A Phase I/ Randomized Phase II Trial Of Oxaliplatin (NSC #266046) With Or Without ZD 1839 (NSC # 715055) In Patients With Advanced Colorectal Carcinoma
- Determine the recommended phase II dose of gefitinib when administered in combination
with oxaliplatin in patients with metastatic or locally recurrent colorectal cancer.
- Determine the dose-limiting toxicity of this regimen in these patients.
- Compare the time to progression, objective response rate, and median and overall
survival in patients treated with oxaliplatin with or without gefitinib.
- Compare the toxicity of these regimens in these patients.
OUTLINE: This is a phase I dose-escalation study of gefitinib followed by a phase II
randomized, multicenter study. Patients are stratified according to ECOG performance status
(0 vs 1-2).
- Phase I: Patients receive oxaliplatin IV over 2 hours on day 1 and oral gefitinib once
daily on days 1-21. Treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Phase II: Patients are randomized to one of two treatment arms.
- Arm I: Patients receive oxaliplatin IV over 2 hours on day 1.
- Arm II: Patients receive oxaliplatin as in arm I and oral gefitinib once daily at
the MTD on days 1-21.
In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients in arm II with stable or responding disease
after 6 courses may continue to receive gefitinib alone until disease progression.
PROJECTED ACCRUAL: Approximately 77 patients (9 for phase I and 68 for phase II) will be
accrued for this study within 12-14 months.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended dose of ZD1839 in combination with oxaliplatin
Hedy L. Kindler, MD
University of Chicago
United States: Federal Government
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|Loyola University Medical Center||Maywood, Illinois 60153|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Memorial Hospital of South Bend||South Bend, Indiana 46601|
|Evanston Northwestern Health Care||Evanston, Illinois 60201|
|Louis A. Weiss Memorial Hospital||Chicago, Illinois 60640|
|Oncology/Hematology Associates of Central Illinois, P.C.||Peoria, Illinois 61602|
|Central Illinois Hematology Oncology Center||Springfield, Illinois 62701|
|Fort Wayne Medical Oncology and Hematology, Inc.||Fort Wayne, Indiana 46885-5099|
|Decatur Memorial Hospital Cancer Care Institute||Decatur, Illinois 62526|
|Oncology Care Associates, P.L.L.C.||Saint Joseph, Michigan 49085|
|LaGrange Memorial Hospital||LaGrange, Illinois 60525|