A Phase I/II Study Of OSI-774 In Combination With Oxaliplatin, And 5-Fluourouracil In Patients With Metastatic Colorectal Carcinoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed colon or rectal cancer

- Metastatic or unresectable disease

- Unidimensionally measurable disease required for phase II only

- At least 20 mm by x-ray, CT scan, MRI, or photography

- The following are not considered measurable:

- Pleural effusion or ascites

- Osteoblastic lesions

- Evidence of disease on bone scan alone

- Progressive irradiated lesions alone

- Bone marrow involvement

- Brain metastases

- Malignant hepatomegaly by physical exam alone

- Chemical markers (e.g., carcinoembryonic antigen)

- Recurrent disease after surgery or radiotherapy is considered measurable as long
as the following criteria are met:

- At least 4 weeks since prior surgery or radiotherapy

- Measurable disease exists outside the radiation port or clear progression
exists within the radiation port

- Tissue accessible for immunohistochemical evidence of epidermal growth factor
receptor expression from a metastatic site (phase II only)

- No known brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 3 months

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic

- Bilirubin normal

- AST/ALT no greater than 2.5 times upper limit of normal

Renal

- Creatinine normal OR

- Creatinine clearance at least 60 mL/min

Cardiovascular

- No unstable angina pectoris

- No symptomatic congestive heart failure

- No cardiac arrhythmia

- No uncontrolled hypertension (systolic blood pressure greater than 150 mm Hg)

Opthalmic

- No abnormalities of the cornea (e.g., severe dry eye syndrome or Sjogren's syndrome)

- No congenital abnormality (e.g., Fuch's dystrophy)

- No abnormal slit-lamp examination using vital dye (e.g., fluorescein or Bengal-Rose)

- No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear-production
test)

- Mild dry eye syndrome allowed if patient can use artificial tears and ophthalmologist
concurs

Gastrointestinal

- No gastrointestinal tract disease resulting in an inability to take oral medication
or a requirement for IV alimentation

- No active peptic ulcer disease

Other

- Must be able and willing to undergo a mediport insertion

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except previously excised and inactive
basal cell or squamous cell skin cancer

- No prior allergic reactions attributed to compounds of similar chemical or biological
composition to erlotinib or other study drugs (e.g., epidermal growth factor
inhibitors like cetuximab)

- No significant traumatic injury within the past 3 weeks

- No peripheral neuropathy grade 2 or greater

- No ongoing or active infection

- No other uncontrolled concurrent illness that would preclude study entry

- No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- Phase I:

- Prior chemotherapy allowed

- Phase II:

- No prior chemotherapy for metastatic disease

- Prior adjuvant therapy allowed if disease progresses during adjuvant therapy

- No prior oxaliplatin

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy and recovered

Surgery

- See Disease Characteristics

- More than 3 weeks since prior major surgery and recovered

- No prior surgical procedures affecting absorption

Other

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies (commercial or investigational)

- No concurrent combination antiretroviral therapy for HIV-positive patients