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A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients (CheckMate 143)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02017717
First received: December 17, 2013
Last updated: December 6, 2016
Last verified: October 2016
  Purpose
The purpose of the study is to compare the efficacy and safety of nivolumab administered alone versus bevacizumab in patients diagnosed with recurrent glioblastoma (a type of brain cancer, also known as GBM), and to evaluate the safety and tolerability of nivolumab administered alone or in combination with ipilimumab in patients with different lines of GBM therapy.

Condition Intervention Phase
Recurrent Glioblastoma
Biological: Nivolumab
Biological: Bevacizumab
Biological: Ipilimumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 3 Open Label Study of Nivolumab Versus Bevacizumab and Multiple Phase 1 Safety Cohorts of Nivolumab or Nivolumab in Combination With Ipilimumab Across Different Lines of Glioblastoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Cohorts 1,1b, 1c and 1d : Safety and tolerability based on drug related events leading to permanent discontinuation prior to completing 4 doses [ Time Frame: Approximately up to 8 months ] [ Designated as safety issue: Yes ]
  • Cohort 2: Overall Survival (OS) [ Time Frame: Approximately 36 months ] [ Designated as safety issue: No ]

    OS of Nivolumab versus Bevacizumab.

    Overall Survival is defined as the time between the date of randomization and the date of death due to any cause



Secondary Outcome Measures:
  • Cohort 2: Overall Survival rate (OS) [ Time Frame: Approximately 36 months ] [ Designated as safety issue: No ]
    Comparing OS between Nivolumab and Bevacizumab

  • Cohort 2: Progression Free Survival (PFS) [ Time Frame: Approximately 36 months ] [ Designated as safety issue: No ]

    Comparing PFS between Nivolumab and Bevacizumab

    PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause


  • Cohort 2: Objective Response Rate(ORR) [ Time Frame: Approximately 36 months ] [ Designated as safety issue: No ]

    Comparing ORR between Nivolumab and Bevacizumab

    ORR is defined as the number of subjects whose best overall response (BOR) is Complete Response (CR) or Partial Response (PR) divided by all randomized subjects



Estimated Enrollment: 440
Study Start Date: January 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm N:Nivolumab
Cohort 1, 1c, 1d and 2: Nivolumab 3mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity
Biological: Nivolumab
Other Name: BMS-936558
Experimental: Arm N + I:Nivolumab + Ipilimumab

Cohort 1: Nivolumab 1mg/kg + Ipilimumab 3mg/kg intravenously every 3 weeks x 4 doses, then Nivolumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity

Cohort 1b: Nivolumab 3mg/kg + Ipilimumab 1mg/kg intravenously every 3 weeks for 4 doses, then Nivolumab 3mg/kg every 2 weeks thereafter until disease progression or unacceptable toxicity

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Other Name: Yervoy
Active Comparator: Arm B: Bevacizumab
Cohort 2: Bevacizumab 10 mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity
Biological: Bevacizumab
Other Name: Avastin

Detailed Description:
Allocation: Randomized (Cohort 1 and 2), Non-Randomized (Cohorts 1b, 1c and 1d)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Subjects with histologically confirmed Grade IV malignant glioma
  • Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
  • First recurrence of GBM (Cohorts 1, 1b and 2 only)
  • First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
  • First diagnosis of unmethylated MGMT GBM (Cohort 1d and Cohort 1c Part B only)
  • Karnofsky performance score of 70 or higher

Exclusion Criteria:

  • More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
  • Any recurrence of GBM (Cohorts 1c and 1d only)
  • Presence of extracranial metastatic or leptomeningeal disease
  • Active, known or suspected autoimmune disease
  • Clinically significant cardiovascular disease
  • Prior bevacizumab or other Vascular Endothelial Growth Factor (VEGF) or anti-angiogenic treatment (Cohort 2 only)
  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: NCT02017717

  Hide Study Locations
Locations
United States, Alabama
University Of Alabama At Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
Ucla Neuro-Oncology Program
Los Angeles, California, United States, 90095
University Of California San Francisco
San Francisco, California, United States, 94143
United States, Colorado
University Of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Medstar Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute.
Atlanta, Georgia, United States, 30322
United States, Maryland
The Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Inst
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System
Detriot, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
Preston Robert Tisch Brain Tumor Center At Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Of Cleveland
Cleveland, Ohio, United States, 44106
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University Of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States, 77030
United States, Virginia
University Of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Swedish Neuroscience Institute
Seattle, Washington, United States, 98122
Australia, New South Wales
Local Institution
Liverpool, New South Wales, Australia, 2017
Australia, Victoria
Local Institution
East Bentleigh, Victoria, Australia, 3165
Local Institution
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
Local Institution
Nedlands, Western Australia, Australia, 6009
Belgium
Local Institution
Brussels, Belgium, 1090
Local Institution
Bruxelles, Belgium, 1200
Denmark
Aarhus University Hospital
Aarhus C, Denmark, 8000
Odense University Hospital
Odense C, Denmark, 5000
France
Local Institution
Bobigny, France, 93000
Local Institution
Bron cedex, France, 69677
Local Institution
Marseille Cedex 5, France, 13385
Local Institution
Paris cedex 13, France, 75651
Germany
Universitaetsklinikum Bonn
Bonn, Germany, 53105
Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main
Frankfurt Am Main, Germany, 60528
Local Institution
Heidelberg, Germany, 69120
Universitaetsklinikum Muenster
Muenster, Germany, 48149
Italy
Local Institution
Bologna, Italy, 40139
Local Institution
Milano, Italy, 20133
Local Institution
Siena, Italy, 53100
Local Institution
Torino, Italy, 10126
Netherlands
Local Institution
Amsterdam, Netherlands, 1066CX
Local Institution
Groningen, Netherlands, 9713 GZ
Poland
Local Institution
Gdansk, Poland, 80-952
Local Institution
Warszawa, Poland, 02-781
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Madrid, Spain, 28009
Local Institution
Madrid, Spain, 28041
Local Institution
Pamplona, Spain, 31008
Switzerland
Centre Hospitalier Universitaire Vaudois (Chuv)
Lausanne, Switzerland, BT 02252
Universitaetsspital Zurich
Zuerich, Switzerland, 8091
United Kingdom
Local Institution
London, Greater London, United Kingdom, NW1 2PG
Local Institution
Manchester, Greater Manchester, United Kingdom, M20 4BX
Local Institution
Wirral, Merseyside, United Kingdom, L63 4JY
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02017717     History of Changes
Other Study ID Numbers: CA209-143  2013-003738-34 
Study First Received: December 17, 2013
Last Updated: December 6, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ministry of Health
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Spain: Spanish Agency of Medicines
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Switzerland: Federal Office of Public Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Poland: National Institute of Medicines
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

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

ClinicalTrials.gov processed this record on December 08, 2016