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
- 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
- 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy
Evaluate safety, tolerability in combination with standard chemotherapy.
Each dose level
Peter Ellis, MD
Margaret and Charles Juravinski Cancer Centre
Canada: Health Canada