A Phase I, Pharmacological, and Biological Study of OSI-774 in Combination With FOLFOX 4 (5-FU, Leucovorin, and Oxaliplatin) and Bevacizumab (Avastin) in Patients With Advanced Colorectal Cancer

Previous oxaliplatin therapy for metastatic disease; (prior adjuvant therapy with oxaliplatin is allowed as long as 120 days have elapsed since the last oxaliplatin treatment)

Less than 120 days elapsed time between chemotherapy treatment for adjuvant disease and enrollment onto this protocol or less than 28 days between therapy for metastatic disease and enrollment onto this protocol

Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774, oxaliplatin, 5-FU, or leucovorin

Patients with a significant neuropathy (greater than grade 2) not controlled despite medications

Prior treatment with EGFR targeting therapies

Major surgery or significant traumatic injury occurring within 28 days prior to treatment; all surgical wounds must be healed

Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)

Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant women are excluded from this study because OSI-774 is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with OSI-774; because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \<10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:

* Bone lesions;

* Leptomeningeal disease;

* Ascites;

* Pleural/pericardial effusion;

* Inflammatory breast disease;

* Lymphangitis cutis/pulmonis;

* Abdominal masses that are not confirmed and followed by imaging techniques;

* Cystic lesions

Patients without sufficient central venous access for therapy

Patients with thromboembolic events (MI, TIA, stroke, or angina) occurring within the past 6 months prior to the start of therapy

What this study is about