Clinical trial NCT00563316: Effect of Panitumumab on the Pharmacokinetics of Irinotecan
Official title: A Phase I, Open-label Study to Determine the Effect of Panitumumab on the Pharmacokinetics of Irinotecan in Subjects With Unresectable Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Keywords: colorectal cancer
chemotherapy
cancer
metastatic
irinotecan
EGFr
epidermal growth factor
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-11-26
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Irinotecan
timeFrame: Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).
measure: Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUCinf) for Irinotecan
timeFrame: Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).
measure: Area Under the Plasma Concentration-time Curve From the Time of the Last Quantifiable Concentration (AUClast) for Irinotecan
timeFrame: Predose and at 10 minutes, and 0.5, 1, 2, 4, 8, 24, 48, and 72 hours after the end of the irinotecan infusion at cycle 1 (irinotecan alone, week 1 day 1) and cycle 2 (irinotecan with panitumumab, week 3, day 1).
measure: Number of Participants With Clinically Significant Adverse Events (AEs)
timeFrame: The reporting time frame for Adverse Events is from first dose date to 30 days since the last dose date, until the data cut-off date of 16 July 2009. The median time frame is 5.7 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Billings
country: United States
facility: Research Site
state: Montana
city: Billings
country: United States
facility: Research Site
state: Montana
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Yang BB, Wu CY, Chen E, Infante JR, Chen A, Gao B, Smith B, Litten J, Kennecke H. Pharmacokinetics of Irinotecan With and Without Panitumumab Coadministration in Patients With Metastatic Colorectal Cancer. Clin Pharmacol Drug Dev. 2013 Jul;2(3):205-12. doi: 10.1002/cpdd.35. Epub 2013 May 15.