Imatinib Mesylate and Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 1

Conditions

Lung Cancer

Treatments

Drug: cisplatin

Drug: irinotecan hydrochloride

Drug: imatinib mesylate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00045604

CDR0000256923

MSKCC-02015

NCI-5653

Details and patient eligibility

About

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining imatinib mesylate with irinotecan and cisplatin in treating patients who have extensive-stage small cell lung cancer

Full description

OBJECTIVES:

Determine the maximum tolerated dose of imatinib mesylate when administered with irinotecan and cisplatin in patients with extensive stage small cell lung cancer.
Determine the effect of imatinib mesylate on irinotecan metabolism by the cytochrome p450 system in these patients.
Determine the response rate, time to progression, and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive irinotecan IV over 30 minutes on days 1, 8, and 15 and cisplatin IV over 60 minutes on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral imatinib mesylate once or twice daily beginning on day 22 of course 1 and continuing until disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study within 12-18 months.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed small cell lung cancer
- Extensive stage disease
Measurable or evaluable indicator lesion
No symptomatic or uncontrolled brain or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

WBC at least 4,000/mm3
Platelet count at least 160,000/mm3
Hemoglobin at least 10 g/dL

Hepatic

Bilirubin no greater than 1 mg/dL
AST no greater than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 5 times ULN

Renal

Creatinine less than 1.5 mg/dL OR
Creatinine clearance at least 50 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No uncontrolled cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after study
No other active cancer except previously treated carcinoma in situ, non -melanoma skin cancer, or stage I prostate cancer
No ongoing or active infection
No psychiatric illness or social situation that would preclude study
No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy