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A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Patients With Recurrent Glioblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01632228
First received: June 28, 2012
Last updated: November 17, 2014
Last verified: November 2014
  Purpose

This randomized, double-blind, placebo-controlled, multicenter phase II study wi ll evaluate the safety and efficacy of onartuzumab (MetMAb) in combination with bevacizumab as compared to bevacizumab alone and of onartuzumab as monotherapy i n patients with recurrent glioblastoma. Patients will be randomized 1:1:1 to rec eive either placebo plus bevacizumab every 3 weeks, or onartuzumab plus bevacizu mab, or onartuzumab plus placebo. Anticipated time on study treatment is until d isease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Glioblastoma
Drug: bevacizumab
Drug: bevacizumab placebo
Drug: onartuzumab
Drug: onartuzumab placebo
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, Double-Blind, Placebo-Controlled, Multicenter Phase II Study Evaluating the Efficacy and Safety of Onartuzumab (MetMAb) in Combination With Bevacizumab or Onartuzumab Monotherapy in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival (investigator-assessed): onartuzumab + bevacizumab versus placebo + bevacizumab [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Progression-free survival (investigator-assessed) in subgroup with Met-positive glioblastoma: onartuzumab + bevacizumab versus placebo + bevacizumab [ Time Frame: 21 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival in all patients [ Time Frame: 21 months ] [ Designated as safety issue: Yes ]
  • Progression-free survival at 6 months (PFS-6) in all patients [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Objective response rate in all patients according to Response Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Duration of response in all patients [ Time Frame: 21 months ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of adverse events in all patients [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Overall survival rate at 9 months (OS-9) in all patients [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Immunogenicity: anti-therapeutic antibodies (ATAs) levels [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Overall survival in Met-positive glioblastoma patients [ Time Frame: 21 months ] [ Designated as safety issue: Yes ]
  • Overall survival rate at 9 months (OS-9) in Met-positive glioblastoma patients [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Progression-free survival at 6 months (PFS-6) in patients with Met positive tumors [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Objective response rate in patients with Met-positive tumors according to Response Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Duration of response in patients with Met-positive tumors [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events in patients with Met-positive tumors [ Time Frame: 21 months ] [ Designated as safety issue: No ]
  • Immunogenicity: anti-therapeutic antibodies (ATAs) levels [ Time Frame: Pre-dose and 30 min post-dose Day 1, Cycles 1-4 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmin/Cmax [ Time Frame: Pre-dose and 30 min post-dose Day 1, Cycles 1-4 ] [ Designated as safety issue: No ]

Enrollment: 135
Study Start Date: June 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A: placebo + bevacizumab Drug: bevacizumab
Intravenous repeating dose
Drug: onartuzumab placebo
Intravenous repeating dose
Experimental: B: onartuzumab + bevacizumab Drug: bevacizumab
Intravenous repeating dose
Drug: onartuzumab
Intravenous repeating dose
Experimental: C: onartuzumab + placebo Drug: bevacizumab placebo
Intravenous repeating dose
Drug: onartuzumab
Intravenous repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically confirmed glioblastoma at first recurrence after concurrent or adjuvant chemoradiotherapy
  • Imaging confirmation of first tumor progression or regrowth as defined by RANO criteria
  • Prior treatment with temozolomide
  • No more than one prior chemotherapy
  • No prior treatment with bevacizumab or other VEGF- or VEGF-receptor-targeted agent
  • No prior exposure to experimental treatment targeting either HGF or Met pathway
  • No prior treatment with prolifeprospan 20 with carmustine wafer
  • No prior intracerebral agent
  • Recovery from the toxic effects of prior therapy
  • No evidence of recent haemorrhage on baseline MRI of the brain
  • No need for urgent palliative intervention for primary disease (e.g. impending herniation)
  • Karnofsky performance status >/= 70%
  • Stable or decreasing dose of corticosteroids within 5 days prior to randomization
  • Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
  • Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: surgery must have confirmed the recurrence, a minimum of 28 days must have elapsed from the day of surgery to randomization and for core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization, and craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization
  • Availability of formalin fixed paraffin embedded tumor tissue representative of glioblastoma

Exclusion Criteria:

  • Pregnant or lactating women
  • Inadequate hematologic, renal or liver function
  • History or presence of serious cardio-vascular disease
  • New York Heart Association Grade II or greater congestive heart failure
  • History of another malignancy in the previous 3 years, except for in situ cancer or basal or squamous cell skin cancer
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg while on antihypertensive medication)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
  • Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
  • Known hypersensitivity to any excipients of onartuzumab or bevacizumab
  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: NCT01632228

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35294
United States, California
Los Angeles, California, United States, 90095
Los Angeles, California, United States, 90048
San Francisco, California, United States, 94143
Stanford, California, United States, 94305
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Englewood, Florida, United States, 34223
Saint Petersburg, Florida, United States, 33705
Tampa, Florida, United States, 33612-9497
United States, Illinois
Chicago, Illinois, United States, 60611
Evanston, Illinois, United States, 60201
United States, Michigan
Detroit, Michigan, United States, 48202
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45220
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75246
United States, Virginia
Charlottesville, Virginia, United States, 22908
Richmond, Virginia, United States, 23230
United States, Washington
Seattle, Washington, United States, 98101
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3A 2B4
Sherbrooke, Quebec, Canada, J1H 5N4
France
Bobigny, France, 93009
Bron, France, 69677
Lille, France, 59037
Marseille, France, 13385
Montpellier, France, 34298
Nancy, France, 54000
Paris, France, 75651
Saint Herblain, France, 44805
Toulouse Cedex 9, France, 31059
Germany
Berlin, Germany, 13353
Bonn, Germany, 53127
Frankfurt am Main, Germany, 60528
Hamburg, Germany, 20246
Ibbenbühren, Germany, 49479
Köln, Germany, 50937
Mainz, Germany, 55131
München, Germany, 81377
Oldenburg, Germany, 26121
Italy
Bologna, Emilia-Romagna, Italy, 40133
Cesena, Emilia-Romagna, Italy, 47023
Parma, Emilia-Romagna, Italy, 43100
Brescia, Lombardia, Italy, 25123
Milano, Lombardia, Italy, 20122
Milano, Lombardia, Italy, 20133
Torino, Piemonte, Italy, 10126
Pisa, Toscana, Italy, 56100
Spain
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Pamplona, Navarra, Spain, 31008
Barcelona, Spain, 08036
Barcelona, Spain, 08916
Madrid, Spain, 28034
Madrid, Spain, 28050
Malaga, Spain, 29010
Switzerland
Geneve, Switzerland, 1211
Zürich, Switzerland, 8091
United Kingdom
Bristol, United Kingdom, BS2 8ED
London, United Kingdom, W1G 6AD
London, United Kingdom, N6A 4L6
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01632228     History of Changes
Other Study ID Numbers: GO27819, 2011-005912-27
Study First Received: June 28, 2012
Last Updated: November 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Antibodies, Monoclonal
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014