Effect of Panitumumab on the Pharmacokinetics of Irinotecan

A Phase I, Open-label Study to Determine the Effect of Panitumumab on the Pharmacokinetics of Irinotecan in Subjects With Unresectable Metastatic Colorectal Cancer

The primary objective of this study is to determine if panitumumab affects the pharmacokinetic (PK) profile 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