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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: September 1, 2016
Last verified: September 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

  Hide Study Locations
Locations
United States, California
Los Angeles, California, United States, 90095
United States, Colorado
Denver, Colorado, United States, 80218
United States, Florida
Fort Myers, Florida, United States, 33908
St Petersburg, Florida, United States, 33705
United States, Illinois
Chicago, Illinois, United States, 60637
United States, New York
Albany, New York, United States, 12206
New York, New York, United States, 10065
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45219
United States, Rhode Island
Providence, Rhode Island, United States, 02903
Providence, Rhode Island, United States, 02906
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Austin, Texas, United States, 78731
Tyler, Texas, United States, 75702
United States, Washington
Vancouver, Washington, United States, 98684
Australia, New South Wales
Port Macquarie, New South Wales, Australia, 2444
Sydney, New South Wales, Australia, 2139
Australia, Queensland
Herston, Queensland, Australia, 4029
Australia, Victoria
Box Hill, Victoria, Australia, 3128
East Bentleigh, Victoria, Australia, VIC 3165
Australia, Western Australia
Nedlands, Western Australia, Australia, 6009
Belgium
Brugge, Belgium, 8000
Leuven, Belgium, 3000
Sint-Niklaas, Belgium, 9100
Canada, Ontario
Hamilton, Ontario, Canada, L8L 2X2
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5B 1N9
Toronto, Ontario, Canada, M5G 1X5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Czech Republic
Brno, Czech Republic, 656 53
Olomouc, Czech Republic, 775 20
France
Angers, France, 49055
Avignon, France, 84918
Besancon, France, 25030
Brest, France, 29200
Clichy, France, 92118
Marseille, France, 13273
Paris, France, 75475
Paris, France, 75571
Paris, France, 75674
St Herblain, France, 44805
Toulouse, France, 31059
Germany
Bochum, Germany, 44892
Essen, Germany, 45122
Hamburg, Germany, 22767
Leipzig, Germany, 04103
Ludwigsburg, Germany, 71640
Mannheim, Germany, 68167
Marburg, Germany, 35043
München, Germany, 81675
Guatemala
Guatemala, Guatemala, 01010
Hong Kong
Hong Kong, Hong Kong, 852
Hong Kong, Hong Kong
Israel
Jerusalem, Israel, 91120-01
Ramat Gan, Israel, 5262100
Tel Aviv, Israel, 64239-06
Italy
Catanzaro, Calabria, Italy, 88100
Udine, Friuli-Venezia Giulia, Italy, 33100
Roma, Lazio, Italy, 00168
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20133
Torino, Piemonte, Italy, 10126
Firenze, Toscana, Italy, 50139
Prato, Toscana, Italy, 59100
Korea, Republic of
Seoul, Korea, Republic of, 02841
Seoul, Korea, Republic of, 03080
Seoul, Korea, Republic of, 05505
Seoul, Korea, Republic of, 06351
Seoul, Korea, Republic of, 06591
Seoul, Korea, Republic of, 120-749
Seoul, Korea, Republic of, 135-720
Malaysia
Kuala Lumpur, Malaysia, 59100
Sabah, Malaysia, 88996
Mexico
Aguascalientes, Mexico, 20230
Monterrey, Mexico, 64020
Oaxaca, Mexico, 68000
Panama
Panama, Panama, 0834-02723
Poland
Bydgoszcz, Poland, 85-796
Gdansk, Poland, 80-952
Krakow, Poland, 31-501
Lublin, Poland, 20-081
Rybnik, Poland, 44-200
Warszawa, Poland, 02-781
Russian Federation
Ivanovo, Russian Federation, 153040
Omsk, Russian Federation, 644013
Ryazan, Russian Federation, 390011
Samara, Russian Federation, 443031
Tula, Russian Federation, 300053
Singapore
Singapore, Singapore, 169610
Spain
Elche, Alicante, Spain, 03203
Santander, Cantabria, Spain, 39008
Barcelona, Spain, 08003
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Madrid, Spain, 28007
Madrid, Spain, 28046
Zaragoza, Spain, 50009
Switzerland
Luzern, Switzerland, 6004
Zürich, Switzerland, 8063
Taiwan
Changhua, Taiwan, 500
Kaohisung, Taiwan
Taichung, Taiwan, 404
Taichung, Taiwan, 407
Taipei, Taiwan, 00112
Taipei, Taiwan, 100
Taipei, Taiwan, 112
Thailand
Bangkok, Thailand, 10330
Bangkok, Thailand, 10400
Bangkok, Thailand, 10700
Chiang Rai, Thailand, 57000
Hat Yai, Thailand, 90110
Lopburi, Thailand, 15000
Turkey
Antalya, Turkey, 07070
Edirne, Turkey, 22770
Erzurum, Turkey, 25240
Malatya, Turkey, 44280
Samsun, Turkey, 55139
Sıhhiye, ANKARA, Turkey, 06100
United Kingdom
Bristol, United Kingdom, BS2 8ED
Cardiff, United Kingdom, CF14 2TL
London, United Kingdom, SW3 6JJ
Manchester, United Kingdom, M2O 4BX
Southampton, United Kingdom, SO16 6YD
Sutton, United Kingdom, SM2 5PT
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: September 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 September 27, 2016