A Study of ZD1839 (Iressa) in Combination With Oxaliplatin, 5-Fluorouracil (5-FU) and Leucovorin (LV) in Advanced Solid Malignancies (Phase I) and Advanced Colorectal Cancers (Phase II)
- Determine the maximum tolerated dose of gefitinib and oxaliplatin when combined with
fluorouracil and leucovorin calcium in patients with advanced solid tumors. (Phase I)
(Phase I closed as of 5/30/02)
- Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.
- Determine the dose-limiting toxic effects and other toxic effects of this regimen in
- Determine the antitumor response in patients with advanced colorectal adenocarcinoma
treated with this regimen. (Phase II)
- Determine the overall survival and time to progression in patients with advanced
colorectal adenocarcinoma treated with this regimen. (Phase II)
- Determine the presence of polymorphisms or other genetic alterations in genes
implicated in the action of this regimen and determine their possible relationship with
toxic effects of and antitumor response to this regimen in these patients.
OUTLINE: This is a dose-escalation study of gefitinib and oxaliplatin (L-OHP).
- Phase I (closed as of 5/30/02): Patients receive L-OHP IV over 2 hours on day 1 and
leucovorin calcium (CF) IV over 2 hours followed by fluorouracil (5-FU) IV bolus and
5-FU IV over 22 hours on days 1 and 2 during all courses. Beginning with course 2,
patients also receive oral gefitinib daily on days 1-14. Courses repeat every 2 weeks
in the absence of disease progression or unacceptable toxicity. Patients who achieve
complete response (CR) receive 2 additional courses past CR.
Sequential dose escalation of gefitinib is followed by sequential dose escalation of L-OHP.
Cohorts of 3-6 patients receive escalating doses of gefitinib and L-OHP until the maximum
tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients are stratified according to prior therapy:
- Stratum A: Received no prior therapy or received adjuvant 5-FU/CF or adjuvant
5-FU/CF/irinotecan at least 6 months ago
- Stratum B: Received prior therapy for metastatic disease or received adjuvant
5-FU/CF fewer than 6 months ago or prior irinotecan Patients receive therapy as in
phase I (closed as of 5/30/02) with L-OHP and gefitinib at the recommended phase
PROJECTED ACCRUAL: Approximately 12-15 patients will be accrued for phase I of the study
within 4-6 months (Phase I closed as of 5/30/02). A total of 30-81 patients (18-46 for
stratum A and 12-35 for stratum B) will be accrued for phase II of the study within 18
Primary Purpose: Treatment
Branimir I. Sikic, MD
United States: Federal Government
|Stanford Cancer Center at Stanford University Medical Center||Stanford, California 94305|