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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Recurrent Small Cell Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum-tolerated dose of obatoclax mesylate when administered with topotecan hydrochloride (phase I)

Outcome Time Frame:

From the time of first treatment to up to 30 days

Safety Issue:

No

Principal Investigator

Lee Krug

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00252

NCT ID:

NCT00521144

Start Date:

August 2007

Completion Date:

Related Keywords:

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

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins HospitalBaltimore, Maryland  21231