Effect of Panitumumab on the Pharmacokinetics of Irinotecan

March 14, 2016 updated by: Amgen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Research Site
      • Vancouver, British Columbia, Canada
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Site
      • Toronto, Ontario, Canada
        • Research Site
  • United States
    • Montana
      • Billings, Montana, United States
        • Research Site
      • Billings, Montana, United States, 59107
        • Research Site
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Research Site
      • Chapel Hill, North Carolina, United States
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
      • Philadelphia, Pennsylvania, United States
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site
      • Nashville, Tennessee, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Panitumumab + Irinotecan
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.
Drug: Panitumumab
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.
Other Names:
  • Vectibix
Drug: Irinotecan
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.
Other Names:
  • Camptosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
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).
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.
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).
Area Under the Plasma Concentration-time Curve From the Time of Dosing to Infinity (AUCinf) for Irinotecan
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).
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.
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).
Area Under the Plasma Concentration-time Curve From the Time of the Last Quantifiable Concentration (AUClast) for Irinotecan
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).
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.
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).
Number of Participants With Clinically Significant Adverse Events (AEs)
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.

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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

November 21, 2007

First Submitted That Met QC Criteria

November 21, 2007

First Posted (Estimate)

November 26, 2007

Study Record Updates

Last Update Posted (Estimate)

April 12, 2016

Last Update Submitted That Met QC Criteria

March 14, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20062010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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