A Study of Onartuzumab in Combination With mFOLFOX6 in Participants With Metastatic HER2-Negative and MET-Positive Gastroesophageal Cancer
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| ClinicalTrials.gov Identifier: NCT01662869 |
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Recruitment Status :
Completed
First Posted : August 10, 2012
Last Update Posted : November 2, 2016
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Sponsor:
Hoffmann-La Roche
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Gastric Cancer | Drug: 5-Fluoruracil Drug: Folinic acid Drug: Onartuzumab Drug: Oxaliplatin Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 564 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 Start Date : | November 2012 |
| Actual Primary Completion Date : | December 2015 |
| Actual Study Completion Date : | December 2015 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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. |
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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.
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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: 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. |
Primary Outcome Measures :
- 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) ]
Secondary Outcome Measures :
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01662869
Locations
Show 125 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT01662869 |
| Other Study ID Numbers: |
YO28322 2012-001402-23 ( EudraCT Number ) |
| First Posted: | August 10, 2012 Key Record Dates |
| Last Update Posted: | November 2, 2016 |
| Last Verified: | November 2016 |
Additional relevant MeSH terms:
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Stomach Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Leucovorin Folic Acid Oxaliplatin Fluorouracil Levoleucovorin |
Antineoplastic Agents Antidotes Protective Agents Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients Hematinics Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors |