A Randomized, Phase II, 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 Gastroesophageal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Onartuzumab (MetMAb)
- Conditions
- Gastric Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 123
- Primary Endpoint
- Progression-free survival (PFS) in all patients
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This randomized, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with mFOLFOX6 in patients with metastatic HER2-negative adenocarcinoma of the stomach or gastroesophageal junction. Patients will be randomized in a 1:1 ratio to receive either onartuzumab (MetMAb) or placebo in combination with mFOLFOX6. Patients may continue to receive onartuzumab (MetMAb) or placebo until disease progression, unacceptable toxicity, patient or physician decision to discontinue treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult patients, 18 years of age and older
- •Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable for curative therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Life expectancy \>3 months
- •Presence of tissue sample for immunohistochemistry assay of Met receptor and HER2 status (if unknown)
- •Radiographic evidence of disease; measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1); Patients 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 (e.g., 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
- •Adequate laboratory values
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 hepatocyte growth factor (HGF) or Met pathway
- •History of other 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
- •Receipt of an investigational drug within 28 days prior to study start
- •Clinically significant gastrointestinal abnormalities, except from gastric cancer (e.g., Crohn's disease)
- •Significant history of cardiac disease
- •Significant vascular disease
- •Infection with human immunodeficiency virus, hepatitis B, or hepatitis C
Arms & Interventions
Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Onartuzumab (MetMAb)
Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Oxaliplatin
Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Folinic acid
Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Levofolinic acid
Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: 5-Fluorouracil
Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Placebo
Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Oxaliplatin
Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Folinic acid
Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: Levofolinic acid
Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)
Intervention: 5-Fluorouracil
Outcomes
Primary Outcomes
Progression-free survival (PFS) in all patients
Time Frame: Up to 18 months
Progression-free survival (PFS) in patients with Met-positive tumors
Time Frame: Up to 18 months
Secondary Outcomes
- Overall response rate (ORR)(18 months)
- Duration of response (DOR)(18 months)
- Overall survival (OS)(18 months)
- Safety: incidence of adverse events(18 months)