Clinical trial NCT01662869: A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2012-08-10
Enrollment: 564
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup
timeFrame: Baseline until death (up to approximately 38 months overall)
measure: OS in the Intent-To-Treat (ITT) Population
timeFrame: Baseline until death (up to approximately 38 months overall)
Secondary outcomes:
measure: Duration of Response, as Assessed by Investigator Using RECIST v1.1
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline up to approximately 38 months
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) of Onartuzumab
timeFrame: 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)
measure: Change from Baseline in ATAs Level of Onartuzumab
timeFrame: 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)
measure: Minimum Serum Concentration of Onartuzumab (Cmin)
timeFrame: 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)
measure: Maximum Serum Concentration (Cmax) of Onartuzumab
timeFrame: 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)
measure: 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
timeFrame: Baseline up to disease progression or death due to any cause, whichever occurs first (up to approximately 38 months overall)
measure: PFS, as Assessed by Investigator Using RECIST v1.1 in ITT Population
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Percentage of Participants with a Tumor Response of CR or PR as Determined by the Investigator Using RECIST v1.1 in ITT Population
timeFrame: 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)
measure: European Organization for Research and Treatment Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (EORTC QLQ-C30) Score
timeFrame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months
measure: EORTC QLQ-Gastric cancer Specific Quality of Life Questionnaire (EORTC QLQ-STOC22) Score
timeFrame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months
measure: European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Score
timeFrame: Day 1 of each treatment cycle (cycle length = 14 days) up to approximately 38 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Fort Myers
country: United States
state: Florida
city: St Petersburg
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Providence
country: United States
state: Rhode Island
city: Providence
country: United States
state: Rhode Island
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Vancouver
country: United States
state: Washington
city: Port Macquarie
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Box Hill
country: Australia
state: Victoria
city: East Bentleigh
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Brugge
country: Belgium
city: Leuven
country: Belgium
city: Sint-Niklaas
country: Belgium
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Brno
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Angers
country: France
city: Avignon
country: France
city: Besancon
country: France
city: Brest
country: France
city: Clichy
country: France
city: Marseille
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: St Herblain
country: France
city: Toulouse
country: France
city: Bochum
country: Germany
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Leipzig
country: Germany
city: Ludwigsburg
country: Germany
city: Mannheim
country: Germany
city: Marburg
country: Germany
city: München
country: Germany
city: Guatemala
country: Guatemala
city: Hong Kong
country: Hong Kong
city: Hong Kong
country: Hong Kong
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Catanzaro
country: Italy
state: Calabria
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Firenze
country: Italy
state: Toscana
city: Prato
country: Italy
state: Toscana
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kuala Lumpur
country: Malaysia
city: Sabah
country: Malaysia
city: Aguascalientes
country: Mexico
city: Monterrey
country: Mexico
city: Oaxaca
country: Mexico
city: Panama
country: Panama
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Rybnik
country: Poland
city: Warszawa
country: Poland
city: Ivanovo
country: Russian Federation
city: Omsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Samara
country: Russian Federation
city: Tula
country: Russian Federation
city: Singapore
country: Singapore
city: Elche
country: Spain
state: Alicante
city: Santander
country: Spain
state: Cantabria
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Zaragoza
country: Spain
city: Luzern
country: Switzerland
city: Zürich
country: Switzerland
city: Changhua
country: Taiwan
city: Kaohisung
country: Taiwan
city: Taichung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Rai
country: Thailand
city: Hat Yai
country: Thailand
city: Lopburi
country: Thailand
city: Antalya
country: Turkey
city: Edirne
country: Turkey
city: Erzurum
country: Turkey
city: Malatya
country: Turkey
city: Samsun
country: Turkey
city: Sıhhiye, ANKARA
country: Turkey
city: Bristol
country: United Kingdom
city: Cardiff
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Southampton
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.