A Randomized Phase II Trial of Two Dose Levels of ZD1839 (Iressa) (NSC 715055, IND 61187) in Patients With Recurrent Colorectal Adenocarcinoma

Inclusion 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