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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Recurrent Glioblastoma	Biological: Nivolumab; Biological: Bevacizumab; Biological: Ipilimumab	Phase 3

Detailed Description:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	626 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Actual Study Start Date :	January 27, 2014
Actual Primary Completion Date :	January 10, 2017
Estimated Study Completion Date :	October 26, 2018

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
2. Cohort 2: Overall Survival (OS) [ Time Frame: Approximately 36 months ]

   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 :

1. Cohort 2: Overall Survival rate (OS) [ Time Frame: Approximately 36 months ]
   Comparing OS between Nivolumab and Bevacizumab
2. Cohort 2: Progression Free Survival (PFS) [ Time Frame: Approximately 36 months ]

   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

3. Cohort 2: Objective Response Rate(ORR) [ Time Frame: Approximately 36 months ]

   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

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
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

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  Show 60 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

BMS Clinical Trial Information 

FDA Safety Alerts and Recalls 

BMS Clinical Trial Patient Recruiting 

Investigator Inquiry Form 

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02017717 History of Changes
Other Study ID Numbers:	CA209-143; 2013-003738-34 ( EudraCT Number )
First Posted:	December 23, 2013
Last Update Posted:	March 16, 2018
Last Verified:	March 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

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