A Phase II Study Of OSI-774 In Metastatic Colorectal Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that
is not curable with conventional therapy

- Recurrent or metastatic disease

- At least 1 unidimensionally measurable lesion

- At least 20 mm by conventional techniques

- At least 10 mm by spiral CT scan

- Target lesion must not be in a previously irradiated field unless progression of
this lesion has been documented

- No known brain metastases

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- More than 3 months

- WBC at least 1,500/mm^3

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

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

- Bilirubin no greater than 1.25 times upper limit of normal (ULN)

- AST or ALT no greater than 3 times ULN (5 times ULN if liver metastases present)

- Creatinine no greater than 1.25 times ULN

- Creatinine clearance at least 50 mL/min

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

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

- No active peptic ulcer disease

- No unresolved complete or subacute bowel obstruction

- No severe enteropathy that would interfere with absorption of study drug

- No abnormalities of the cornea:

- Dry eye syndrome or Sjogren's syndrome

- Congenital abnormality (e.g., Fuch's dystrophy)

- Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or
Bengal-Rose)

- Abnormal corneal sensitivity test (Schirmer test or similar tear production
test)

- No significant traumatic injury within the past 21 days

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study

- No other concurrent uncontrolled illness that would preclude study

- No other malignancy within the past 3 years except curatively treated nonmelanoma
skin cancer or carcinoma in situ of the cervix

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No more than 1 prior chemotherapy regimen for metastatic disease with either
fluorouracil (5-FU) and oxaliplatin or 5-FU and a topoisomerase inhibitor (e.g.,
irinotecan), OR 5-FU (or other single-agent fluoropyrimidine, such as capecitabine)
followed by irinotecan for advanced disease

- Prior adjuvant chemotherapy allowed

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

- At least 3 weeks since prior major surgery

- No prior surgical procedures affecting absorption

- No prior epidermal growth factor receptor-targeting therapy

- No other concurrent investigational therapies

- No other concurrent anticancer therapy

- No concurrent combination anti-retroviral therapy for HIV-positive patients

- No concurrent warfarin

- Low molecular weight heparin allowed