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: September 16, 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: June 2017
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 #.

  Show 37 Study Locations
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: September 16, 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 September 18, 2014