Phase II Study of Erlotinib (Tarceva) Alternating With Chemotherapy for Second-line Treatment of Metastatic Colorectal Cancer With Molecular Correlates for p53 Pathway

Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for study entry:

- Age 18-80

- Able to provide informed consent

- Biopsy proven unresectable metastatic adenocarcinoma of the colon or rectum

- Documented progression on prior first-line oxaliplatin-based or irinotecan-based
regimen for metastatic colorectal cancer

- Radiographically measurable disease with at least one bidimensionally measurable
lesion of > 1 cm

- Prior first-line regimen must have been completed at least 4 weeks prior to study
treatment

- Use of biologic agents with first-line chemotherapy permitted

- Previous adjuvant regimens must have been greater than 6 months before inclusion

- Adequate organ function including bone marrow, liver and renal function as defined by
the following values: absolute neutrophil count > 1500/uL; Hgb > 9 g/dL; platelets >
90,000/uL; INR < 1.8 (unless in therapeutic range if taking warfarin or other
warfarin-derivative anticoagulants and are being monitored regularly for changes in
prothrombin time or INR); bilirubin < 2X ULN; alkaline phosphatase < 3X ULN; AST/ALT
< 5X ULN; serum creatinine < 1.5 X ULN

- ECOG status < 2

Exclusion Criteria:

Patients meeting any of the following criteria are ineligible for study entry:

- Prior second-line chemotherapy regimens for colorectal cancer

- Prior treatment with erlotinib or gefitinib

- CNS metastasis

- Second malignancies less than 5 years prior to enrollment. Completely resected basal
or squamous cell carcinoma of the skin is allowed.

- Untreated/unresolved bowel obstruction

- Inability to take oral mediations

- HIV positive

- Pregnancy

- Other uncontrolled medical illnesses

- Current diarrhea > grade 2

- Symptomatic angina or uncontrolled congestive heart failure