RATIONALE: Monoclonal antibodies, such as MK-0646, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of MK-0646 when given together with etoposide and cisplatin and to see how well it works in treating patients with extensive-stage small cell lung cancer.

OBJECTIVES:

• To determine the recommended phase II dose of MK-0646 in combination with a standard etoposide and cisplatin chemotherapy regimen in patients with extensive stage small cell lung cancer. (phase I)
• To assess the toxicity and tolerability of this regimen in these patients. (phases I and II)
• To evaluate the preliminary efficacy of this regimen in these patients. (phase I)
• To assess the efficacy of this regimen, in terms of objective response rate, as well as complete response rate in these patients. (phase II)
• To assess progression-free survival and overall survival of patients treated with this regimen. (phase II)
• To explore the predictive and prognostic impact of biomarkers in patients treated with this regimen. (phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of MK-0646 followed by a phase II study.

Patients receive MK-0646 IV over 1 hour on days 1, 8, and 15 and cisplatin IV and etoposide IV once daily on days 1-3. Treatment repeats every 3 weeks for 4 to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients with complete response (CR) or partial response (PR) may continue MK-0646 in the absence of disease progression, with temporary discontinuation while undergoing prophylactic cranial irradiation or thoracic radiotherapy.

Blood samples are collected at baseline (pre-dose) and periodically for biomarker and pharmacogenetic correlative studies. Blood samples are analyzed for changes in expression of IGF biomarkers (e.g., IGF-1, IGF-2 and IGF-PB), haplotype tagging analysis of the IGF-1R, and evaluation of the immunoglobulin G fragment C receptor polymorphisms.

After completion of study therapy, patients are followed at 4 weeks. Patients with responding disease (i.e., CR, PR, or stable disease) are followed every 3 months until relapse or progression.

DISEASE CHARACTERISTICS:

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

  • Extensive stage disease that is incurable but amenable to treatment with platinum-based chemotherapy
  • Small cell and variant histologies allowed
  • No mixed tumors (i.e., small and large cell) or other neuroendocrine tumors of the lung

• Clinically and/or radiologically documented measurable disease, defined as ≥ 1 unidimensionally measurable site of disease ≥ 20 mm by chest x-ray, ≥ 15 mm by CT scan (lymph nodes), or ≥ 10 mm by CT scan or physical exam

• No uncontrolled or symptomatic CNS metastases

  • Patients who have completed radiotherapy or have undergone complete resection of CNS metastases are allowed provided they are on stable (non-increasing) or decreasing doses of corticosteroids

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks

• ECOG performance status 0-2

• Absolute granulocyte count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Total bilirubin ≤ upper limit of normal (ULN)

• AST and ALT ≤ 3 times ULN (≤ 5 times ULN if documented liver metastases)

• Serum creatinine ≤ ULN OR creatinine clearance ≥ 50 mL/min

• Not pregnant or lactating

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy

• No other active cancer

• No untreated and/or uncontrolled cardiovascular or other comorbid conditions

  • Patients with a significant cardiac history, even if controlled, should have a LVEF > 50%

• No uncontrolled diabetes

• Must be accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior cytotoxic chemotherapy or other IGF-1R targeting agents for SCLC

• At least 3 weeks since prior radiotherapy to neurological sites

• No prior radiotherapy to the lungs

• Prior surgery allowed provided that wound healing has occurred

  • At least 14 days since prior major surgery

• No other concurrent investigational agents or therapy

• No other concurrent anticancer treatment

• No concurrent radiotherapy