A Phase I/II Study Of OSI-774 In Combination With Oxaliplatin, And 5-Fluourouracil In Patients With Metastatic Colorectal Carcinoma
- Determine the maximum tolerated dose of erlotinib when administered with oxaliplatin,
leucovorin calcium, and fluorouracil in patients with metastatic colorectal cancer.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine any antitumor activity of this regimen in these patients.
- Determine the time to progression in patients treated with this regimen.
- Determine the objective response rate and response duration in patients treated with
- Determine the safety and tolerability of this regimen in these patients.
OUTLINE: This is a dose-escalation study of erlotinib.
- Phase I: During the first week of the first course only, patients receive oral
erlotinib daily alone. Patients then begin the regular schedule comprising oral
erlotinib daily, oxaliplatin IV over 2 hours on day 1, and leucovorin calcium IV over 2
hours and fluorouracil IV over 22 hours on days 1 and 2. Treatment repeats every 2
weeks for at least 6 courses in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive erlotinib at the MTD plus oxaliplatin, leucovorin calcium,
and fluorouracil as in phase I. Erlotinib may be administered alone if toxicity is
caused by oxaliplatin, leucovorin calcium, and fluorouracil.
Patients are followed for at least 6 months or until disease progression.
PROJECTED ACCRUAL: A total of 4-18 patients will be accrued for phase I of this study within
1-4 months. A total of 50 patients will be accrued for phase II of this study within 10
Masking: Open Label, Primary Purpose: Treatment
Leonard B. Saltz, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|