RATIONALE: OSI-7904L may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining OSI-7904L with oxaliplatin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of OSI-7904L and oxaliplatin in treating patients with refractory or recurrent advanced colorectal cancer.
OBJECTIVES: Primary * Determine the dose-limiting toxicity of OSI-7904L and oxaliplatin in patients with refractory or recurrent advanced colorectal cancer. * Determine the maximum tolerated dose of this regimen in these patients. * Determine a safe dose for this regimen in these patients. Secondary * Determine the pharmacokinetic profile of this regimen in these patients. * Determine the safety profile of this regimen in these patients. * Determine the antitumor activity of this regimen in these patients. OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study. Patients receive oxaliplatin IV over 2 hours followed by OSI-7904L IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of OSI-7904L and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients receive treatment at the MTD. Patients are followed every 8 weeks. PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Medizinische Hochschule Hannover
Hanover, Germany
Christie Hospital N.H.S. Trust
Manchester, England, United Kingdom
Maximum tolerated dose and recommended dose for future trials as measured by CTC v3.0
Safety profile as measured by CTC v3.0
Response as measured by RECIST every 6 weeks (2 courses)
Pharmacodynamics as measured by drug concentration in the blood during course 1
Time to progression as measured by Kaplan Meier and RECIST every 6 weeks during treatment and then every 8 weeks
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