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

Amgen

Status and phase: Completed; Phase 1

Conditions: Colon Cancer; Rectal Cancer

Treatments: Drug: FOLFOX-4; Drug: FOLFIRI; Biological: Panitumumab (Part 1a only); Drug: AMG 706

Study type: Interventional

Funder types: Industry

Identifiers

NCT00101894

20040205

Details and patient eligibility

About

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.

Enrollment: 119 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For complete inclusion and exclusion criteria, please refer to the investigator. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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119 participants in 14 patient groups

Part 2 AMG 706 (MTD) + FOLFOX-4

Experimental group

Description:

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

Treatment:

Drug: AMG 706

Drug: FOLFOX-4

125 mg QD AMG 706 + FOLFOX-4

Experimental group

Description:

125 mg QD AMG 706 + FOLFOX-4

Treatment:

Drug: AMG 706

Drug: FOLFOX-4

50 mg QD AMG706 + panitumumab + FOLFIRI

Experimental group

Description:

50 mg QD AMG706 + panitumumab + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

Biological: Panitumumab (Part 1a only)

Part 2 AMG 706 (MTD) + FOLFIRI

Experimental group

Description:

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

Treatment:

Drug: AMG 706

Drug: FOLFIRI

100 mg QD AMG 706 + FOLFIRI

Experimental group

Description:

100 mg AMG 706 + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

75 mg QD AMG 706 + panitumumab + FOLFOX-4

Experimental group

Description:

75 mg QD AMG 706 + panitumumab + FOLFOX-4

Treatment:

Drug: AMG 706

Biological: Panitumumab (Part 1a only)

Drug: FOLFOX-4

75 mg BID AMG 706 + panitumumab + FOLFIRI

Experimental group

Description:

75 mg BID AMG 706 + panitumumab + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

Biological: Panitumumab (Part 1a only)

125 mg QD AMG 706 + panitumumab + FOLFIRI

Experimental group

Description:

125 mg QD AMG 706 + panitumumab + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

Biological: Panitumumab (Part 1a only)

125 mg QD AMG 706 + FOLFIRI

Experimental group

Description:

125 mg QD AMG 706 + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

100 mg QD AMG 706 + panitumumab + FOLFIRI

Experimental group

Description:

100 mg QD AMG 706 + panitumumab + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

Biological: Panitumumab (Part 1a only)

75 mg QD AMG 706 + FOLFOX-4

Experimental group

Description:

75 mg QD AMG 706 + FOLFOX-4

Treatment:

Drug: AMG 706

Drug: FOLFOX-4

100 mg QD AMG 706 + FOLFOX-4

Experimental group

Description:

100 mg QD AMG 706 + FOLFOX-4

Treatment:

Drug: AMG 706

Drug: FOLFOX-4

50 mg QD AMG 706 + panitumumab + FOLFOX-4

Experimental group

Description:

50 mg QD AMG 706 + panitumumab + FOLFOX-4

Treatment:

Drug: AMG 706

Biological: Panitumumab (Part 1a only)

Drug: FOLFOX-4

75 mg QD AMG706 + panitumumab + FOLFIRI

Experimental group

Description:

75 mg QD AMG706 + panitumumab + FOLFIRI

Treatment:

Drug: AMG 706

Drug: FOLFIRI

Biological: Panitumumab (Part 1a only)