Ganitumab in Locally Advanced Unresectable Adenocarcinoma of the Pancreas

Study Overview
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Brief Summary
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This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1). Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

Detailed Description
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This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1). Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of AMG 479 or Placebo in Combination With Gemcitabine as First-line Therapy for Locally Advanced Unresectable Adenocarcinoma of the Pancreas

Conditions
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Adenocarcinoma of the Pancreas, Locally Advanced, Unresectable

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: AMG 479
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is unresectable, per institutional practice Radiologically measurable and/or non-measurable disease as defined by RECIST version 1.1 Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 Men or women >/= 18 years of age Adequate organ function Exclusion Criteria: Early (stage I) or metastatic (stage IV) disease Islet cell, acinar cell carcinoma, non-adenocarcinoma, (eg, lymphoma, sarcoma, etc), adenocarcinoma originating from biliary tree or cystadenocarcinoma External biliary drain Currently treated or previously treated with biologic, small molecule, immunotherapy, chemotherapy (ie, including gemcitabine), or other agents for pancreatic cancer Currently treated or previously treated with radiotherapy, or chemoradiotherapy for pancreatic cancer

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 |
| --- | --- |
| Active Comparator: Placebo + Gemcitabine<br>Arm 2: AMG479-placebo IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle | Drug: Gemcitabine<br>* Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.<br>* Other names: Gemzar;Drug: Placebo<br>* Gemcitabine on Days 1, 8, and 15 followed by Placebo 20 mg/kg on days 1 and 15 of every 28 day cycle<br>|
| Experimental: AMG 479 20 mg/kg + Gemcitabine<br>ARM 1: AMG 479 20mg/kg IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle. | Drug: Gemcitabine<br>* Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.<br>* Other names: Gemzar;Drug: AMG 479<br>* Gemcitabine on days 1, 8, and 15, followed by AMG 479 20 mg/kg on days 1 and 15 of every 28 day cycle.<br>* Other names: gemcitabine = Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is progression-free survival (PFS) as defined as the time from randomization to progression (per RECIST v1.1) or death. |  | Approximately 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival and overall survival rates at 3, 6, 9, 12, 18, and 24 months |  | Approximately 23 months | 
| Objective response rate (complete or partial response) per RECIST v1.1 |  | Approximately 23 months | 
| Overall survival |  | Approximately 23 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma, pancreas, pancreatic cancer, local, unresectable, stage II, stage III