QUILT-2.018: Safety & Efficacy of FOLFIRI With AMG 479 or AMG 655 vs FOLFIRI Alone in KRAS-mutant Metastatic Colorectal Carcinoma

Study Overview
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Brief Summary
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This is a phase 2, multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-arm trial to be conducted in the United States, Europe, and Asia. Approximately 150 eligible KRAS-mutant metastatic colorectal cancer subjects who have failed first line fluoropyrimidine and oxaliplatin-based regimen with or without anti-VEGF therapy will be randomized in a 1:1:1 ratio to receive AMG 479 placebo plus AMG 655 with FOLFIRI, or AMG 479 plus AMG 655 placebo with FOLFIRI, or AMG 479 placebo plus AMG 655 placebo with FOLFIRI

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy of FOLFIRI in Combination With AMG 479 or AMG 655 Versus FOLFIRI for the Second-line Treatment of KRAS-mutant Metastatic Colorectal Carcinoma

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Other: FOLFIRI
* Biological: AMG 655
* Other: Placebo
* Biological: AMG 479


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of colon or rectum in patients with metastatic disease Mutant-type KRAS tumor at screening Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1 Adequate hematology, renal, hepatic, and coagulation function Exclusion Criteria: History or known presence of central nervous system metastases History of other malignancy Prior irinotecan-based chemotherapy for advanced/metastatic disease Prior death receptor agonists, or other systemic IGF-1R agonists in any setting Uncontrolled cardiovascular disease

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>AMG 655 10 mg/kg plus AMG 479 placebo in combination with FOLFIRI every 14 days | Other: FOLFIRI<br>* Day 1 of each Cycle Combination Therapy of: irinotecan 180 mg/m2 90-minute infusion leucovorin 400 mg/m2 2 hour infusion 5-FU 400 mg/m2 IV bolus 5-FU 2,400 mg/m2 46-48 hour infusion<br>Biological: AMG 655<br>* AMG 655 is an investigational, fully human, monoclonal antibody that selectively binds to Death Receptor-5 (DR-5)<br>* Other names: Conatumumab;Other: Placebo<br>* Inactive dummy agent (to maintain blind)<br>|
| Active Comparator: Arm C<br>AMG 479 Placebo plus AMG 655 Placebo in combination with FOLFIRI every 14 days | Other: FOLFIRI<br>* Day 1 of each Cycle Combination Therapy of: irinotecan 180 mg/m2 90-minute infusion leucovorin 400 mg/m2 2 hour infusion 5-FU 400 mg/m2 IV bolus 5-FU 2,400 mg/m2 46-48 hour infusion<br>Other: Placebo<br>* Inactive dummy agent (to maintain blind)<br>|
| Experimental: Arm B<br>AMG 479 12 mg/kg plus AMG 655 placebo in combination with FOLFIRI every 14 days | Other: FOLFIRI<br>* Day 1 of each Cycle Combination Therapy of: irinotecan 180 mg/m2 90-minute infusion leucovorin 400 mg/m2 2 hour infusion 5-FU 400 mg/m2 IV bolus 5-FU 2,400 mg/m2 46-48 hour infusion<br>Other: Placebo<br>* Inactive dummy agent (to maintain blind)<br>Biological: AMG 479<br>* AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1<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 |
| --- | --- | --- |
| Overall Survival, Objective Response, Duration of Response, Time to Response |  | Length of Study | 
| Incidence of adverse events |  | Length of Study | 
| Significant laboratory abnormalities |  | Length of Study | 
| Incidence of 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, Rectal Cancer, Monoclonal Antibody, Clinical Trial, Colorectal Cancer, metastatic colorectal cancer, metastatic cancer, antibody-2nd line, KRAS, adenocarcinoma, AMG 655, AMG 479