Gefitinib in Treating Patients With Recurrent Metastatic Colorectal Cancer

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of recurrent metastatic colorectal cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of two different doses of gefitinib in treating patients who have recurrent metastatic colorectal cancer.

OBJECTIVES:

* Determine the 4-month progression-free survival rate in patients with recurrent metastatic colorectal adenocarcinoma treated with gefitinib.
* Determine the objective tumor response rate, progression, and overall survival of patients treated with this drug.
* Determine the toxicity of this drug in these patients.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to ECOG performance status (0-1 vs 2), baseline serum CEA (less than 5 mg/L vs at least 5 mg/L), and number of metastatic sites (1 vs 2 or more). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral gefitinib once daily (twice daily on day 1 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive a higher dose of oral gefitinib as in arm I. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically or cytologically proven adenocarcinoma of the colon or rectum
* Measurable disease
* Evidence of new or progressive metastatic disease within 6 months of last treatment
* Must have received prior systemic treatment with fluorouracil (and/or its analogs, with or without leucovorin calcium or levamisole) and irinotecan in the adjuvant or metastatic setting
* Metastatic tumor site accessible for biopsy
* No known brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* More than 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* AST or ALT no greater than 2.5 times ULN (5 times ULN if tumor involvement of the liver)

Renal:

* Creatinine no greater than 1.5 times ULN OR
* Creatinine clearance at least 60 mL/min

Cardiovascular:

* No New York Heart Association class III or IV heart disease
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No ongoing active or uncontrolled infections
* Other prior malignancies allowed provided prior therapy is discontinued and no evidence of disease
* No other uncontrolled illness or psychiatric illness/social situations that would preclude study
* Must be able to take and retain oral medications

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior signal transduction inhibitors (e.g., vascular endothelial growth factor-, vascular endothelial growth factor receptor-, and epidermal growth factor receptor-targeted agents) for colorectal cancer

Chemotherapy:

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy and recovered
* No other prior cytotoxic chemotherapy (e.g., oxaliplatin) for colorectal cancer

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 4 weeks since prior radiotherapy and recovered

Surgery:

* Not specified

Other:

* No other prior systemic therapy for colorectal cancer
* No other prior investigational or approved agents for colorectal cancer
* No other concurrent investigational agents
* No concurrent antiretroviral therapy for HIV-positive patients