A Randomized Study of Nivolumab Versus Bevacizumab and a Safety Study of Nivolumab or Nivolumab Combined With Ipilimumab in Adult Subjects With Recurrent Glioblastoma (GBM) (CheckMate 143)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02017717
First received: December 17, 2013
Last updated: October 13, 2014
Last verified: September 2014
  Purpose

The purposes of the study are to understand the

  1. Safety and tolerability of Nivolumab and Nivolumab in combination with Ipilimumab in a safety lead-in phase (Cohort 1, 1b) and
  2. The safety, tolerability and efficacy of Nivolumab versus Bevacizumab (Cohort 2) in patients diagnosed with recurrent glioblastoma (GBM).

Condition Intervention Phase
Recurrent Glioblastoma
Biological: Nivolumab
Biological: Ipilimumab
Biological: Bevacizumab
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 a Safety Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Adult Subjects With Recurrent Glioblastoma (GBM)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Cohort 1 and 1b: 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 32 months ] [ Designated as safety issue: No ]

    OS of Nivolumab, or Nivolumab in combination with Ipilimumab 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:
  • Overall Survival rate (OS) [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
    Comparing OS between Nivolumab and Bevacizumab

  • Progression Free Survival (PFS) [ Time Frame: Approximately 32 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


  • Objective Response Rate(ORR) [ Time Frame: Approximately 32 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: 260
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 and 2: Nivolumab solution intravenously 3mg/kg 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 solution 1mg/kg + Ipilimumab solution 3mg/kg intravenously once every 3 weeks for four doses Followed by Nivolumab solution 3mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity

Cohort 1b: Nivolumab solution 3mg/kg + Ipilimumab solution 1mg/kg intravenously once every 3 weeks for four doses Followed by Nivolumab solution 3mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Other Names:
  • Yervoy
  • BMS-734016
Active Comparator: Arm B: Bevacizumab
Cohort 2: Bevacizumab solution 10 mg/kg intravenously once every 2 weeks until disease progression or unacceptable toxicity
Biological: Bevacizumab
Other Name: Avastin

Detailed Description:

Number of Arms: 2 in cohort 1; 1 in cohort 1b 2 in cohort 2

Enrollment: 372 enrolled; 20 randomized to Cohort 1 and 20 assigned to Cohort 1b, 220 randomized to Cohort 2

Allocation: Randomized Controlled Trial: participants are assigned to intervention groups by chance (Cohort 1 and 2); non-randomized trial for Cohort 1b

  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
  • Documented first recurrence of GBM
  • Karnofsky performance status (PS) ≥ 70

Exclusion Criteria:

  • More than one recurrence of GBM
  • Presence of extracranial metastatic or leptomeningeal disease
  • Active, known or suspected autoimmune disease
  • Prior Bevacizumab or other anti-vascular growth factor (VEGF) or anti-angiogenic treatment
  • Clinically significant cardiovascular disease
  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, California
Ucla Neuro-Oncology Program Recruiting
Los Angeles, California, United States, 90095
Contact: Timothy Cloughesy, Site 0009    310-794-3521      
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, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Solmaz Sahebjam, Site 0004    813-745-4398      
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, 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
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, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Stephen Clark, Site 0005    615-936-5850      
Australia, New South Wales
Local Institution Not yet recruiting
Liverpool, New South Wales, Australia, 2017
Contact: Site 0035         
Australia, Victoria
Local Institution Not yet recruiting
East Bentleigh, Victoria, Australia, 3165
Contact: Site 0034         
Local Institution Not yet recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Site 0033         
Australia, Western Australia
Local Institution Not yet recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Site 0032         
Canada, British Columbia
Local Institution Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
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
Local Institution Active, not recruiting
Aarhus C, Denmark, 8000
Local Institution Not yet recruiting
Odense C, Denmark, 5000
Contact: Site 0057         
Germany
Local Institution Recruiting
Bonn, Germany, 53105
Contact: Site 0037         
Local Institution Recruiting
Frankfurt Am Main, Germany, 60528
Contact: Site 0036         
Local Institution Recruiting
Heidelberg, Germany, 69120
Contact: Site 0038         
Local Institution Recruiting
Muenster, Germany, 48149
Contact: Site 0041         
Italy
Local Institution Not yet recruiting
Bologna, Italy, 40139
Contact: Site 0010         
Local Institution Not yet recruiting
Milano, Italy, 20133
Contact: Site 0011         
Local Institution Not yet recruiting
Siena, Italy, 53100
Contact: Site 0012         
Local Institution Not yet recruiting
Torino, Italy, 10126
Contact: Site 0013         
Poland
Local Institution Not yet recruiting
Gdansk, Poland, 80-952
Contact: Site 0060         
Local Institution Not yet recruiting
Olsztyn, Poland, 10-228
Contact: Site 0069         
Local Institution Not yet recruiting
Warszawa, Poland, 02-781
Contact: Site 0059         
Spain
Local Institution Not yet recruiting
Barcelona, Spain, 08035
Contact: Site 0047         
Local Institution Not yet recruiting
Madrid, Spain, 28041
Contact: Site 0046         
Local Institution Not yet recruiting
Madrid, Spain, 28009
Contact: Site 0045         
Local Institution Not yet recruiting
Pamplona, Spain, 31008
Contact: Site 0070         
Switzerland
Local Institution Recruiting
Lausanne, Switzerland, BT 02252
Contact: Site 0039         
Local Institution Recruiting
Zuerich, Switzerland, 8091
Contact: Site 0040         
United Kingdom
Local Institution Not yet recruiting
London, Greater London, United Kingdom, NW1 2PG
Contact: Site 0018         
Local Institution Not yet recruiting
Manchester, Greater Manchester, United Kingdom, M20 4BX
Contact: Site 0015         
Local Institution Not yet 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: October 13, 2014
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
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014