A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients - Full Text View

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:

Drug Information available for: Bevacizumab Ipilimumab Nivolumab

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

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:	April 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

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 60 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site


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 23, 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 September 27, 2016

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