Clinical trial NCT00521144: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Small Cell Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Overall Response Rate (Phase II)
timeFrame: Every 6 weeks, assessed up to 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lee Krug
role: PRINCIPAL_INVESTIGATOR
References:
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.