A Study of Mitomycin C, Irinotecan, and Cetuximab

We propose a phase II trial which combines mitomycin C, irinotecan and cetuximab in patients
with previously treated metastatic colorectal cancer with wild type non mutated K-Ras. The
goals of this investigation are to develop an effective systemic therapy for previously
treated patients with CRC with wild type K-Ras, to further explore the relationship of
mitomycin C induced topoisomerase 1 gene expression and response to irinotecan, and to
define and characterize the biology of cetuximab induced skin rash.

Inclusion Criteria:

1. Pathologic diagnosis of colorectal cancer.

2. Clinical and/or radiologic evidence of metastatic disease.

3. One previous systemic treatment for metastatic disease.

4. Age > 18.

5. Presence of at least one measurable lesion.

6. Adequate hematopoetic (absolute neutrophil count > 1500/mm3, platelet count >
100,000/mm3), renal (serum creatinine < 1.5 mg/dl), and hepatic function (bilirubin <
1.5 and transaminases < 5.0 x upper normal limit).

7. ECOG performance status 0-2.

8. Life expectancy > 3 months.

9. Patients must be informed of the investigational nature of this study and provide
written informed consent in accordance with the institutional and federal guidelines
prior to the initiation of therapy.

Exclusion Criteria:

1. No recognized brain metastasis.

2. No previous treatment with mitomycin C or cetuximab.

3. No other systemic malignancy requiring treatment within the past one year.

4. Pregnant or lactating women may not participate. Women/men of reproductive potential
must agree to use an effective contraceptive method.

5. Patients must have no other serious medical or psychiatric illness that would limit
the ability of the patient to receive protocol therapy or provide informed consent.