Safety of AMG 706 Plus Panitumumab Plus Chemotherapy in the Treatment of Subjects With Metastatic Colorectal Cancer - Full Text View

Sponsored by:	Amgen
Information provided by:	Amgen
ClinicalTrials.gov Identifier:	NCT00101894

Purpose

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.

Condition	Intervention	Phase
Colon Cancer Rectal Cancer	Drug: FOLFIRI Drug: FOLFOX-4 Drug: AMG 706 Biological: Panitumumab (Part 1a only)	Phase I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Irinotecan Irinotecan hydrochloride Fluorouracil Oxaliplatin Motesanib Panitumumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety Study
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

Further study details as provided by Amgen:

Primary Outcome Measures:

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) ] [ Designated as safety issue: No ]
Part 1a - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities [ Time Frame: First 2 cycles ] [ Designated as safety issue: Yes ]
Part 1b - The incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxici [ Time Frame: First 2 cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Part 2 - Incidence of subjects undergoing resection of metastases for curative intent [ Time Frame: As needed ] [ Designated as safety issue: Yes ]
Part 2 - The incidence of adverse events and clinical laboratory abnormalities [ Time Frame: Every visit ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Part 1a - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities [ Time Frame: Every visit ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
Part 1a - The incidence of HAPA response following panitumumab administration [ Time Frame: Cycle 1 (Day 1), Cycle 4 (Day 1), End of Study ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
Part 1a - The objective tumor response rate (complete and partial response) throughout the study [ Time Frame: Every 6 to 8 weeks ] [ Designated as safety issue: No ]
Part 1b - The incidence of adverse events and clinical laboratory abnormalities not defined as dose-limiting toxicities [ Time Frame: Every visit ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
Part 1b - The objective tumor response rate (complete and partial response) throughout the study [ Time Frame: Every 8 weeks (+/- 7 days) ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
Part 2 - Time-to-progression [ Time Frame: Time from first dose of investigational product to objective disease progression or death due to disease progression. ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]

Estimated Enrollment:	148
Study Start Date:	December 2004
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Part 2 AMG 706 (MTD) + FOLFOX-4: Experimental Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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.
125 mg QD AMG 706 + FOLFOX-4: Experimental 125 mg QD AMG 706 + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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.
50 mg QD AMG706 + panitumumab + FOLFIRI: Experimental 50 mg QD AMG706 + panitumumab + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
100 mg QD AMG 706 + FOLFIRI: Experimental 100 mg AMG 706 + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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.
Part 2 AMG 706 (MTD) + FOLFIRI: Experimental Maximum Tolerated Dose of AMG 706 established in Part 1b + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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.
75 mg QD AMG 706 + panitumumab + FOLFOX-4: Experimental 75 mg QD AMG 706 + panitumumab + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
75 mg BID AMG 706 + panitumumab + FOLFIRI: Experimental 75 mg BID AMG 706 + panitumumab + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
125 mg QD AMG 706 + panitumumab + FOLFIRI: Experimental 125 mg QD AMG 706 + panitumumab + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
125 mg QD AMG 706 + FOLFIRI: Experimental 125 mg QD AMG 706 + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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.
100 mg QD AMG 706 + panitumumab + FOLFIRI: Experimental 100 mg QD AMG 706 + panitumumab + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
50 mg QD AMG 706 + panitumumab + FOLFOX-4: Experimental 50 mg QD AMG 706 + panitumumab + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
75 mg QD AMG706 + panitumumab + FOLFIRI: Experimental 75 mg QD AMG706 + panitumumab + FOLFIRI	Drug: FOLFIRI Irinotecan will be administered over 90 minutes ± 15 minutes on day 1 of each 2-weekcycle. 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. Drug: AMG 706 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. Biological: Panitumumab (Part 1a only) Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.
75 mg QD AMG 706 + FOLFOX-4: Experimental 75 mg QD AMG 706 + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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.
100 mg QD AMG 706 + FOLFOX-4: Experimental 100 mg QD AMG 706 + FOLFOX-4	Drug: FOLFOX-4 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 Drug: AMG 706 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.

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

United States, Alabama
Research Site	Completed
Mobile, Alabama, United States
United States, California
Research Site	Completed
Los Angelas, California, United States
United States, Maryland
Research Site	Completed
Bethesda, Maryland, United States
United States, North Carolina
Research Site	Completed
Monroe, North Carolina, United States
Research Site	Recruiting
Durham, North Carolina, United States
United States, Pennsylvania
Research Site	Recruiting
Philadelphia, Pennsylvania, United States
United States, South Carolina
Research Site	Recruiting
Greenville, South Carolina, United States
United States, Tennessee
Research Site	Recruiting
Nashville, Tennessee, United States
Research Site	Recruiting
Memphis, Tennessee, United States
Australia
Research Site	Recruiting
Heidelberg, Australia
Australia, New South Wales
Research Site	Recruiting
Randwick, New South Wales, Australia
Australia, South Australia
Research Site	Recruiting
Ashford, South Australia, Australia

Responsible Party:	Amgen Inc. ( Global Development Leader )
Study ID Numbers:	20040205
Study First Received:	January 18, 2005
Last Updated:	December 4, 2008
ClinicalTrials.gov Identifier:	NCT00101894
Health Authority:	United States: Food and Drug Administration