A Study of Onartuzumab (MetMAb) in Combination With mFOLFOX6 in Patients With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Negative Gastroesophageal Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: Onartuzumab (MetMAb)
* Drug: Oxaliplatin
* Drug: Folinic acid
* Drug: Levofolinic acid
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Onartuzumab (MetMAb) with mFOLFOX6<br>Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin) | Drug: Onartuzumab (MetMAb)<br>* Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Oxaliplatin<br>* Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Folinic acid<br>* Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Levofolinic acid<br>* If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>|
| Placebo Comparator: Placebo with mFOLFOX6<br>Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin) | Drug: Placebo<br>* Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Oxaliplatin<br>* Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Folinic acid<br>* Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: Levofolinic acid<br>* If folinic acid is unavailable: levofolinic acid 200 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil 400 mg/m2 IV followed by 2400 mg/m2 IV infusion every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) in all patients |  | Up to 18 months | 
| Progression-free survival (PFS) in patients with Met-positive tumors |  | Up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: incidence of adverse events |  | 18 months | 
| Overall survival (OS) |  | 18 months | 
| Overall response rate (ORR) |  | 18 months | 
| Duration of response (DOR) |  | 18 months |