Phase 1b/2 Study of AMG 655 With mFOLFOX6 and Bevacizumab for First-Line Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This phase 1/2, multi-center, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of AMG 655 when combined with mFOLFOX6 and bevacizumab compared with mFOLFOX6 and bevacizumab alone in subjects with previously untreated metastatic colorectal cancer (CRC). The clinical benefit of AMG 655 in combination with mFOLFOX6 and bevacizumab will be measured by progression-free survival, objective response rate, time to response, duration of response, and overall survival. This study is also designed to evaluate the safety and tolerability of AMG 655 in combination with mFOLFOX6 and bevacizumab and to evaluate anti-AMG 655 antibody formation and the pharmacokinetics of AMG 655.

Official Title
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A Phase 1b/2 Study of AMG 655 in Combination With Modified FOLFOX6 and Bevacizumab for the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer, Colon Cancer, Colorectal Cancer, Rectal Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: AMG 655
* Drug: Modified FOLFOX6
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. Subjects with measurable or unmeasurable disease Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Men or women at least 18 years of age Adequate hematologic, renal, hepatic and coagulation function Exclusion Criteria: History or known presence of central nervous system (CNS) metastases Prior chemotherapy or other systemic therapy for advanced or metastatic CRC Any investigational agent or therapy for advanced or metastatic CRC Clinically significant cardiac disease Clinically significant peripheral neuropathy Active inflammatory bowel disease Recent gastrointestinal ulcer or hemorrhage Recent arterial thrombotic event or pulmonary embolus Recent history of clinically significant bleeding, bleeding diathesis, or coagulopathy Recent major surgical procedure or not yet recovered from major surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 655 Low Dose<br>AMG 655 (low dose) + mFOLFOX6 + Bevacizumab | Drug: AMG 655<br>* AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).<br>Drug: Modified FOLFOX6<br>* Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)<br>* Other names: mFOLFOX6;Drug: Bevacizumab<br>* Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).<br>|
| Placebo Comparator: Placebo<br>Placebo + mFOLFOX6 + Bevacizumab | Drug: Placebo<br>* Inactive dummy AMG 655 (to maintain blind)<br>Drug: Modified FOLFOX6<br>* Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)<br>* Other names: mFOLFOX6;Drug: Bevacizumab<br>* Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).<br>|
| Experimental: AMG 655 High Dose<br>AMG 655 (high dose) + mFOLFOX6 + Bevacizumab | Drug: AMG 655<br>* AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).<br>Drug: Modified FOLFOX6<br>* Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)<br>* Other names: mFOLFOX6;Drug: Bevacizumab<br>* Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | Length of study | 
| Duration of response |  | Length of study | 
| Time-to-response |  | Length of study | 
| Overall survival |  | Length of study | 
| AMG 655 pharmacokinetic parameters |  | Length of study | 
| The incidence of anti-AMG 655 antibody formation |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colon Cancer, Colorectal Cancer, Rectal Cancer, AMG 655, Bevacizumab, Modified FOLFOX6, mFOLFOX6, FOLFOX