Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01662869
Recruitment Status : Completed
First Posted : August 10, 2012
Last Update Posted : November 2, 2016
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE August 8, 2012
First Posted Date  ICMJE August 10, 2012
Last Update Posted Date November 2, 2016
Study Start Date  ICMJE November 2012
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2016)
  • Overall survival (OS) in the MET Immunohistochemistry (IHC) 2+/3+ Participant Subgroup [ Time Frame: Baseline until death (up to approximately 38 months overall) ]
  • OS in the Intent-To-Treat (ITT) Population [ Time Frame: Baseline until death (up to approximately 38 months overall) ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2012)
  • Overall survival (OS) in the Met IHC 2+/3+ patient subgroup [ Time Frame: Approximately 38 months ]
  • Overall survival in the intent-to-treat population [ Time Frame: Approximately 38 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2016)
  • 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) ]
  • 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) ]
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 38 months ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2012)
  • Progression-free survival [ Time Frame: Approximately 38 months ]
  • Overall response rate (ORR) [ Time Frame: Approximately 38 months ]
  • Safety: incidence of adverse events [ Time Frame: Approximately 38 months ]
  • European Organization for Research and Treatment Cancer - Quality of life questionnaire [ Time Frame: Approximately 38 months ]
  • European Organization for Research and Treatment Cancer - Gastric cancer-specific quality of life questionnaire [ Time Frame: Approximately 38 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: 5-Fluoruracil
    • Drug: Folinic acid
    • Drug: Onartuzumab
    • Drug: Oxaliplatin
  • 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.
    Interventions:
    • Drug: 5-Fluoruracil
    • Drug: Folinic acid
    • Drug: Oxaliplatin
    • Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 31, 2015)
564
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2012)
800
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Czech Republic,   France,   Germany,   Guatemala,   Hong Kong,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Mexico,   Panama,   Poland,   Russian Federation,   Singapore,   Spain,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries Brazil,   China,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT01662869
Other Study ID Numbers  ICMJE YO28322
2012-001402-23 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP