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

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01590719
First received: May 2, 2012
Last updated: August 4, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Gastric Cancer
Drug: Placebo
Drug: Onartuzumab (MetMAb)
Drug: Oxaliplatin
Drug: Folinic acid
Drug: Levofolinic acid
Drug: 5-Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival (PFS) in all patients [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) in patients with Met-positive tumors [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: incidence of adverse events [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Duration of response (DOR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 123
Study Start Date: July 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Onartuzumab (MetMAb) with mFOLFOX6
Onartuzumab (MetMAb) in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)
Drug: Onartuzumab (MetMAb)
Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Oxaliplatin
Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Folinic acid
Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Levofolinic acid
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
Drug: 5-Fluorouracil
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
Placebo Comparator: Placebo with mFOLFOX6
Placebo in combination with mFOLFOX6 (modified 5-fluorouracil, folinic acid [leucovorin], and oxaliplatin)
Drug: Placebo
Repeating intravenous dose until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Oxaliplatin
Oxaliplatin 85 mg/m2 IV every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Folinic acid
Folinic acid 400 mg/m2 every 2 weeks until disease progression, unacceptable toxicity, or patient or physician decision to discontinue treatment
Drug: Levofolinic acid
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
Drug: 5-Fluorouracil
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01590719

  Show 36 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01590719     History of Changes
Other Study ID Numbers: YO28252  2012-000858-57 
Study First Received: May 2, 2012
Last Updated: August 4, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Fluorouracil
Antibodies, Monoclonal
Leucovorin
Levoleucovorin
Folic Acid
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hematinics

ClinicalTrials.gov processed this record on August 30, 2016