Effect of Panitumumab on the Pharmacokinetics of Irinotecan
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Panitumumab
Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring colorectal cancer, chemotherapy, cancer, metastatic, irinotecan, EGFr, epidermal growth factor
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panitumumab + Irinotecan
Arm Description
Participants received panitumumab 6 mg/kg and irinotecan 180 mg/m² administered by intravenous (IV) infusion every 2 weeks until disease progression or intolerance of panitumumab, irinotecan or both.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the Cmax of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured. Plasma samples were assayed by a validated high performance liquid chromatography (HPLC)-fluorescence method for the measurement of irinotecan. The lower limit of quantitation (LLOQ) was 2 ng/mL.
Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUCinf) for Irinotecan
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUCinf of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.
Area Under the Plasma Concentration-time Curve From the Time of the Last Quantifiable Concentration (AUClast) for Irinotecan
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUClast of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.
Number of Participants With Clinically Significant Adverse Events (AEs)
Adverse events of special interest include infusion reactions, integument toxicities, diarrhea, stomatitis, hypomagnesemia, and pulmonary, vascular, and cardiac toxicities. Infusion reactions were defined as 1. Prespecified signs and symptoms indicating a possible infusion reaction (derived from Common Terminology Criteria for Adverse Events (CTCAE) definitions of allergic reaction/hypersensitivity and cytokine release syndrome/acute infusion reaction) with onset day coincident with any study drug infusion and which resolved the day of, or the day after, onset; 2. incidence of AE with terms consistent with the panitumumab US package insert (USPI) (any event within 24 hours of an infusion during the clinical study described as allergic reaction or anaphylactoid reaction, or any event occurring on the first day of dosing described as allergic reaction, anaphylactoid reaction, fever, chills, or dyspnea).
Data are summarized overall and by treatment phase.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00563316
Brief Title
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
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
The primary objective of this study is to determine if panitumumab affects the pharmacokinetic (PK) profile of irinotecan.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
colorectal cancer, chemotherapy, cancer, metastatic, irinotecan, EGFr, epidermal growth factor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panitumumab + Irinotecan
Arm Type
Experimental
Arm Description
Participants received panitumumab 6 mg/kg and irinotecan 180 mg/m² administered by intravenous (IV) infusion every 2 weeks until disease progression or intolerance of panitumumab, irinotecan or both.
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix
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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
Description
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the Cmax of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured. Plasma samples were assayed by a validated high performance liquid chromatography (HPLC)-fluorescence method for the measurement of irinotecan. The lower limit of quantitation (LLOQ) was 2 ng/mL.
Time Frame
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).
Title
Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUCinf) for Irinotecan
Description
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUCinf of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.
Time Frame
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).
Title
Area Under the Plasma Concentration-time Curve From the Time of the Last Quantifiable Concentration (AUClast) for Irinotecan
Description
To analyze the effect, if any, that panitumumab had on the pharmacokinetics of irinotecan, the AUClast of irinotecan administered alone (Cycle 1) and with concomitant panitumumab (Cycle 2) was measured.
Time Frame
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).
Title
Number of Participants With Clinically Significant Adverse Events (AEs)
Description
Adverse events of special interest include infusion reactions, integument toxicities, diarrhea, stomatitis, hypomagnesemia, and pulmonary, vascular, and cardiac toxicities. Infusion reactions were defined as 1. Prespecified signs and symptoms indicating a possible infusion reaction (derived from Common Terminology Criteria for Adverse Events (CTCAE) definitions of allergic reaction/hypersensitivity and cytokine release syndrome/acute infusion reaction) with onset day coincident with any study drug infusion and which resolved the day of, or the day after, onset; 2. incidence of AE with terms consistent with the panitumumab US package insert (USPI) (any event within 24 hours of an infusion during the clinical study described as allergic reaction or anaphylactoid reaction, or any event occurring on the first day of dosing described as allergic reaction, anaphylactoid reaction, fever, chills, or dyspnea).
Data are summarized overall and by treatment phase.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Billings
State/Province
Montana
ZIP/Postal Code
59107
Country
United States
Facility Name
Research Site
City
Billings
State/Province
Montana
Country
United States
Facility Name
Research Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Research Site
City
Chapel Hill
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
27121781
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Effect of Panitumumab on the Pharmacokinetics of Irinotecan
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