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

NCT01590719 | Completed Phase 2

• 2 other identifiers: YO282522012-000858-57
• Study Type: interventional
• Target: 123
• Locations: 6 countries
• Sites: 36

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Safety: incidence of adverse events

  18 months

• Overall survival (OS)

  18 months

• Overall response rate (ORR)

  18 months

• Duration of response (DOR)

  18 months

Study Arms (2)

Onartuzumab (MetMAb) with mFOLFOX6

EXPERIMENTAL

Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)

Drug: Onartuzumab (MetMAb); Drug: Oxaliplatin; Drug: Folinic acid; Drug: Levofolinic acid; Drug: 5-Fluorouracil

Placebo with mFOLFOX6

PLACEBO COMPARATOR

Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid \[leucovorin\], and oxaliplatin)

Drug: Placebo; Drug: Oxaliplatin; Drug: Folinic acid; Drug: Levofolinic acid; Drug: 5-Fluorouracil

Interventions

Placebo DRUG

Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Placebo with mFOLFOX6

Onartuzumab (MetMAb) DRUG

Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Onartuzumab (MetMAb) with mFOLFOX6

Oxaliplatin DRUG

Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Onartuzumab (MetMAb) with mFOLFOX6; Placebo with mFOLFOX6

Folinic acid DRUG

Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment

Onartuzumab (MetMAb) with mFOLFOX6; Placebo with mFOLFOX6

Levofolinic acid DRUG

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

Onartuzumab (MetMAb) with mFOLFOX6; Placebo with mFOLFOX6

5-Fluorouracil DRUG

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

Onartuzumab (MetMAb) with mFOLFOX6; Placebo with mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Genentech, Inc.: collaborator

Study Sites (36)

Unknown Facility

Denver, Colorado, 80218, United States

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New Haven, Connecticut, 06520, United States

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Fort Myers, Florida, 33908, United States

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St. Petersburg, Florida, 33705, United States

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Chicago, Illinois, 60637, United States

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Niles, Illinois, 60714, United States

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Albany, New York, 12206, United States

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New York, New York, 10065, United States

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Cincinnati, Ohio, 45219, United States

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Nashville, Tennessee, 37203, United States

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Austin, Texas, 78731, United States

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Bedford, Texas, 76022, United States

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Garland, Texas, 77060, United States

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The Woodlands, Texas, 77380, United States

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Tyler, Texas, 75702, United States

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Fairfax, Virginia, 22031, United States

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Richmond, Virginia, 23226, United States

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Vancouver, Washington, 98684, United States

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Sydney, New South Wales, 2139, Australia

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Herston, Queensland, 4029, Australia

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Woodville South, South Australia, 5011, Australia

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East Bentleigh, Victoria, VIC 3165, Australia

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Heidelberg, Victoria, 3084, Australia

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Nedlands, Western Australia, 6009, Australia

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Singapore, 119228, Singapore

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Singapore, 169610, Singapore

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 135-720, South Korea

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Tainan, 00704, Taiwan

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Taipei, 00112, Taiwan

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Taipei, 100, Taiwan

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Taoyuan, 333, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Unknown Facility

Bangkok, 10700, Thailand

Location

Related Publications (1)

• Shah MA, Cho JY, Tan IB, Tebbutt NC, Yen CJ, Kang A, Shames DS, Bu L, Kang YK. A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction. Oncologist. 2016 Sep;21(9):1085-90. doi: 10.1634/theoncologist.2016-0038. Epub 2016 Jul 8.

  PMID: 27401892 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

onartuzumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2012
• First Posted: May 3, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: August 9, 2016

Record last verified: 2016-08

Locations

US (18); TH (3); AU (6); TW (4); KR (3); SG (2)