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

NCT01662869 | Completed Phase 3

• 2 other identifiers: YO283222012-001402-23
• Study Type: interventional
• Target: 564
• Locations: 24 countries
• Sites: 125

Brief Summary

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup

  Baseline until death (up to approximately 38 months overall)

• OS in the Intent-To-Treat (ITT) Population

  Baseline until death (up to approximately 38 months overall)

Secondary Outcomes (14)

• Duration of Response, as Assessed by Investigator Using RECIST v1.1

  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)

• 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

  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)

• Percentage of Participants with Adverse Events

  Baseline up to approximately 38 months

• Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) of Onartuzumab

  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)

• Change from Baseline in ATAs Level of Onartuzumab

  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)

Study Arms (2)

Onartuzumab+mFOLFOX6

EXPERIMENTAL

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; Drug: Folinic acid; Drug: Onartuzumab; Drug: Oxaliplatin

Placebo+mFOLFOX6

PLACEBO COMPARATOR

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; Drug: Folinic acid; Drug: Oxaliplatin; Drug: Placebo

Interventions

5-Fluoruracil DRUG

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.

Onartuzumab+mFOLFOX6; Placebo+mFOLFOX6

Folinic acid DRUG

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.

Onartuzumab+mFOLFOX6; Placebo+mFOLFOX6

Onartuzumab DRUG

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.

Also known as: MetMAb, RO5490258, PRO143966

Onartuzumab+mFOLFOX6

Oxaliplatin DRUG

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.

Onartuzumab+mFOLFOX6; Placebo+mFOLFOX6

Placebo DRUG

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.

Placebo+mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Genentech, Inc.: collaborator

Study Sites (125)

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Los Angeles, California, 90095, United States

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Denver, Colorado, 80218, United States

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Fort Myers, Florida, 33908, United States

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St. Petersburg, Florida, 33705, United States

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Chicago, Illinois, 60637, United States

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Albany, New York, 12206, United States

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New York, New York, 10065, United States

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Durham, North Carolina, 27710, United States

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Cincinnati, Ohio, 45219, United States

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Providence, Rhode Island, 02903, United States

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Providence, Rhode Island, 02906, United States

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Nashville, Tennessee, 37203, United States

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Austin, Texas, 78731, United States

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Tyler, Texas, 75702, United States

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Vancouver, Washington, 98684, United States

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Port Macquarie, New South Wales, 2444, Australia

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Sydney, New South Wales, 2139, Australia

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Herston, Queensland, 4029, Australia

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Box Hill, Victoria, 3128, Australia

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East Bentleigh, Victoria, VIC 3165, Australia

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Nedlands, Western Australia, 6009, Australia

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Bruges, 8000, Belgium

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Leuven, 3000, Belgium

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Sint-Niklaas, 9100, Belgium

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Hamilton, Ontario, L8L 2X2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5B 1N9, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Brno, 656 53, Czechia

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Olomouc, 775 20, Czechia

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Angers, 49055, France

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Avignon, 84918, France

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Besançon, 25030, France

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Brest, 29200, France

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Clichy, 92118, France

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Marseille, 13273, France

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Paris, 75475, France

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Paris, 75571, France

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Paris, 75674, France

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Saint-Herblain, 44805, France

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Toulouse, 31059, France

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Bochum, 44892, Germany

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Essen, 45122, Germany

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Hamburg, 22767, Germany

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Leipzig, 04103, Germany

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Ludwigsburg, 71640, Germany

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Mannheim, 68167, Germany

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Marburg, 35043, Germany

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München, 81675, Germany

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Guatemala City, 01010, Guatemala

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Hong Kong, 852, Hong Kong

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Hong Kong, Hong Kong

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Jerusalem, 91120-01, Israel

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Ramat Gan, 5262100, Israel

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Tel Aviv, 64239-06, Israel

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Catanzaro, Calabria, 88100, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Rome, Lazio, 00168, Italy

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Milan, Lombardy, 20132, Italy

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Milan, Lombardy, 20133, Italy

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Turin, Piedmont, 10126, Italy

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Florence, Tuscany, 50139, Italy

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Prato, Tuscany, 59100, Italy

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Sabah, Sabah, 88996, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Aguascalientes, 20230, Mexico

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Monterrey, 64020, Mexico

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Oaxaca City, 68000, Mexico

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Panama City, 0834-02723, Panama

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Bydgoszcz, 85-796, Poland

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Gdansk, 80-952, Poland

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Krakow, 31-501, Poland

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Lublin, 20-081, Poland

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Rybnik, 44-200, Poland

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Warsaw, 02-781, Poland

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Ivanovo, 153040, Russia

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Omsk, 644013, Russia

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Ryazan, 390011, Russia

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Samara, 443031, Russia

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Tula, 300053, Russia

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Singapore, 169610, Singapore

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Seoul, 120-749, South Korea

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Seoul, 135-720, South Korea

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Elche, Alicante, 03203, Spain

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Barcelona, Barcelona, 08003, Spain

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08036, Spain

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Santander, Cantabria, 39008, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28046, Spain

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Zaragoza, Zaragoza, 50009, Spain

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Lucerne, 6004, Switzerland

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Zurich, 8063, Switzerland

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Changhua, 500, Taiwan

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Kaohisung, Taiwan

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Taichung, 404, Taiwan

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Taichung, 407, Taiwan

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Taipei, 00112, Taiwan

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Taipei, 100, Taiwan

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Taipei, 112, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Rai, 57000, Thailand

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Hat Yai, 90110, Thailand

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Lopburi, 15000, Thailand

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Antalya, 07070, Turkey (Türkiye)

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Edirne, 22770, Turkey (Türkiye)

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Erzurum, 25240, Turkey (Türkiye)

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Malatya, 44280, Turkey (Türkiye)

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Samsun, 55139, Turkey (Türkiye)

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Sıhhiye, Ankara, 06100, Turkey (Türkiye)

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Bristol, BS2 8ED, United Kingdom

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Cardiff, CF14 2TL, United Kingdom

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London, SW3 6JJ, United Kingdom

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Manchester, M2O 4BX, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Related Publications (1)

• Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, Bruey JM, Smith D, McCaffery I, Shames DS, Phan S, Cunningham D. Effect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET-Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial. JAMA Oncol. 2017 May 1;3(5):620-627. doi: 10.1001/jamaoncol.2016.5580.

  PMID: 27918764 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Leucovorin; onartuzumab; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2012
• First Posted: August 10, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

FR (11); AU (6); HK (2); CH (2); MY (2); CZ (2); PA (1); RU (5); SG (1); TW (7); ME (3); TH (6); IT (8); DE (8); ES (8); GU (1); BE (3); PL (6); TU (6); GB (6); CA (6); US (15); IL (3); KR (7)