Gefitinib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors or Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title: 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)

Status Completed

Clinical Trial Summary

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug with gefitinib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of gefitinib and oxaliplatin combined with leucovorin and fluorouracil in treating patients who have advanced solid tumors or colorectal cancer.

Clinical Trial Description

OBJECTIVES:

• 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 these patients.

• 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 II dose.

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 months. ;

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

• NCT number: NCT00025142
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 2
• Start date: July 2001
• Completion date: November 2006