Effect of Panitumumab on the Pharmacokinetics of Irinotecan
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Panitumumab; Irinotecan
Intervention description: The first infusion of panitumumab will occur on Cycle 1 Day 4. On Cycle 2 Day 1, panitumumab will be administered on the same day as irinotecan and every 2 weeks thereafter.; The first infusion of irinotecan will occur on Cycle 1 Day 1. Irinotecan will be administered on the same day as panitumumab on Cycle 2 Day 1 and every 2 weeks thereafter.
Intervention MeSH terms: Irinotecan; Panitumumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: colorectal cancer; chemotherapy; cancer; metastatic; irinotecan; EGFr; epidermal growth factor

Summary:

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

Eligibility criteria:

        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