QUILT-2.019: A Study of AMG 655 or AMG 479 in Combination With Gemcitabine for Treatment of Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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This is a multi-center, 2-part study of AMG 655, AMG 479 or AMG 655-placebo plus gemcitabine as first-line treatment of subjects with metastatic pancreatic cancer. Part 1 is an open-label, dose-escalation phase 1b segment to determine the safety, tolerability and maximum tolerated dose of AMG 655 in combination with gemcitabine. Enrollment into part 1 of the study has been completed. Part 2 is a randomized, placebo-controlled phase 2 segment to estimate the efficacy as assessed by 6 month survival of AMG 655, AMG 479, or AMG 655-placebo in combination with gemcitabine. The phase 2 segment that will commence after dose selection in part 1. In part 2, subjects will be randomized 1:1:1 to AMG 655, AMG 479, or placebo in combination with gemcitabine.

Official Title
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A Phase 1b/2 Study to Evaluate the Safety and Efficacy of AMG 655 or AMG 479 in Combination With Gemcitabine as First-Line Therapy for Metastatic Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Metastatic Pancreatic Cancer, Pancreatic Cancer

Intervention / Treatment
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* Other: Placebo
* Drug: AMG 479
* Drug: AMG 655


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated metastatic adenocarcinoma of the pancreas (AJCC Stage IV) Subjects with unresectable pancreatic cancer who have had surgery are eligible if fully recovered and greater than 30 days have elapsed since the surgery. Subjects with a history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence. Men or women ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Adequate hematologic, hepatic, renal and coagulation function Amylase and lipase ≤ 2.0 x ULN Adequately controlled type 1 or 2 diabetic subjects Exclusion Criteria: Islet cell, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma, etc), adenocarcinoma originated from biliary tree or cystadenocarcinoma Known central nervous system metastases Uncontrolled cardiac disease or any other co-morbid disease that would increase the risk of toxicity Adjuvant chemotherapy or chemoradiotherapy

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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Gemcitabine<br> | Other: Placebo<br>* Inactive dummy of AMG 655.<br>|
| Experimental: AMG 655 + Gemcitabine<br> | Drug: AMG 655<br>* AMG 655 is a fully human monoclonal agonist antibody directed against TRAIL Receptor 2 (TR-2).<br>|
| Experimental: AMG 479 + Gemcitabine<br> | Drug: AMG 479<br>* AMG 479 is fully human monoclonal antagonist antibody targeted against insulin-like growth factor receptor type 1 (IGF-1R).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 6 months | 
| Safety |  | Length of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Efficacy Endpoints |  | Length of the study | 
| Overall Survival |  | Length of the study | 
| Time to Response |  | Length of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 479, Gemcitabine, TR-2, IGF-1R, AMG 655, Pancreatic cancer, Adenocarcinoma of the Pancreas, Metastatic Pancreatic Cancer