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Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

Primary Purpose

Rectal Cancer, Colon Cancer

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
FOLFOX-4
AMG 706
Panitumumab (Part 1a only)
FOLFIRI
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring AMG 706, Panitumumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

For complete inclusion and exclusion criteria, please refer to the investigator. Inclusion Criteria Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form Diagnosis of metastatic colorectal adenocarcinoma (may have received 1 prior chemotherapy regimen for metastatic CRC) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematological function Adequate renal function Adequate hepatic function Life expectancy of greater than or equal to 3 months as documented by the investigator Exclusion Criteria: More than 1 prior chemotherapy regimen for metastatic CRC Central nervous system (CNS) metastases History of venous thrombosis Myocardial infarction, cerebrovascular accident, transient ischemic attack, grade 2 or greater peripheral vascular disease, congestive heart failure, ongoing arrhythmias requiring medication, or unstable angina within 1 year before study enrollment History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan Average systolic blood pressure > 150mm Hg or average diastolic blood pressure of > 90mm Hg Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000) Systemic chemotherapy within 28 days before study enrollment Major surgery within 28 days or minor surgery within 7days of study enrollment History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia) Female and male subjects of childbearing potential not using adequate contraceptive precautions Participation in therapeutic clinical trials within 30 days before study enrollment Not recovered from all previous therapies Clinically significant open would, ulcer or fracture Any co-morbid medical condition that would increase the risk of toxicity

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm 10

    Arm 11

    Arm 12

    Arm 13

    Arm 14

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part 2 AMG 706 (MTD) + FOLFOX-4

    125 mg QD AMG 706 + FOLFOX-4

    50 mg QD AMG706 + panitumumab + FOLFIRI

    Part 2 AMG 706 (MTD) + FOLFIRI

    100 mg QD AMG 706 + FOLFIRI

    75 mg QD AMG 706 + panitumumab + FOLFOX-4

    75 mg BID AMG 706 + panitumumab + FOLFIRI

    125 mg QD AMG 706 + panitumumab + FOLFIRI

    125 mg QD AMG 706 + FOLFIRI

    100 mg QD AMG 706 + panitumumab + FOLFIRI

    75 mg QD AMG 706 + FOLFOX-4

    100 mg QD AMG 706 + FOLFOX-4

    50 mg QD AMG 706 + panitumumab + FOLFOX-4

    75 mg QD AMG706 + panitumumab + FOLFIRI

    Arm Description

    Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4

    125 mg QD AMG 706 + FOLFOX-4

    50 mg QD AMG706 + panitumumab + FOLFIRI

    Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI

    100 mg AMG 706 + FOLFIRI

    75 mg QD AMG 706 + panitumumab + FOLFOX-4

    75 mg BID AMG 706 + panitumumab + FOLFIRI

    125 mg QD AMG 706 + panitumumab + FOLFIRI

    125 mg QD AMG 706 + FOLFIRI

    100 mg QD AMG 706 + panitumumab + FOLFIRI

    75 mg QD AMG 706 + FOLFOX-4

    100 mg QD AMG 706 + FOLFOX-4

    50 mg QD AMG 706 + panitumumab + FOLFOX-4

    75 mg QD AMG706 + panitumumab + FOLFIRI

    Outcomes

    Primary Outcome Measures

    Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
    Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
    Part 2 - The overall objective tumor response rate (complete and partial response) in subjects treated with AMG 706 (at the dose determined in Part 1b), with either the FOLFIRI or FOLFOX-4 chemotherapy regimen

    Secondary Outcome Measures

    Part 1a - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with panitumumab and AMG 706
    Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706
    Part 1a - The objective tumor response rate (complete and partial response) throughout the study
    Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
    Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706
    Part 2 - Duration of response: (Calculated for only those subjects who respond)
    Part 2 - Time-to-progression
    Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706
    Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706
    Part 1b - The objective tumor response rate (complete and partial response) throughout the study
    Part 2 - Overall survival
    Part 2 - The incidence of adverse events and clinical laboratory abnormalities
    Part 2 - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen (at a subset of the study centers with the capabilities to draw, ship and process PK samples)
    Exploratory - Potential biomarker development based on assessment of blood cells, tumor cells, and urine and the proposed mechanism of action of study drugs, and response
    Exploratory - The effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to investigational products (separate informed consent)
    Part 2 - Progression-free survival time
    Part 2 - Incidence of subjects undergoing resection of metastases for curative intent
    Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
    Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Part 1a - The incidence of HAPA response following panitumumab administration
    Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706

    Full Information

    First Posted
    January 18, 2005
    Last Updated
    September 13, 2012
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00101894
    Brief Title
    Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer
    Official Title
    An Open-Label, Dose-Finding Study to Evaluate the Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    December 2004 (undefined)
    Primary Completion Date
    April 2010 (Actual)
    Study Completion Date
    December 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to characterize the safety and tolerability of AMG 706 plus panitumumab when administered with either FOLFIRI or FOLFOX4 chemotherapy regimens. This is a Phase 1b clinical study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rectal Cancer, Colon Cancer
    Keywords
    AMG 706, Panitumumab

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    119 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 2 AMG 706 (MTD) + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4
    Arm Title
    125 mg QD AMG 706 + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    125 mg QD AMG 706 + FOLFOX-4
    Arm Title
    50 mg QD AMG706 + panitumumab + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    50 mg QD AMG706 + panitumumab + FOLFIRI
    Arm Title
    Part 2 AMG 706 (MTD) + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI
    Arm Title
    100 mg QD AMG 706 + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    100 mg AMG 706 + FOLFIRI
    Arm Title
    75 mg QD AMG 706 + panitumumab + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    75 mg QD AMG 706 + panitumumab + FOLFOX-4
    Arm Title
    75 mg BID AMG 706 + panitumumab + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    75 mg BID AMG 706 + panitumumab + FOLFIRI
    Arm Title
    125 mg QD AMG 706 + panitumumab + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    125 mg QD AMG 706 + panitumumab + FOLFIRI
    Arm Title
    125 mg QD AMG 706 + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    125 mg QD AMG 706 + FOLFIRI
    Arm Title
    100 mg QD AMG 706 + panitumumab + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    100 mg QD AMG 706 + panitumumab + FOLFIRI
    Arm Title
    75 mg QD AMG 706 + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    75 mg QD AMG 706 + FOLFOX-4
    Arm Title
    100 mg QD AMG 706 + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    100 mg QD AMG 706 + FOLFOX-4
    Arm Title
    50 mg QD AMG 706 + panitumumab + FOLFOX-4
    Arm Type
    Experimental
    Arm Description
    50 mg QD AMG 706 + panitumumab + FOLFOX-4
    Arm Title
    75 mg QD AMG706 + panitumumab + FOLFIRI
    Arm Type
    Experimental
    Arm Description
    75 mg QD AMG706 + panitumumab + FOLFIRI
    Intervention Type
    Drug
    Intervention Name(s)
    FOLFOX-4
    Intervention Description
    The FOLFOX-4 regimen will be administered every 2 weeks as follows: Day 1: oxaliplatin (ELOXATIN™) 85 mg/m2 IV infusion and leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion given over 120 ± 10 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed by 5-FU 600 mg/m2 IV infusion as a 22-hour ± 2 hours continuous infusion Day 2: leucovorin racemate 200 mg/m2 (or 100 mg/m2 l-LV) IV infusion over 120 ± 10 minutes, followed by 5-FU 400 mg/m2 IV bolus given over 2 to 4 minutes, followed
    Intervention Type
    Drug
    Intervention Name(s)
    AMG 706
    Intervention Description
    AMG 706 is a small organic molecule that has been shown in preclinical pharmacology studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively inhibiting all known VEGF receptors, PDGF receptor, and Kit.
    Intervention Type
    Biological
    Intervention Name(s)
    Panitumumab (Part 1a only)
    Intervention Description
    Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
    Intervention Type
    Drug
    Intervention Name(s)
    FOLFIRI
    Intervention Description
    Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-week cycle. Leucovorin will be administered over 2 hours ± 15 minutes during the irinotecan infusion but without mixing, immediately followed by a 5-FU bolus and a 5-FU 46-hour ± 2-hour continuous intravenous infusion.
    Primary Outcome Measure Information:
    Title
    Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
    Time Frame
    First 2 cycles
    Title
    Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
    Time Frame
    First 2 cycles
    Title
    Part 2 - The overall objective tumor response rate (complete and partial response) in subjects treated with AMG 706 (at the dose determined in Part 1b), with either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Time Frame
    Every 8 weeks (+/- 7 days)
    Secondary Outcome Measure Information:
    Title
    Part 1a - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with panitumumab and AMG 706
    Time Frame
    Cycle 1 and 2 (Days 1, 2, 3)
    Title
    Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706
    Time Frame
    Cycle 1 and 2 (Day 1)
    Title
    Part 1a - The objective tumor response rate (complete and partial response) throughout the study
    Time Frame
    Every 6 to 8 weeks
    Title
    Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
    Time Frame
    Every visit
    Title
    Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Time Frame
    Cycle 2 (Day 1-2), Cycle 3 (Day 1)
    Title
    Part 1b - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with AMG 706
    Time Frame
    Cycle 1 and 2 (Day 3)
    Title
    Part 2 - Duration of response: (Calculated for only those subjects who respond)
    Time Frame
    Time from first objective tumor response (subsequently confirmed at least 4 weeks later) to objective disease progression or death.
    Title
    Part 2 - Time-to-progression
    Time Frame
    Time from first dose of investigational product to objective disease progression or death due to disease progression.
    Title
    Part 1b - The PK of irinotecan (and its active metabolite SN38) when administered as a part of the FOLFIRI regimen with AMG 706
    Time Frame
    Cycle 1 and 2 (Days 1, 2, 3)
    Title
    Part 1b- The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with AMG 706
    Time Frame
    Cycle 1 and 2 (Day 1)
    Title
    Part 1b - The objective tumor response rate (complete and partial response) throughout the study
    Time Frame
    Every 8 weeks (+/- 7 days)
    Title
    Part 2 - Overall survival
    Time Frame
    Time from first dose of investigational product to death. Subjects who have not died while on study or are lost to follow-up will be censored at their last contact date. (Time on study plus 36 months of long term follow-up)
    Title
    Part 2 - The incidence of adverse events and clinical laboratory abnormalities
    Time Frame
    Every visit
    Title
    Part 2 - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen (at a subset of the study centers with the capabilities to draw, ship and process PK samples)
    Time Frame
    Cycles 2, 4, 7, and every 3 subsequent cycles (Day 1)
    Title
    Exploratory - Potential biomarker development based on assessment of blood cells, tumor cells, and urine and the proposed mechanism of action of study drugs, and response
    Time Frame
    Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment
    Title
    Exploratory - The effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to investigational products (separate informed consent)
    Time Frame
    Day 1 of cycles 1 and 2, and within 7 days of a radiographic assessment
    Title
    Part 2 - Progression-free survival time
    Time Frame
    Time from first dose of investigational product to objective disease progression or death, subjects who have not progressed or died while on study will be censored at their last evaluable assessment date.
    Title
    Part 2 - Incidence of subjects undergoing resection of metastases for curative intent
    Time Frame
    As needed
    Title
    Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
    Time Frame
    Every visit
    Title
    Part 1a - The PK of AMG 706 when administered with panitumumab and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Time Frame
    Cycle 2 (Day 1-2), Cycle 3 (Day 1)
    Title
    Part 1a - The serum concentration of panitumumab when administered with AMG 706 and either the FOLFIRI or FOLFOX-4 chemotherapy regimen
    Time Frame
    Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 4 (Day 1)
    Title
    Part 1a - The incidence of HAPA response following panitumumab administration
    Time Frame
    Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study
    Title
    Part 1a - The PK of 5-FU when administered as a part of the FOLFIRI or FOLFOX-4 regimen with panitumumab and AMG 706
    Time Frame
    Cycle 1 and 2 (Day 3)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    For complete inclusion and exclusion criteria, please refer to the investigator. Inclusion Criteria Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form Diagnosis of metastatic colorectal adenocarcinoma (may have received 1 prior chemotherapy regimen for metastatic CRC) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematological function Adequate renal function Adequate hepatic function Life expectancy of greater than or equal to 3 months as documented by the investigator Exclusion Criteria: More than 1 prior chemotherapy regimen for metastatic CRC Central nervous system (CNS) metastases History of venous thrombosis Myocardial infarction, cerebrovascular accident, transient ischemic attack, grade 2 or greater peripheral vascular disease, congestive heart failure, ongoing arrhythmias requiring medication, or unstable angina within 1 year before study enrollment History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan Average systolic blood pressure > 150mm Hg or average diastolic blood pressure of > 90mm Hg Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab [Erbitux®] or EMD 72000) Systemic chemotherapy within 28 days before study enrollment Major surgery within 28 days or minor surgery within 7days of study enrollment History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia) Female and male subjects of childbearing potential not using adequate contraceptive precautions Participation in therapeutic clinical trials within 30 days before study enrollment Not recovered from all previous therapies Clinically significant open would, ulcer or fracture Any co-morbid medical condition that would increase the risk of toxicity
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    25772756
    Citation
    Tebbutt N, Kotasek D, Burris HA, Schwartzberg LS, Hurwitz H, Stephenson J, Warner DJ, Chen L, Hsu CP, Goldstein D. Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol. 2015 May;75(5):993-1004. doi: 10.1007/s00280-015-2694-y. Epub 2015 Mar 15.
    Results Reference
    derived
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

    Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer

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