This partially randomized phase I/II trial studies the side effects and best dose of sunitinib malate and to see how well it works when given together with cisplatin or carboplatin and etoposide in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cisplatin or carboplatin and etoposide are more effective when given with or without sunitinib malate in treating small cell lung cancer.
PRIMARY OBJECTIVES: I. To determine the phase II dose for sunitinib (sunitinib malate) combined with cisplatin and etoposide. (Phase IB) II. To compare the progression-free survival of patients with extensive stage small cell lung cancer treated with cisplatin or carboplatin and etoposide followed by maintenance sunitinib to patients receiving the same chemotherapy followed by placebo. (Phase II) SECONDARY OBJECTIVES: I. To assess the single agent response rate for sunitinib given as monotherapy after chemotherapy. (Phase II) II. To assess the overall survival of patients treated with cisplatin or carboplatin and etoposide followed by sunitinib. (Phase II) III. To evaluate the toxicity and tolerability of maintenance sunitinib after cisplatin or carboplatin and etoposide. (Phase II) IV. To determine the association between vascular endothelial growth factor (VEGF) plasma levels and tumor response. (Phase II) OUTLINE: This is a phase I, dose-escalation study of sunitinib malate followed by a randomized phase II study. PHASE I (close to accrual 5/17/08): COMBINATION THERAPY: Patients receive cisplatin or carboplatin intravenously (IV) on day 1, etoposide IV on days 1-3, and sunitinib malate orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive sunitinib malate PO alone QD. Treatment continues in the absence of disease progression or unacceptable toxicity. PHASE II: COMBINATION THERAPY: Patients receive cisplatin or carboplatin and etoposide as in Phase I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 3-8 weeks after completion of combination chemotherapy or \>= 4 courses of combination therapy, patients with a responding or stable disease are randomized to 1 of 2 treatment arms. All patients must be euthyroid before starting on maintenance therapy. ARM I: Patients receive sunitinib malate PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
156
Given IV
Given IV
Given IV
Correlative studies
Given PO
Given PO
Arroyo Grande Community
Arroyo Grande, California, United States
PCR Oncology
Arroyo Grande, California, United States
East Bay Radiation Oncology Center
Castro Valley, California, United States
Valley Medical Oncology Consultants-Castro Valley
Castro Valley, California, United States
Bay Area Breast Surgeons Inc
Emeryville, California, United States
Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)
The maximum tolerated dose is defined at the highest sunitinib dose at which less than one third of participants develop a dose limiting toxicity (DLT). A DLT is defined as: delay of beginning cycle 2 of chemotherapy by \> 7 days due to neutropenia, grade 4 hematologic toxicity lasting greater than 1 week (chemotherapy alone would be expected to cause significant grade 4 hematologic toxicity) or grade 3 or 4 nonhematologic toxicity (excluding grade 3 or 4 fatigue if the patient is found to be hypothyroid and responds to fatigue \< grade 3 with thyroid replacement therapy).
Time frame: 21 days
Progression-free Survival (Phase II)
Progression free survival (PFS) was defined as the time from maintenance randomization to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time frame: Up to 3 years
Overall Survival
Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time frame: Up to 3 years
Number of Participants With Overall Tumor Response
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.
Time frame: Up to 3 years
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