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A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01662869
First received: August 8, 2012
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
This randomized, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with 5-fluorouracil, folinic Acid, and oxaliplatin (mFOLFOX6) in participants with metastatic human epidermal growth receptor (HER) 2-negative and MET-positive adenocarcinoma of the stomach or gastroesophageal junction. Participants will be randomized in a 1:1 ratio to receive either onartuzumab or placebo in combination with mFOLFOX6. Participants may continue to receive onartuzumab or placebo until disease progression, unacceptable toxicity, participant or physician decision to discontinue treatment.

Condition Intervention Phase
Gastric Cancer
Drug: 5-Fluoruracil
Drug: Folinic acid
Drug: Onartuzumab
Drug: Oxaliplatin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Phase III, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab (MetMAb) in Combination With 5-Fluorouracil, Folinic Acid, and Oxaliplatin (mFOLFOX6) in Patients With Metastatic HER2-Negative, MET-Positive Gastroesophageal Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup [ Time Frame: Baseline until death (up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • OS in the Intent-To-Treat (ITT) Population [ Time Frame: Baseline until death (up to approximately 38 months overall) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of Response, as Assessed by Investigator Using RECIST v1.1 [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • Percentage of Participants with a Tumor Response of CR or PR or Stable Disease (SD, Maintained for At Least 6 Months) as Determined by the Investigator Using RECIST v1.1 [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 38 months ] [ Designated as safety issue: No ]
  • Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) of Onartuzumab [ Time Frame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1 and 4, (cycle length = 14 days), at study drug discontinuation visit (up to 38 months) ] [ Designated as safety issue: Yes ]
  • Change from Baseline in ATAs Level of Onartuzumab [ Time Frame: Baseline (pre-dose [within 1 hour before infusion start] on Cycle 1 Day 1), pre-dose on Cycle 4 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months) ] [ Designated as safety issue: No ]
  • Minimum Serum Concentration of Onartuzumab (Cmin) [ Time Frame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 2 and 4, 30 minutes after end of infusion (duration of infusion = 60 minutes) on Cycle 1 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months) ] [ Designated as safety issue: No ]
  • Maximum Serum Concentration (Cmax) of Onartuzumab [ Time Frame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 2 and 4, 30 minutes after end of infusion (duration of infusion = 60 minutes) on Cycle 1 Day 1 (cycle length = 14 days), at study drug discontinuation visit (up to 38 months) ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in MET IHC 2+/3+ Participant Subgroup [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • PFS, as Assessed by Investigator Using RECIST v1.1 in ITT Population [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • Percentage of Participants with a Tumor Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator Using RECIST v1.1 in MET IHC 2+/3+ Participant Subgroup [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • Percentage of Participants with a Tumor Response of CR or PR as Determined by the Investigator Using RECIST v1.1 in ITT Population [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 6 weeks for 12 months and thereafter every 12 weeks up to approximately 38 months overall) ] [ Designated as safety issue: No ]
  • European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (EORTC QLQ-C30) Score [ Time Frame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months ] [ Designated as safety issue: No ]
  • EORTC QLQ-Gastric cancer Specific Quality of Life Questionnaire (EORTC QLQ-STOC22) Score [ Time Frame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months ] [ Designated as safety issue: No ]
  • European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Score [ Time Frame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months ] [ Designated as safety issue: No ]

Enrollment: 564
Study Start Date: November 2012
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Onartuzumab+mFOLFOX6
Participants will receive onartuzumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion + mFOLFOX6 (oxaliplatin, folinic acid, and 5-fluoruracil) regimen. Participants will receive a maximum of 12 cycles (each cycle is 14 days) of mFOLFOX6 with onartuzumab. Participants whose disease has not progressed after 12 cycles of mFOLFOX6 with onartuzumab will continue treatment with onartuzumab until disease progression, unacceptable toxicity, or death.
Drug: 5-Fluoruracil
Participants will receive 5-fluorouracil 400 milligrams per square meter (mg/m^2) IV bolus and then 2400 mg/m^2 as a continuous IV infusion over 46-48 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Drug: Folinic acid
Participants will receive folinic acid 400 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Drug: Onartuzumab
Participants will receive onartuzumab 10 mg/kg IV infusion on Day 1 of every cycle (each cycle = 14 days) until disease progression, unacceptable toxicity, or participant or physician decision to discontinue treatment.
Other Name: MetMAb, RO5490258, PRO143966
Drug: Oxaliplatin
Participants will receive oxaliplatin 85 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Placebo Comparator: Placebo+mFOLFOX6
Participants will receive onartuzumab matching placebo + mFOLFOX6. Participants will receive a maximum of 12 cycles (each cycle is 14 days) of mFOLFOX6 with placebo. Participants whose disease has not progressed after 12 cycles of mFOLFOX6 with placebo will continue treatment with placebo until disease progression, unacceptable toxicity, or death.
Drug: 5-Fluoruracil
Participants will receive 5-fluorouracil 400 milligrams per square meter (mg/m^2) IV bolus and then 2400 mg/m^2 as a continuous IV infusion over 46-48 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Drug: Folinic acid
Participants will receive folinic acid 400 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Drug: Oxaliplatin
Participants will receive oxaliplatin 85 mg/m^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression or at the maximum of 12 cycles, whichever occurs first.
Drug: Placebo
Participants will receive onartuzumab matching placebo on Day 1 of every cycle (each cycle = 14 days) until disease progression, unacceptable toxicity, or participant or physician decision to discontinue treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable to curative therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Life expectancy greater than (>) 3 months
  • Presence of tissue sample for IHC assay of MET receptor and HER2 status
  • Tumor (primary or metastatic lesion) defined as MET-positive by IHC
  • Measurable disease or non-measurable but evaluable disease, according to the RECIST v1.1; Participants with peritoneal disease would generally be regarded as having evaluable disease and allowed to enter the trial
  • For women who are not postmenopausal or surgically sterile; agreement to use an adequate method of contraception (hormonal implant) during the treatment period and for at least 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin
  • For men: agreement to use a barrier method of contraception during the treatment period and for 90 days after the last dose of onartuzumab/placebo and 6 months after the last dose of oxaliplatin

Exclusion Criteria:

  • HER2-positive tumor (primary tumor or metastasis)
  • Previous chemotherapy for locally advanced or metastatic gastric carcinoma (adjuvant or neoadjuvant chemotherapy must be completed at least 6 months prior to randomization)
  • Prior treatment with investigational drugs that target the human growth factor (HGF) or MET pathway
  • History of another malignancy within the previous 5 years, except for appropriately treated and presumed cured carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, and localized prostate cancer
  • Pregnancy or lactation
  • Receipt of an investigational drug within 28 days prior to study start
  • Clinically significant gastrointestinal abnormalities, apart from gastric cancer, including uncontrolled inflammatory gastrointestinal diseases
  • Significant history of cardiac disease
  • Significant vascular disease
  • Serious active infection at the time of randomization, or other serious underlying medical conditions that would impair the ability of the participant to receive protocol treatment
  • Infection with human immunodeficiency virus, hepatitis B, or hepatitis C
  • Radiotherapy within 4 weeks before start of study treatment
  • Major surgery within 4 weeks before start of study treatment, without complete recovery
  • Any condition (psychological, geographical) that does not permit compliance with study and follow-up procedures
  • Peripheral neuropathy
  • Prior unanticipated severe reaction to fluoropyrimidine therapy
  • Known sensitivity or contraindication to any component of study treatment
  • Active gastrointestinal bleeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662869

  Show 125 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01662869     History of Changes
Other Study ID Numbers: YO28322  2012-001402-23 
Study First Received: August 8, 2012
Last Updated: November 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Fluorouracil
Antibodies, Monoclonal
Leucovorin
Levoleucovorin
Folic Acid
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hematinics

ClinicalTrials.gov processed this record on December 09, 2016