Obatoclax mesylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I) [ Designated as safety issue: No ]
  • Recommended phase II dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I) [ Designated as safety issue: Yes ]
  • Toxicity profile of obatoclax mesylate and topotecan hydrochloride (phase I) [ Designated as safety issue: Yes ]
  • Overall response rate (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Expression of pro- and anti-apoptotic proteins [ Designated as safety issue: No ]

Estimated Enrollment: 59
Study Start Date: August 2007
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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)
  • Determine the response rate in patients with relapsed or refractory small cell lung cancer treated with obatoclax mesylate and topotecan hydrochloride. (Phase II)

Secondary

  • Evaluate the expression of pro- and anti-apoptotic proteins which may correlate with obatoclax mesylate sensitivity or resistance.

OUTLINE: This is a multicenter 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 are 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 6 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for the phase I portion of the study. A total of 29 patients will be accrued for the phase II portion of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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
      • Adequate pathology materials (tumor tissue) must be available for correlative studies

  • No progressive brain metastases

    • Treated brain metastases allowed provided patient is neurologically stable and does not require steroids
  • No leptomeningeal involvement

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • 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
  • QTc ≤ 450 msec
  • Not pregnant or nursing
  • Fertile patients must use effective double barrier method of contraception during and for 3 months after completion of study 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)

PRIOR CONCURRENT 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521144

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lee M. Krug, MD     212-639-8420        
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lee M. Krug, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Naiyer Rizvi, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center ( Lee M. Krug )
Study ID Numbers: CDR0000561779, MSKCC-07082
Study First Received: August 24, 2007
Last Updated: April 30, 2009
ClinicalTrials.gov Identifier: NCT00521144     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent small cell lung cancer
unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Recurrence
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
Neuroectodermal Tumors
Respiratory Tract Diseases
 Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Topotecan
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Carcinoma, Neuroendocrine
Antineoplastic Agents
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Pharmacologic Actions
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
 Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Topotecan
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009



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