Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer
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
1 other identifier
interventional
119
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2004
Longer than P75 for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2004
CompletedFirst Submitted
Initial submission to the registry
January 18, 2005
CompletedFirst Posted
Study publicly available on registry
January 19, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2011
CompletedSeptember 17, 2012
September 1, 2012
5.3 years
January 18, 2005
September 13, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
First 2 cycles
Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
First 2 cycles
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
Every 8 weeks (+/- 7 days)
Secondary Outcomes (23)
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
Cycle 1 and 2 (Days 1, 2, 3)
Part 1a - The PK of oxaliplatin when administered as a part of the FOLFOX-4 regimen with panitumumab and AMG 706
Cycle 1 and 2 (Day 1)
Part 1a - The objective tumor response rate (complete and partial response) throughout the study
Every 6 to 8 weeks
Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities
Every visit
Part 1b - The PK of AMG 706 when administered with either the FOLFIRI or FOLFOX-4 chemotherapy regimen
Cycle 2 (Day 1-2), Cycle 3 (Day 1)
- +18 more secondary outcomes
Study Arms (14)
Part 2 AMG 706 (MTD) + FOLFOX-4
EXPERIMENTALMaximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4
125 mg QD AMG 706 + FOLFOX-4
EXPERIMENTAL125 mg QD AMG 706 + FOLFOX-4
50 mg QD AMG706 + panitumumab + FOLFIRI
EXPERIMENTAL50 mg QD AMG706 + panitumumab + FOLFIRI
Part 2 AMG 706 (MTD) + FOLFIRI
EXPERIMENTALMaximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI
100 mg QD AMG 706 + FOLFIRI
EXPERIMENTAL100 mg AMG 706 + FOLFIRI
75 mg QD AMG 706 + panitumumab + FOLFOX-4
EXPERIMENTAL75 mg QD AMG 706 + panitumumab + FOLFOX-4
75 mg BID AMG 706 + panitumumab + FOLFIRI
EXPERIMENTAL75 mg BID AMG 706 + panitumumab + FOLFIRI
125 mg QD AMG 706 + panitumumab + FOLFIRI
EXPERIMENTAL125 mg QD AMG 706 + panitumumab + FOLFIRI
125 mg QD AMG 706 + FOLFIRI
EXPERIMENTAL125 mg QD AMG 706 + FOLFIRI
100 mg QD AMG 706 + panitumumab + FOLFIRI
EXPERIMENTAL100 mg QD AMG 706 + panitumumab + FOLFIRI
75 mg QD AMG 706 + FOLFOX-4
EXPERIMENTAL75 mg QD AMG 706 + FOLFOX-4
100 mg QD AMG 706 + FOLFOX-4
EXPERIMENTAL100 mg QD AMG 706 + FOLFOX-4
50 mg QD AMG 706 + panitumumab + FOLFOX-4
EXPERIMENTAL50 mg QD AMG 706 + panitumumab + FOLFOX-4
75 mg QD AMG706 + panitumumab + FOLFIRI
EXPERIMENTAL75 mg QD AMG706 + panitumumab + FOLFIRI
Interventions
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
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.
Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
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.
Eligibility Criteria
You may not qualify if:
- 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
- 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)
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Related Publications (1)
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.
PMID: 25772756DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
MD
Amgen
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 18, 2005
First Posted
January 19, 2005
Study Start
December 1, 2004
Primary Completion
April 1, 2010
Study Completion
December 1, 2011
Last Updated
September 17, 2012
Record last verified: 2012-09