A Study of the Efficacy and Safety of Nivolumab vs Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients at Different Stages of Treatment (CheckMate 143)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02017717
First received: December 17, 2013
Last updated: May 20, 2015
Last verified: May 2015
  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: June 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
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)
  • Any recurrence of GBM (Cohorts 1, 1b and 2 only)
  • First diagnosis of GBM with resectable disease (Cohorts 1c and 1d only)
  • Untreated unmethylated MGMT GBM (Cohort 1d only)
  • Karnofsky performance status (PS) ≥ 70

Exclusion Criteria:

  • More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
  • First 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 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

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Hide Study Locations
Locations
United States, Alabama
University Of Alabama At Birmingham Active, not recruiting
Birmingham, Alabama, United States, 35294
United States, California
Cedars Sinai Medical Center Active, not recruiting
Los Angeles, California, United States, 90048
Ucla Neuro-Oncology Program Recruiting
Los Angeles, California, United States, 90095
Contact: Timothy Cloughesy, Site 0009    310-794-3521      
University Of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Nicholas Butowski, Site 0014    415-353-2966      
United States, Colorado
University Of Colorado Cancer Center Active, not recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School Of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Joachim Baehring, Site 0001    203-785-5702      
United States, District of Columbia
Medstar Georgetown University Medical Center Active, not recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Solmaz Sahebjam, Site 0004    813-745-1689      
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Alfredo Voloschin, Site 0002    404-778-1900      
United States, Maryland
The Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Michael Lim, Site 0008    410-502-4081      
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Reardon, Site 0006    617-632-6749      
United States, Michigan
Henry Ford Health System Active, not recruiting
Detriot, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Daniel Lachance, Site 0025    507-538-1471      
United States, New York
Memorial Sloan Kettering Cancer Ctr Recruiting
New York, New York, United States, 10065
Contact: Antonio Omuro, Site 0003    212-639-7523      
United States, North Carolina
Levine Cancer Institute Active, not recruiting
Charlotte, North Carolina, United States, 28204
Preston Robert Tisch Brain Tumor Center At Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Gordana Vlahovic, Site 0007    919-668-2329      
United States, Ohio
Cleveland Clinic Active, not recruiting
Cleveland, Ohio, United States, 44195
University Hospitals Of Cleveland Active, not recruiting
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Thomas Jefferson University Active, not recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University Of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Scott Lindhorst, Site 0023    843-576-1006      
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Stephen Clark, Site 0005    615-936-5850      
United States, Texas
University Of Texas Md Anderson Cancer Ctr Active, not recruiting
Houston, Texas, United States, 77030
United States, Virginia
University Of Virginia Health System Active, not recruiting
Charlottesville, Virginia, United States, 22908
United States, Washington
Seattle Cancer Care Alliance Active, not recruiting
Seattle, Washington, United States, 9809
Swedish Neuroscience Institute Active, not recruiting
Seattle, Washington, United States, 98122
Australia, New South Wales
Local Institution Recruiting
Liverpool, New South Wales, Australia, 2017
Contact: Site 0035         
Australia, Victoria
Local Institution Recruiting
East Bentleigh, Victoria, Australia, 3165
Contact: Site 0034         
Local Institution Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Site 0033         
Australia, Western Australia
Local Institution Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Site 0032         
Belgium
Local Institution Recruiting
Brussels, Belgium, 1090
Contact: Site 0050         
Local Institution Recruiting
Bruxelles, Belgium, 1200
Contact: Site 0051         
Canada, British Columbia
Local Institution Not yet recruiting
Vancouver, British Columbia, Canada, V5Z4E6
Contact: Site 0073         
Canada, Ontario
Local Institution Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site 0071         
Canada, Quebec
Local Institution Not yet recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Site 0072         
Denmark
Aarhus University Hospital Active, not recruiting
Aarhus C, Denmark, 8000
Odense University Hospital Recruiting
Odense C, Denmark, 5000
Contact: Steinbjorn Hansen, Site 0057    +4565413988      
France
Local Institution Recruiting
Bobigny, France, 93000
Contact: Site 0068         
Local Institution Recruiting
Bron cedex, France, 69677
Contact: Site 0062         
Local Institution Recruiting
Marseilles, France, 13005
Contact: Site 0063         
Local Institution Recruiting
Paris cedex 13, France, 75651
Contact: Site 0064         
Germany
Universitaetsklinikum Bonn Recruiting
Bonn, Germany, 53105
Contact: Ulrich Herrlinger, Site 0037    +4922828719887      
Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main Recruiting
Frankfurt Am Main, Germany, 60528
Contact: Johannes Rieger, Site 0036    +4969630187711      
Local Institution Recruiting
Heidelberg, Germany, 69120
Contact: Site 0038         
Local Institution Recruiting
Muenster, Germany, 48149
Contact: Site 0041         
Italy
Local Institution Recruiting
Bologna, Italy, 40139
Contact: Site 0010         
Local Institution Recruiting
Milano, Italy, 20133
Contact: Site 0011         
Local Institution Recruiting
Siena, Italy, 53100
Contact: Site 0012         
Local Institution Recruiting
Torino, Italy, 10126
Contact: Site 0013         
Netherlands
Local Institution Recruiting
Amsterdam, Netherlands, 1066CX
Contact: Site 0067         
Local Institution Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Site 0066         
Poland
Local Institution Recruiting
Gdansk, Poland, 80-952
Contact: Site 0060         
Local Institution Not yet recruiting
Olsztyn, Poland, 10-228
Contact: Site 0069         
Local Institution Recruiting
Warszawa, Poland, 02-781
Contact: Site 0059         
Spain
Local Institution Active, not recruiting
Barcelona, Spain, 08035
Local Institution Active, not recruiting
Madrid, Spain, 28041
Local Institution Active, not recruiting
Madrid, Spain, 28009
Local Institution Active, not recruiting
Pamplona, Spain, 31008
Switzerland
Local Institution Recruiting
Lausanne, Switzerland, BT 02252
Contact: Site 0039         
Universitaetsspital Zurich Recruiting
Zuerich, Switzerland, 8091
Contact: Patrick Roth, Site 0040    +41442555511      
United Kingdom
Local Institution Recruiting
London, Greater London, United Kingdom, NW1 2PG
Contact: Site 0018         
Local Institution Recruiting
Manchester, Greater Manchester, United Kingdom, M20 4BX
Contact: Site 0015         
Local Institution Recruiting
Wirral, Merseyside, United Kingdom, L63 4JY
Contact: Site 0017         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

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: May 20, 2015
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
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015