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

Roche

Status and phase: Completed; Phase 3

Conditions: Gastric Cancer

Treatments: Drug: Onartuzumab; Drug: Folinic acid; Drug: Placebo; Drug: Oxaliplatin; Drug: 5-Fluoruracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01662869

YO28322

2012-001402-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 564 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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564 participants in 2 patient groups, including a placebo group

Onartuzumab+mFOLFOX6

Experimental group

Description:

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.

Treatment:

Drug: Folinic acid

Drug: 5-Fluoruracil

Drug: Oxaliplatin

Drug: Onartuzumab

Placebo+mFOLFOX6

Placebo Comparator group

Description:

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:

Drug: Folinic acid

Drug: 5-Fluoruracil

Drug: Placebo

Drug: Oxaliplatin