Effect of Panitumumab on the Pharmacokinetics of Irinotecan

Inclusion Criteria:

- Pathologically confirmed unresectable metastatic colorectal cancer (mCRC) which has
progressed on at least one prior 5-fluorouracil (5FU)-containing chemotherapy regimen

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Life expectancy of ≥ 3 months as documented by the investigator

- Baseline actual body weight ≤ 160 kg

- Competent to comprehend, sign, and date a written Institutional Review Board (IRB)
approved informed consent form before any study-specific procedures are performed

Exclusion Criteria:

- Treatment with radiotherapy ≤ 14 days before enrollment. Patients must have recovered
from all radiotherapy-related toxicities

- Known presence of central nervous systems (CNS) metastases

- Any prior malignancy (except for non-melanomatous skin cancer or in situ cervical
cancer) other than the study disease, unless treated with curative intent with no
evidence of disease ≤ 2 years before enrollment

- History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or
evidence of interstitial lung disease on baseline chest computed tomography (CT) scan

- Active inflammatory bowel disease or other bowel disease causing chronic diarrhea
(defined as > Common Terminology Criteria for Adverse Events (CTCAE version 3) grade
2

- Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) ≤ 1 year before enrollment

- UGT1A1*28 TA7/7, TA7/8, TA8/8 genetic polymorphisms; Gilbert's Disease

- Treatment with CYP3A4 enzyme inhibiting or inducing medications ≤ 2 weeks before
enrollment

- Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab)
or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib,
lapatinib)

- Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved
proteins/antibodies (eg, bevacizumab) ≤ 30 days before enrollment

- Subjects requiring immunosuppressive agents (eg, methotrexate and cyclosporine),
however corticosteroids are allowed

- Major surgery < 28 days prior to enrollment or minor surgery (excluding catheter
placement) < 14 days before enrollment