Combination Chemotherapy and Imatinib Mesylate in Treating Patients With Extensive-Stage Small Cell Lung Cancer - Full Text View

Sponsor:	Princess Margaret Hospital, Canada
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00052494

Purpose

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

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

Condition	Intervention	Phase
Lung Cancer	Drug: cisplatin Drug: imatinib mesylate Drug: irinotecan hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	A Phase I Study Of STI 571 (Gleevec) In Combination With Cisplatin/Irinotecan In Patients With Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Irinotecan U 101440E Irinotecan hydrochloride Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	April 2003
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of imatinib mesylate when administered with cisplatin and irinotecan in patients with extensive stage small cell lung cancer.
Determine the recommended phase II dose of imatinib mesylate in patients treated with this regimen.
Determine the response rate, median duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen.

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

Patients receive cisplatin IV over 1 hour on day 1 and irinotecan IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for a maximum of 4 courses. Patients also receive oral imatinib mesylate daily continually for one week prior to, during, and after chemotherapy in the absence of 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 at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose (one dose level below the MTD).

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 1-2 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed extensive stage small cell lung cancer
- Incurable but amenable to treatment with chemotherapy
- c-kit positive by immunohistochemistry of original biopsy or other metastatic site
At least one unidimensionally measurable lesion
- > 20 mm by conventional techniques or > 10 mm by spiral CT scan
- No prior radiotherapy to target measurable lesion(s), unless there is documented disease progression
No known brain metastases

PATIENT CHARACTERISTICS:

Age

Not specified

Performance status

ECOG 0-1 OR
Karnofsky 70-100%

Life expectancy

More than 6 weeks

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal
AST and/or ALT ≤ 2.5 times upper limit of normal

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

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

Gastrointestinal

No concurrent untreated upper gastrointestinal bleeding that has not been fully investigated
No gastrointestinal disease that would impair drug absorption

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception prior to, during, and for 3 months after study participation
No history of ototoxicity
No history of peripheral neuropathy
No traumatic injury within the past 21 days
No ongoing or active infection
No other concurrent significant medical condition that would preclude study participation
No concurrent psychiatric condition or social situation that would preclude study compliance
No other malignancy within the past 5 years except treated nonmelanoma skin cancer, carcinoma in situ, or stage A prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

See Disease Characteristics
No prior chemotherapy
No other concurrent chemotherapy

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy
No prior radiotherapy to more than 25% of marrow

Surgery

More than 3 weeks since prior major surgery
No prior surgical procedure impairing absorption

Other

No prior c-kit-targeted therapy
No concurrent therapeutic dose of warfarin
- Mini-dose warfarin for prophylaxis and low-molecular weight heparin allowed
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No concurrent amifostine
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052494

Locations

Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Princess Margaret Hospital, Canada

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark D. Vincent, MD

London Regional Cancer Program at London Health Sciences Centre

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00052494 History of Changes
Other Study ID Numbers:	CDR0000258487, PMH-PHL-008, NCI-5684
Study First Received:	January 24, 2003
Last Updated:	February 19, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

extensive stage small cell lung cancer
recurrent small cell lung cancer

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
Irinotecan
Imatinib
Cisplatin

Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012