Clinical trial NCT00248482: Imatinib Mesylate After Irinotecan and Cisplatin in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Official title: Phase II Trial of Imatinib Mesylate Maintenance Therapy in Patients With C-Kit (+) Extensive-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
recurrent small cell lung cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Novartis Pharmaceuticals
First posted: 2005-11-04
Enrollment: 6
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: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving imatinib mesylate after irinotecan and cisplatin may keep the tumor from coming back.

PURPOSE: This phase II trial is studying how well giving imatinib mesylate after irinotecan and cisplatin works in treating patients with extensive-stage small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the 4-month progression-free survival rate in patients with c-kit positive, extensive stage small cell lung cancer treated with maintenance therapy comprising imatinib mesylate after induction therapy comprising irinotecan and cisplatin.

Secondary

* Determine the overall survival of patients treated with this regimen.
* Determine the tolerability of imatinib mesylate maintenance therapy in these patients.
* Determine the response rate in patients treated with irinotecan and cisplatin.

OUTLINE: This is a multicenter study.

* Induction therapy: Patients receive irinotecan IV over 90 minutes on days 1 and 8 and cisplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response (partial or complete) or stable disease proceed to maintenance therapy.
* Maintenance therapy: Patients receive oral imatinib mesylate twice daily for 6 months in the absence of disease progression or unacceptable toxicity. Some patients may continue to receive therapy for up to 1 year.

After completion of study treatment, patients are followed for 4 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed small cell lung cancer (SCLC)

  * Extensive stage disease, defined by 1 of the following criteria:

    * Disease extends beyond one hemithorax and regional lymph nodes
    * Cytologically positive pleural effusion
* Meets 1 of the following criteria:

  * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion outside the field of any prior radiotherapy
  * Evaluable disease
* No history of untreated or symptomatic brain or leptomeningeal metastases

  * Prior brain metastases allowed provided patient is neurologically stable for 2 weeks after completion of therapy

PATIENT CHARACTERISTICS:

Performance status

* SWOG 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 8 g/dL

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Meets 1 of the following criteria:

  * Alkaline phosphatase (AP) normal AND AST and ALT ≤ 2.5 times ULN
  * AP ≤ 5 times ULN AND AST and ALT normal
* No acute or chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

Renal

* Creatinine normal OR
* Creatinine clearance ≥ 65 mL/min

Cardiovascular

* No uncontrolled congestive heart failure
* No uncontrolled angina
* No myocardial infarction and/or stroke within the past 3 months

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after completion of study treatment
* No peripheral neuropathy ≥ grade 2
* No symptomatic edema from any etiology
* No known HIV positivity
* No other serious medical illness
* No other malignancy within the past 3 years except adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
* No history of dementia, active psychiatric disorder, or other condition that would preclude study compliance or ability to take oral medication on a daily basis

PRIOR CONCURRENT THERAPY:

Chemotherapy

* No prior chemotherapy for SCLC

Endocrine therapy

* No concurrent routine systemic corticosteroids

Radiotherapy

* See Disease Characteristics
* At least 2 weeks since prior palliative radiotherapy

Surgery

* More than 2 weeks since prior major surgery

Other

* No concurrent therapeutic anticoagulation with warfarin

  * Concurrent low molecular weight heparin allowed provided regimen was initiated ≥ 2 weeks prior to study entry
* No other concurrent participation in another study of an investigational agent

Primary outcomes:
measure: Progression-free survival
timeFrame: at 4 months
Secondary outcomes:
measure: Overall survival
timeFrame: at least 4 months after discontinuation of treatment
measure: Tolerability of Gleevec maintenance therapy
timeFrame: 30 days after completion of study treatment
measure: Response rate as measured by RECIST at
timeFrame: Baseline and every 8 weeks during study treatment
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Shirish M. Gadgeel, MD
role: PRINCIPAL_INVESTIGATOR
References: