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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00521144
First received: August 24, 2007
Last updated: July 21, 2014
Last verified: December 2013

August 24, 2007
July 21, 2014
August 2007
August 2010   (final data collection date for primary outcome measure)
Overall Response Rate (Phase II) [ Time Frame: Every 6 weeks, assessed up to 30 days ] [ Designated as safety issue: No ]
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
  • Toxicity profile of obatoclax mesylate and topotecan hydrochloride (phase I)
  • Maximum tolerated dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I)
  • Recommended phase II dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I)
  • Overall response rate (phase II)
Complete list of historical versions of study NCT00521144 on ClinicalTrials.gov Archive Site
Not Provided
Expression of pro- and anti-apoptotic proteins
Not Provided
Not Provided
 
Obatoclax Mesylate and Topotecan Hydrochloride in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer or Advanced Solid Tumors
Phase I/II Study of Obatoclax Mesylate (GX15-070MS), a Bcl-2 Antagonist, Plus Topotecan in Relapsed Small Cell Lung Carcinoma

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

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Small Cell Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
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
Interventions:
  • Drug: obatoclax mesylate
  • Drug: topotecan hydrochloride
  • Other: laboratory biomarker analysis
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
August 2010
August 2010   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00521144
NCI-2009-00252, 07-082, CDR0000561779
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Lee Krug Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP