Phase II Study of First-Line Capecitabine and Cetuximab for Treatment of Metastatic Colorectal Cancer in Elderly Patients and/or Those With Multiple Comorbidities Unable to Receive Chemotherapy Doublets

Inclusion Criteria

Inclusion Criteria

- Histologically or cytologically proven diagnosis of locally extensive or metastatic
colorectal cancer, not amenable to curative therapy.

- No prior therapy for metastatic disease. Only 5-fluorouracil and leucovorin
chemotherapy in the adjuvant setting will be allowed and the last treatment was given
more then 6 months prior to metastatic disease development.

- Patients with an ECOG performance score of 2 AND/OR Charlson comorbidity index of ³
4.

- Patients must be documented by the physician to be medically unable to tolerate
oxaliplatin and/or irinotecan based chemotherapy.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as ³
20 mm with conventional techniques or as ³10 mm with spiral CT scan.

- Life expectancy of greater than 3 months.

- Laboratory values showing adequate organ function prior to going on-study:

- Absolute neutrophil count (ANC) ≥ 2.5 x 109/L

- Platelets (PLT) 100 x 109/L

- Hemoglobin 9g/dl (with or without transfusion)

- Metabolic:Calculated creatinine clearance > 50 ml/min

- Total Bilirubin £ 1.5 x Upper limit of normal (ULN)

- AST £ 3 x ULN

- Patient should be able to ingest oral medication.

- Ability to understand and sign an approved informed consent.

Exclusion Criteria

- Patients with uncontrolled systemic disease other than the patient's colorectal
cancer (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal
disease) for which the patient was admitted to the hospital within the prior month.
Patients with stable respiratory, cardiac, hepatic or renal disease may participate
subject to the guidelines in the eligibility criteria above.

- Presence of dementia or delirium.

- Unable to eat, dress, bathe or use the toilet independently. The patient must be
able to ambulate independently unless limited by arthritis or musculoskeletal
condition.

- Patients with active gastritis within the last 3 months prior to study entry.

- No synchronous or prior malignancy other than non-melanomatous skin cancer or insitu
carcinoma of the cervix, unless disease free > 3 years.

- Known dihydropyrimidine dehydrogenase (DPD) deficiency.

- Pregnant women are ineligible as treatment involves unforeseeable risks to the
participant and to the embryo or fetus. Women must either be not of child bearing
potential or have a negative pregnancy test within 7 days of treatment. Patients are
considered not of child bearing potential if they are surgically sterile (they have
undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or
they are postmenopausal. Men and women must be willing to use adequate birth control
measures to prevent contraception.

- Inability to or unwillingness to comply with protocol defined treatment and
assessments.

- Prior therapy that specifically and directly targets the EGFR pathway.

- Prior severe infusion reaction to a monoclonal antibody.

- Any concurrent chemotherapy not indicated in the study protocol or any other
investigational agent(s).

- Patients ingesting herbal supplements, botanicals or vitamins in excess of
recommended daily dose must be willing to stop their use, 1 week prior to study
entry.