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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00521144
First received: August 24, 2007
Last updated: November 21, 2012
Last verified: August 2012
  Purpose

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


Condition Intervention Phase
Recurrent Small Cell Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: obatoclax mesylate
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


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) [ 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 59
Study Start Date: August 2007
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given IV
Other Name: GX15-070MS
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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 Hospital
Baltimore, Maryland, United States, 21231
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Lee Krug Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00521144     History of Changes
Obsolete Identifiers: NCT01645657
Other Study ID Numbers: NCI-2009-00252, 07-082, CDR0000561779
Study First Received: August 24, 2007
Last Updated: November 21, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014