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

NCT ID: NCT00101894

Last Updated: 2012-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

119 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-12-31

Study Completion Date

2011-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Rectal Cancer Colon Cancer

Keywords

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AMG 706 Panitumumab

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 2 AMG 706 (MTD) + FOLFOX-4

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

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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

125 mg QD AMG 706 + FOLFOX-4

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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

50 mg QD AMG706 + panitumumab + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

FOLFIRI

Intervention Type DRUG

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.

Part 2 AMG 706 (MTD) + FOLFIRI

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

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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.

FOLFIRI

Intervention Type DRUG

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.

100 mg QD AMG 706 + FOLFIRI

100 mg AMG 706 + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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.

FOLFIRI

Intervention Type DRUG

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.

75 mg QD AMG 706 + panitumumab + FOLFOX-4

75 mg QD AMG 706 + panitumumab + FOLFOX-4

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

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

75 mg BID AMG 706 + panitumumab + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

FOLFIRI

Intervention Type DRUG

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.

125 mg QD AMG 706 + panitumumab + FOLFIRI

125 mg QD AMG 706 + panitumumab + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

FOLFIRI

Intervention Type DRUG

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.

125 mg QD AMG 706 + FOLFIRI

125 mg QD AMG 706 + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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.

FOLFIRI

Intervention Type DRUG

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.

100 mg QD AMG 706 + panitumumab + FOLFIRI

100 mg QD AMG 706 + panitumumab + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

FOLFIRI

Intervention Type DRUG

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.

75 mg QD AMG 706 + FOLFOX-4

75 mg QD AMG 706 + FOLFOX-4

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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

100 mg QD AMG 706 + FOLFOX-4

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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 AMG 706 + panitumumab + FOLFOX-4

50 mg QD AMG 706 + panitumumab + FOLFOX-4

Group Type EXPERIMENTAL

FOLFOX-4

Intervention Type DRUG

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

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

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

75 mg QD AMG706 + panitumumab + FOLFIRI

Group Type EXPERIMENTAL

AMG 706

Intervention Type DRUG

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 (Part 1a only)

Intervention Type BIOLOGICAL

Panitumumab will be administered by IV infusion at a dose of 6 mg/kg on day 1 of each 2-week cycle.

FOLFIRI

Intervention Type DRUG

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.

Interventions

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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

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type BIOLOGICAL

FOLFIRI

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form
2. Diagnosis of metastatic colorectal adenocarcinoma (may have received 1 prior chemotherapy regimen for metastatic CRC)
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Adequate hematological function
5. Adequate renal function
6. Adequate hepatic function
7. Life expectancy of greater than or equal to 3 months as documented by the investigator

Exclusion Criteria

1. More than 1 prior chemotherapy regimen for metastatic CRC
2. Central nervous system (CNS) metastases
3. History of venous thrombosis
4. 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
5. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on screening chest computed tomograph (CT) scan
6. Average systolic blood pressure \> 150mm Hg or average diastolic blood pressure of \> 90mm Hg
7. Radiotherapy within 28 days of study enrollment or within 14 days of study enrollment for peripheral lesions
8. Prior AMG 706, oral inhibitors of AMG706, panitumumab, or another anti-EGFr monoclonal antibody (mAb) (e.g., cetuximab \[Erbitux®\] or EMD 72000)
9. Systemic chemotherapy within 28 days before study enrollment
10. Major surgery within 28 days or minor surgery within 7days of study enrollment
11. History of life threatening ventricular arrhythmia (eg, sustained ventricular tachycardia)
12. Female and male subjects of childbearing potential not using adequate contraceptive precautions
13. Participation in therapeutic clinical trials within 30 days before study enrollment
14. Not recovered from all previous therapies
15. Clinically significant open would, ulcer or fracture
16. Any co-morbid medical condition that would increase the risk of toxicity
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Countries

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Australia United States

References

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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.

Reference Type DERIVED
PMID: 25772756 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20040205

Identifier Type: -

Identifier Source: org_study_id

NCT00107328

Identifier Type: -

Identifier Source: nct_alias