MK-0646, Etoposide, and Cisplatin in Treating Patients With Extensive-Stage Small Cell Lung Cancer
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.
|Lung Cancer||Biological: anti-IGF-1R recombinant monoclonal antibody MK-0646 Drug: cisplatin Drug: etoposide||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Recommended phase II dose of MK-0646 in combination with standard etoposide and cisplatin chemotherapy [ Time Frame: Each dose level ]Evaluate safety, tolerability in combination with standard chemotherapy.
- Toxicity and tolerability according to NCI CTCAE v3.0 [ Time Frame: Phase 1, each dose level and Phase II ]Look at toxicity and tolerability of MK0646 in combination with standard therapy.
- Preliminary efficacy [ Time Frame: Phase 1 dose levels, evey other cycle ]Look for evidence of response
- Objective response rate [ Time Frame: Phase II portion, every other cycle ]Determine objective response rate including complete response rate, progression free survival and overall survival.
- Predictive and prognostic impact of biomarkers [ Time Frame: Each cycle ]Blood samples will be collected and analyzed for occurrence of human-anti-humanized antibody response to MK0646 as well as IGF-1R analysis.
|Study Start Date:||January 2009|
|Study Completion Date:||July 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
MK-0646, a monoclonial antibody in combination with etoposide and cisplatin.
Biological: anti-IGF-1R recombinant monoclonal antibody MK-0646
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 daysDrug: cisplatin
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 daysDrug: etoposide
MK-0646 should be given 1st followed within 30-60 minutes by cisplatin and then etoposide for cycles which include both MK-0646 and chemotherapy. Cycles are 21 days
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00869752
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|Ottawa Health Research Institute - General Division|
|Ottawa, Ontario, Canada, K1H 8L6|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Peter Ellis, MD||Margaret and Charles Juravinski Cancer Centre|