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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01662869




Registration number
NCT01662869
Ethics application status
Date submitted
8/08/2012
Date registered
10/08/2012
Date last updated
2/11/2016

Titles & IDs
Public title
A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer
Scientific 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
Secondary ID [1] 0 0
2012-001402-23
Secondary ID [2] 0 0
YO28322
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluoruracil
Treatment: Drugs - Folinic acid
Treatment: Drugs - Onartuzumab
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup
Timepoint [1] 0 0
Baseline until death (up to approximately 38 months overall)
Primary outcome [2] 0 0
OS in the Intent-To-Treat (ITT) Population
Timepoint [2] 0 0
Baseline until death (up to approximately 38 months overall)
Secondary outcome [1] 0 0
Duration of Response, as Assessed by Investigator Using RECIST v1.1
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Percentage of Participants with Adverse Events
Timepoint [3] 0 0
Baseline up to approximately 38 months
Secondary outcome [4] 0 0
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) of Onartuzumab
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Change from Baseline in ATAs Level of Onartuzumab
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Minimum Serum Concentration of Onartuzumab (Cmin)
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Maximum Serum Concentration (Cmax) of Onartuzumab
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 38 months overall)
Secondary outcome [9] 0 0
PFS, as Assessed by Investigator Using RECIST v1.1 in ITT Population
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Percentage of Participants with a Tumor Response of CR or PR as Determined by the Investigator Using RECIST v1.1 in ITT Population
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (EORTC QLQ-C30) Score
Timepoint [12] 0 0
Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months
Secondary outcome [13] 0 0
EORTC QLQ-Gastric cancer Specific Quality of Life Questionnaire (EORTC QLQ-STOC22) Score
Timepoint [13] 0 0
Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months
Secondary outcome [14] 0 0
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Score
Timepoint [14] 0 0
Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2015
Sample size
Target
Accrual to date
Final
564
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- Port Macquarie
Recruitment hospital [2] 0 0
- Sydney
Recruitment hospital [3] 0 0
- Herston
Recruitment hospital [4] 0 0
- Box Hill
Recruitment hospital [5] 0 0
- East Bentleigh
Recruitment hospital [6] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2139 - Sydney
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
VIC 3165 - East Bentleigh
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Rhode Island
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Belgium
State/province [12] 0 0
Brugge
Country [13] 0 0
Belgium
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Leuven
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Belgium
State/province [14] 0 0
Sint-Niklaas
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Czech Republic
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Brno
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Czech Republic
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Olomouc
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France
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Angers
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France
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Avignon
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France
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Besancon
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France
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Brest
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France
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Clichy
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France
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Paris
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France
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St Herblain
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Toulouse
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Bochum
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Essen
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Hamburg
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Germany
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Leipzig
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Mannheim
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Germany
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Marburg
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Germany
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München
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Guatemala
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Guatemala
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Hong Kong
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Ramat Gan
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Tel Aviv
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Friuli-Venezia Giulia
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Lazio
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Italy
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Lombardia
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Piemonte
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Toscana
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Seoul
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Rybnik
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Russian Federation
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Omsk
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Russian Federation
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Ryazan
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Russian Federation
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Samara
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Tula
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Singapore
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Alicante
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Cantabria
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Barcelona
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Madrid
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Zaragoza
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Switzerland
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Luzern
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Zürich
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Changhua
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Taiwan
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Kaohisung
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Taichung
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Chiang Rai
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Thailand
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Hat Yai
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Thailand
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Lopburi
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Turkey
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Antalya
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Edirne
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Turkey
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Erzurum
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Malatya
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Turkey
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Samsun
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Turkey
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Sihhiye, ANKARA
Country [87] 0 0
United Kingdom
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Bristol
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United Kingdom
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Cardiff
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Southampton
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01662869
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries