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

• ClinicalTrials.gov Identifier: NCT01697072
• Recruitment Status: Terminated
• First Posted: October 2, 2012
• Last Update Posted: February 9, 2016
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: September 26, 2012
• First Posted Date: October 2, 2012
• Last Update Posted Date: February 9, 2016
• Study Start Date: October 2012
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 28, 2012)

Overall Survival [ Time Frame: 3 years ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 28, 2012)

• PFS [ Time Frame: 3 years ]
  Progression Free Survival (PFS)
• TTP [ Time Frame: 3 years ]
  Time to Progression (TTP)
• ORR [ Time Frame: 3 years ]
  Objective Response Rate (ORR)
• DCR [ Time Frame: 3 years ]
  Disease Control Rate (DCR)
• TTR [ Time Frame: 3 years ]
  Time to Response (TTR)
• Safety [ Time Frame: 3 years ]
• Immunogenicity [ Time Frame: 3 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-Line Treatment for Locally Advanced or Metastatic Mesenchymal Epithelial Transition Factor (MET) - Positive Gastric, Lower Esophageal, or Gastroesophageal Junction (GEJ) Adenocarcinoma
• Official Title: 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
• Brief Summary: 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• 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 Name: AMG102
• Other: Placebo
  Placebo
  Other Name: 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 Name: Xeloda

Study Arms

• Experimental: Rilotumumab
  Rilotumumab (15 mg/kg, IV every 21 days) plus Epirubicin, Cisplatin and Capecitabine (ECX)
  Interventions:

  • Drug: Rilotumumab
  • Drug: Epirubicin
  • Drug: Cisplatin
  • Drug: Capecitabine
• Placebo Comparator: Placebo
  Rilotumumab-placebo (15 mg/kg, IV every 21 days) plus Epirubicin, Cisplatin and Capecitabine (ECX)
  Interventions:

  • Other: Placebo
  • Drug: Epirubicin
  • Drug: Cisplatin
  • Drug: Capecitabine

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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 20, 2015): 609
• Original Estimated Enrollment (submitted: September 28, 2012): 450
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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%

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Mexico, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT01697072
• Other Study ID Numbers: 20070622; 2011-004923-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: January 2016