First-Line Treatment for Locally Advanced or Metastatic Mesenchymal Epithelial Transition Factor (MET) - Positive Gastric, Lower Esophageal, or Gastroesophageal Junction (GEJ) Adenocarcinoma (RILOMET-1)

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled Study of Rilotumumab (AMG102) With Epirubicin, Cisplatin, and Capecitabine (ECX) as First-line Therapy in Advanced MET-Positive Gastric or Gastroesophageal Junction Adenocarcinoma

This is a phase 3, multicenter, randomized, double-blind, placebo controlled study of epirubicin, cisplatin & capecitabine (ECX) with rilotumumab or placebo for untreated advanced MET-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma

Study Overview

• Status: Terminated
• Conditions: Gastric Cancer
• Intervention / Treatment: Other: Placebo; Drug: Rilotumumab; Drug: Epirubicin; Drug: Cisplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Research Site
    • St Leonards, New South Wales, Australia, 2065
      • Research Site
    • Tweed Heads, New South Wales, Australia, 2485
      • Research Site
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Research Site
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Research Site
    • Kurralta Park, South Australia, Australia, 5037
      • Research Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Research Site
    • Ringwood East, Victoria, Australia, 3135
      • Research Site
• Austria
  • Graz, Austria, 8036
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Linz, Austria, 4010
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
  • Wien, Austria, 1090
    • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Bruxelles, Belgium, 1180
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• Brazil
  • São Paulo, Brazil, 01246-000
    • Research Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-321
      • Research Site
  • Rio Grande do Sul
    • Pelotas, Rio Grande do Sul, Brazil, 96015-280
      • Research Site
  • São Paulo
    • Santo Andre, São Paulo, Brazil, 09060-650
      • Research Site
    • Sao Paulo, São Paulo, Brazil, 01509-900
      • Research Site
    • Sao Paulo, São Paulo, Brazil, 01209-000
      • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Shumen, Bulgaria, 9700
    • Research Site
  • Sofia, Bulgaria, 1527
    • Research Site
  • Sofia, Bulgaria, 1233
    • Research Site
  • Sofia, Bulgaria, 1756
    • Research Site
  • Sofia, Bulgaria, 1606
    • Research Site
  • Varna, Bulgaria, 9010
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Research Site
    • Toronto, Ontario, Canada, M4C 3E7
      • Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Research Site
    • Laval, Quebec, Canada, H7M 3L9
      • Research Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Research Site
• Czech Republic
  • Horovice, Czech Republic, 268 31
    • Research Site
  • Hradec Kralove, Czech Republic, 500 05
    • Research Site
  • Olomouc, Czech Republic, 775 20
    • Research Site
  • Praha 2, Czech Republic, 120 00
    • Research Site
  • Usti nad Labem, Czech Republic, 401 13
    • Research Site
• Denmark
  • Aalborg, Denmark, 9000
    • Research Site
  • Copenhagen, Denmark, 2100
    • Research Site
  • Odense, Denmark, 5000
    • Research Site
  • Århus C, Denmark, 8000
    • Research Site
• France
  • Bayonne, France, 64109
    • Research Site
  • Bordeaux, France, 33075
    • Research Site
  • Clermont Ferrand Cedex 1, France, 63003
    • Research Site
  • Dijon cedex, France, 21079
    • Research Site
  • Le Mans, France, 72000
    • Research Site
  • Limoges Cedex, France, 87042
    • Research Site
  • Lyon Cedex 03, France, 69437
    • Research Site
  • Lyon Cedex 08, France, 69373
    • Research Site
  • Marseille cedex 5, France, 13385
    • Research Site
  • Montpellier Cedex 5, France, 34298
    • Research Site
  • Nice cedex 2, France, 06189
    • Research Site
  • Périgueux cedex, France, 24004
    • Research Site
  • Saint Priest en Jarez, France, 42270
    • Research Site
  • Saint Priest en Jarez Cedex, France, 42270
    • Research Site
  • Strasbourg, France, 67000
    • Research Site
• Germany
  • Berlin, Germany, 13125
    • Research Site
  • Bielefeld, Germany, 33611
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Essen, Germany, 45276
    • Research Site
  • Frankfurt am Main, Germany, 60488
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Magdeburg, Germany, 39104
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • München, Germany, 81377
    • Research Site
  • München, Germany, 81737
    • Research Site
  • Oldenburg, Germany, 26133
    • Research Site
  • Schweinfurt, Germany, 97422
    • Research Site
• Greece
  • Athens, Greece, 18547
    • Research Site
  • Heraklion - Crete, Greece, 71110
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Nea Kifissia, Athens, Greece, 14564
    • Research Site
  • Patra, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 56429
    • Research Site
  • Thessaloniki, Greece, 54645
    • Research Site
• Hungary
  • Budapest, Hungary, 1106
    • Research Site
  • Budapest, Hungary, 1097
    • Research Site
  • Gyor, Hungary, 9023
    • Research Site
  • Nyiregyhaza, Hungary, 4400
    • Research Site
  • Szeged, Hungary, 6725
    • Research Site
  • Szolnok, Hungary, 5000
    • Research Site
• Italy
  • Aviano PN, Italy, 33081
    • Research Site
  • Brescia, Italy, 25124
    • Research Site
  • Catania, Italy, 95122
    • Research Site
  • Firenze, Italy, 50134
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Pisa, Italy, 56126
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• Mexico
  • Distrito Federal, Mexico, 04380
    • Research Site
  • Toluca, Mexico, 50080
    • Research Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14000
      • Research Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
      • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Elblag, Poland, 82-300
    • Research Site
  • Gdansk, Poland, 80-219
    • Research Site
  • Konin, Poland, 62-500
    • Research Site
  • Lodz, Poland, 93-513
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Portugal
  • Aveiro, Portugal, 3814-501
    • Research Site
  • Guimaraes, Portugal, 4835-044
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
  • Santa Maria da Feira, Portugal, 4520-211
    • Research Site
  • Vila Real, Portugal, 5000-508
    • Research Site
• Romania
  • Alba Iulia, Romania, 510077
    • Research Site
  • Baia Mare, Romania, 430241
    • Research Site
  • Brasov, Romania, 500091
    • Research Site
  • Bucharest, Romania, 022328
    • Research Site
  • Bucharest, Romania, 011461
    • Research Site
  • Bucharest, Romania, 010719
    • Research Site
  • Cluj Napoca, Romania, 400015
    • Research Site
  • Cluj-Napoca, Romania, 400015
    • Research Site
  • Cluj-Napoca, Romania, 400058
    • Research Site
  • Lasi, Romania, 700106
    • Research Site
  • Timisoara, Romania, 300167
    • Research Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Research Site
  • Ivanovo, Russian Federation, 153013
    • Research Site
  • Kazan, Russian Federation, 420029
    • Research Site
  • Krasnodar, Russian Federation, 350040
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Saint-Petersburg, Russian Federation, 197758
    • Research Site
  • Samara, Russian Federation, 443031
    • Research Site
  • Vladimir, Russian Federation, 600020
    • Research Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Research Site
  • Bratislava, Slovakia, 833 10
    • Research Site
  • Poprad, Slovakia, 058 01
    • Research Site
  • Trencin, Slovakia, 911 71
    • Research Site
• South Africa
  • Cape Town, South Africa, 7925
    • Research Site
  • Johannesburg, South Africa, 2193
    • Research Site
  • Kraaifontein, South Africa, 7570
    • Research Site
  • Pretoria, South Africa, 0002
    • Research Site
  • Gauteng
    • Groenkloof, Gauteng, South Africa, 0181
      • Research Site
• Spain
  • Madrid, Spain, 28050
    • Research Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Research Site
    • Terrassa, Cataluña, Spain, 08221
      • Research Site
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Research Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Research Site
• Sweden
  • Eskilstuna, Sweden, 631 88
    • Research Site
  • Stockholm, Sweden, 171 76
    • Research Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Research Site
  • Bern, Switzerland, 3010
    • Research Site
  • Chur, Switzerland, 7000
    • Research Site
• Turkey
  • Ankara, Turkey, 06100
    • Research Site
  • Gaziantep, Turkey, 27100
    • Research Site
  • Istanbul, Turkey, 34390
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Research Site
  • Kharkiv, Ukraine, 61070
    • Research Site
  • Kherson, Ukraine, 73035
    • Research Site
  • Kyiv, Ukraine, 03115
    • Research Site
  • Lutsk, Ukraine, 43018
    • Research Site
  • Lviv, Ukraine, 79031
    • Research Site
  • Mariupol, Ukraine, 87500
    • Research Site
  • Sumy, Ukraine, 40022
    • Research Site
  • Uzhgorod, Ukraine, 88000
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Research Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Research Site
  • Guildford, United Kingdom, GU2 7XX
    • Research Site
  • Leicester, United Kingdom, LE1 5WW
    • Research Site
  • London, United Kingdom, SW3 6JJ
    • Research Site
  • London, United Kingdom, SE1 9RT
    • Research Site
  • London, United Kingdom, NW1 2PQ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Research Site
  • Northwood, United Kingdom, HA6 2RN
    • Research Site
  • Salisbury, United Kingdom, SP2 8BJ
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
    • Pueblo, Colorado, United States, 81008
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Research Site
  • Minnesota
    • Woodbury, Minnesota, United States, 55125
      • Research Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Research Site
    • Winston Salem, North Carolina, United States, 27103
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Texas
    • Bedford, Texas, United States, 76022
      • Research Site
    • Dallas, Texas, United States, 75246
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)
• Evaluable (measurable or non-measurable) disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria

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 adenocarcinoma
• Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy to randomization
• Previous treatment with anthracyclines must not exceed total cumulative dose of epirubicin of 400 mg/m2
• Squamous cell histology
• Left ventricular ejection fraction (LVEF) < 50%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rilotumumab; Rilotumumab (15 mg/kg, IV every 21 days) plus Epirubicin, Cisplatin and Capecitabine (ECX)	Drug: Rilotumumab; 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/MET-driven activities in cells.; Other Names: AMG102; Drug: Epirubicin; Epirubicin is an anthracycline cytotoxic agent.; Other Names: Ellence; Pharmorubicin PFS; Pharmorubicin RDF; Drug: Cisplatin; Cisplatin is a non-cell cycle specific chemotherapeutic agent.; Other Names: Platinol; Platinol-AQ; Drug: Capecitabine; Capecitabine is an oral fluoropyrimidine.; Other Names: Xeloda
Placebo Comparator: Placebo; Rilotumumab-placebo (15 mg/kg, IV every 21 days) plus Epirubicin, Cisplatin and Capecitabine (ECX)	Other: Placebo; Placebo; Other Names: sterile protein-free solution; Drug: Epirubicin; Epirubicin is an anthracycline cytotoxic agent.; Other Names: Ellence; Pharmorubicin PFS; Pharmorubicin RDF; Drug: Cisplatin; Cisplatin is a non-cell cycle specific chemotherapeutic agent.; Other Names: Platinol; Platinol-AQ; Drug: Capecitabine; Capecitabine is an oral fluoropyrimidine.; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To determine if the treatment of rilotumumab in combination with ECX significantly improves overall survival in subjects with unresectable locally advanced or metastatic MET positive gastric or GEJ cancer	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety		3 years
PFS	Progression Free Survival (PFS)	3 years
TTP	Time to Progression (TTP)	3 years
ORR	Objective Response Rate (ORR)	3 years
DCR	Disease Control Rate (DCR)	3 years
TTR	Time to Response (TTR)	3 years
Immunogenicity		3 years

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. doi: 10.1016/S1470-2045(17)30566-1. Epub 2017 Sep 25.
• Doshi S, Gisleskog PO, Zhang Y, Zhu M, Oliner KS, Loh E, Perez Ruixo JJ. Rilotumumab exposure-response relationship in patients with advanced or metastatic gastric cancer. Clin Cancer Res. 2015 Jun 1;21(11):2453-61. doi: 10.1158/1078-0432.CCR-14-1661. Epub 2015 Feb 24.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: September 28, 2012
• First Posted (Estimate): October 2, 2012

Study Record Updates

• Last Update Posted (Estimate): February 9, 2016
• Last Update Submitted That Met QC Criteria: January 18, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Gastric Cancer; GEJ Cancer; First Line Treatment Gastroesophageal Junction (GEJ); Gastroesophageal Junction Cancer (GEJ)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cisplatin; Capecitabine; Epirubicin; Rilotumumab
• Other Study ID Numbers: 20070622; 2011-004923-11 (EudraCT Number)