A Phase 3 Study of Rilotumumab (AMG 102) With Cisplatin and Capecitabine (CX) as First-line Therapy in Gastric Cancer

Study Overview
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Brief Summary
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This is a Phase 3, multicenter, randomized, double-blind, placebo controlled study of Rilotumumab (AMG 102) with Cisplatin and Capecitabine (CX) for untreated advanced mesenchymal epithelial transition factor (MET)-positive gastric or gastroesophageal junction adenocarcinoma (GEJ).

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled Study of Rilotumumab (AMG 102) With Cisplatin and Capecitabine (CX) as First-line Therapy in Advanced MET-Positive Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Rilotumumab
* Drug: Placebo
* Drug: Cisplatin
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Pathologically confirmed unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Tumor MET-positive by immunohistochemistry (IHC). Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Male or female subject greater than or equal to 20 years of age at the time of informed consent. Key Exclusion Criteria: Human epidermal growth factor receptor 2 (HER2)-overexpressing locally advanced or metastatic gastric or GEJ adenocarcinoma. Previous systemic therapy for locally advanced or metastatic gastric or GEJ or lower esophageal adenocarcinoma. Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy to randomization. Squamous cell histology.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 100 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: Rilotumumab<br>Rilotumumab plus Cisplatin and Capecitabine (CX). | Drug: Rilotumumab<br>* Rilotumumab is a fully human monoclonal antibody immunoglobulin G, type 2 (IgG2) against human hepatocyte growth factor/scatter factor (HGF/SF) that blocks binding of HGF/SF to its receptor MET, inhibiting HGF/SF/MET-driven activities in cells.<br>* Other names: AMG102;Drug: Cisplatin<br>* A platinum containing chemo-therapy compound that reacts in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death)<br>* Other names: Platinal-AQ;Drug: Capecitabine<br>* A chemo-therapy prodrug that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.<br>* Other names: Xeloda;|
| Placebo Comparator: Placebo<br>Rilotumumab-placebo plus Cisplatin and Capecitabine (CX). | Drug: Placebo<br>* Placebo<br>Drug: Cisplatin<br>* A platinum containing chemo-therapy compound that reacts in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death)<br>* Other names: Platinal-AQ;Drug: Capecitabine<br>* A chemo-therapy prodrug that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | To determine if the treatment of rilotumumab in combination with CX significantly improves progression-free survival as compared with rilotumumab-placebo in combination with CX in subjects with unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma with MET-positive expression. | 4 years | 
| Overall Survival | To determine if the treatment of rilotumumab in combination with CX significantly improves overall survival as compared with rilotumumab-placebo in combination with CX in subjects with unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma with MET-positive expression. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP | Time to Progression (TTP) | 4 years | 
| ORR | Objective Response Rate | 4 years | 
| DCR | Disease Control Rate | 4 years | 
| TTR | Time to Response | 4 years | 
| Incidence of subject adverse events, laboratory abnormalities and immunogenicity | Adverse events and laboratory abnormalities are reported by Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, First Line Treatment Gastroesophageal Junction (GEJ), Gastroesophageal Junction Cancer (GEJ), GEJ Cancer