A Phase I/II Study of Capecitabine (XELODA®, Roche) Plus Oxaliplatin (Eloxatin®, Sanofi) Plus ZD 1893 (IRESSA®) in the Treatment of Metastatic Colorectal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed* colorectal cancer

- Metastatic disease

- The site of the primary tumor must have been confirmed endoscopically,
radiologically, or surgically to be the colon or rectum NOTE: *Confirmation is
not required for recurrent metastatic disease unless an interval of > 5 years
has elapsed between the initial primary surgery and the development of
metastases

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan

- No CNS metastases

PATIENT CHARACTERISTICS:

Age

- 18 to 80

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL (transfusion allowed)

Hepatic

- AST and ALT ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ ULN

- No unstable or uncompensated hepatic disease

Renal

- Creatinine < 1.5 times ULN OR

- Creatinine clearance > 60 mL/min

- No unstable or uncompensated renal disease

Cardiovascular

- No unstable or uncompensated cardiac disease

Pulmonary

- No evidence of clinically active interstitial lung disease

- Asymptomatic patients with chronic stable radiographic changes are eligible

- No unstable or uncompensated respiratory disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- No known hypersensitivity to gefitinib or any of its excipients

- No known hypersensitivity to platinum compounds, fluorouracil, or capecitabine

- No severe or uncontrolled systemic disease

- Able to receive oral medication

- No known dihydropyrimidine dehydrogenase (DPD) deficiency

- No known peripheral neuropathy ≥ grade 1

- Absence of deep tendon reflexes as the sole neurological abnormality allowed

- No other significant clinical disorder or laboratory finding that would preclude
study participation

- No other malignancy within the past 5 years except basal cell skin cancer or
carcinoma in situ of the cervix (phase II only)

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- At least 4 weeks since prior chemotherapy for metastatic colorectal cancer (phase I)

- No prior chemotherapy for metastatic disease (phase II)

- Prior fluorouracil and leucovorin calcium in the adjuvant setting allowed
provided the last treatment was administered more than 6 months before the
development of metastatic disease

- No prior irinotecan and oxaliplatin (phase II)

Endocrine therapy

- Not specified

Radiotherapy

- No concurrent radiotherapy for colorectal cancer

Surgery

- See Disease Characteristics

- More than 4 weeks since prior major surgery (e.g., laparotomy)

Other

- Recovered from all prior therapy (no unresolved chronic toxicity > grade 2)

- More than 4 weeks since prior investigational drugs

- No prior epidermal growth factor receptor inhibitor therapy (phase II)

- No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum
perforatum (St. John's wort)

- No other concurrent investigational drugs

- No other concurrent systemic therapy for colorectal cancer