Effect of Panitumumab on the Pharmacokinetics of Irinotecan

NCT00563316 | Completed Phase 1 Results

• 1 other identifier: 20062010
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 12

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Keywords

colorectal cancer; chemotherapy; cancer; metastatic; irinotecan; EGFr; epidermal growth factor

Outcome Measures

Primary Outcomes (4)

• 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.

  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

  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

  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)

  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.

Study Arms (1)

Panitumumab + Irinotecan

EXPERIMENTAL

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; Drug: Irinotecan

Interventions

Panitumumab DRUG

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.

Also known as: Vectibix

Panitumumab + Irinotecan

Irinotecan DRUG

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.

Also known as: Camptosar

Panitumumab + Irinotecan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

Research Site

Billings, Montana, 59107, United States

Location

Research Site

Billings, Montana, United States

Location

Research Site

Chapel Hill, North Carolina, 27599, United States

Location

Research Site

Chapel Hill, North Carolina, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Nashville, Tennessee, United States

Location

Research Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Research Site

Vancouver, British Columbia, Canada

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 27121781 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

Panitumumab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2007
• First Posted: November 26, 2007
• Study Start: March 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: June 1, 2010
• Last Updated: April 12, 2016
• Results First Posted: April 12, 2016

Record last verified: 2016-03

Locations

CA (4); US (8)