A Phase I-II Trial of MK-0646, a Monoclonal Antibody Against Insulin-Like Growth Factor-1 Receptor, in Combination With Etoposide and Cisplatin in 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.