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

NCT ID: NCT01662869

Last Updated: 2016-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

564 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2015-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Gastric Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

5-Fluoruracil

Intervention Type 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.

Folinic acid

Intervention Type 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

Intervention Type 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.

Oxaliplatin

Intervention Type 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.

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.

Group Type PLACEBO_COMPARATOR

5-Fluoruracil

Intervention Type 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.

Folinic acid

Intervention Type 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.

Oxaliplatin

Intervention Type 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.

Placebo

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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MetMAb, RO5490258, PRO143966

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Los Angeles, California, United States

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Denver, Colorado, United States

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Fort Myers, Florida, United States

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St. Petersburg, Florida, United States

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Chicago, Illinois, United States

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Albany, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Providence, Rhode Island, United States

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Providence, Rhode Island, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Tyler, Texas, United States

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Vancouver, Washington, United States

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Port Macquarie, New South Wales, Australia

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Sydney, New South Wales, Australia

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Herston, Queensland, Australia

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Box Hill, Victoria, Australia

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East Bentleigh, Victoria, Australia

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Nedlands, Western Australia, Australia

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Bruges, , Belgium

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Leuven, , Belgium

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Sint-Niklaas, , Belgium

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Brno, , Czechia

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Olomouc, , Czechia

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Angers, , France

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Avignon, , France

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Besançon, , France

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Brest, , France

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Clichy, , France

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Marseille, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Saint-Herblain, , France

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Toulouse, , France

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Bochum, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Leipzig, , Germany

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Ludwigsburg, , Germany

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Mannheim, , Germany

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Marburg, , Germany

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München, , Germany

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Guatemala City, , Guatemala

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Catanzaro, Calabria, Italy

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Udine, Friuli Venezia Giulia, Italy

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Rome, Lazio, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Turin, Piedmont, Italy

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Florence, Tuscany, Italy

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Prato, Tuscany, Italy

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Sabah, Sabah, Malaysia

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Kuala Lumpur, , Malaysia

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Aguascalientes, , Mexico

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Monterrey, , Mexico

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Oaxaca City, , Mexico

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Panama City, , Panama

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Krakow, , Poland

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Lublin, , Poland

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Rybnik, , Poland

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Warsaw, , Poland

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Ivanovo, , Russia

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Omsk, , Russia

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Ryazan, , Russia

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Samara, , Russia

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Tula, , Russia

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Singapore, , Singapore

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Elche, Alicante, Spain

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Barcelona, Barcelona, Spain

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Barcelona, Barcelona, Spain

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Barcelona, Barcelona, Spain

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Santander, Cantabria, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Zaragoza, Zaragoza, Spain

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Lucerne, , Switzerland

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Zurich, , Switzerland

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Changhua, , Taiwan

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Kaohisung, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Rai, , Thailand

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Hat Yai, , Thailand

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Lopburi, , Thailand

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Antalya, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Erzurum, , Turkey (Türkiye)

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Malatya, , Turkey (Türkiye)

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Samsun, , Turkey (Türkiye)

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Sıhhiye, Ankara, , Turkey (Türkiye)

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Bristol, , United Kingdom

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Cardiff, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Southampton, , United Kingdom

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Sutton, , United Kingdom

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Countries

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Brazil China Ukraine United States Australia Belgium Canada Czechia France Germany Guatemala Hong Kong Israel Italy Malaysia Mexico Panama Poland Russia Singapore South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 27918764 (View on PubMed)

Other Identifiers

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2012-001402-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

YO28322

Identifier Type: -

Identifier Source: org_study_id