Clinical trial NCT03130959: A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies
Official title: Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Various Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-04-27
Enrollment: 166
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.


Eligibility criteria: Inclusion Criteria:

* Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
* A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy
* A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT
* A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy
* A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT
* A histologically-confirmed high grade CNS malignancy "other than above" which is recurrent or progressive after at least one line of prior therapy
* Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for \> 16 years of age assessed within two weeks of enrollment must be \>= 60
* A tumor sample must be available for submission to central laboratory (not required for DIPG)

Exclusion Criteria:

* An active, known, or suspected autoimmune disease
* A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
* Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs)
timeFrame: up to 6 weeks post-dosing
measure: Number of Safety Lead-In Participants With Serious Adverse Events (SAEs)
timeFrame: up to 6 weeks post-dosing
measure: Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose to 30 days post-last dose (up to approximately 6 weeks)
measure: Overall Survival (OS), Cohort 1 Only
timeFrame: up to approximately 42 months
measure: Progression-Free Survival (PFS), Cohorts 2-4
timeFrame: up to approximately 42 months
measure: Progression-Free Survival (PFS), Cohort 5 Only
timeFrame: up to approximately 42 months
Secondary outcomes:
measure: Progression-Free Survival (PFS), Cohort 1 Only
timeFrame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
measure: Overall Survival at 12 Months (OS12), Cohorts 1-4
timeFrame: From first dose to up to 12 months after first dose
measure: Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5
timeFrame: From first dose to up to 6 months after first dose
measure: Overall Survival (OS), Cohorts 2-5
timeFrame: From first dose to the date of death (up to approximately 55 months)
measure: Number of Treated Participants With Adverse Events (AEs)
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
measure: Number of Treated Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
measure: Number of Treated Participants With Drug-Related Adverse Events
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
measure: Number of Treated Participants With Adverse Events Leading to Discontinuation
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
measure: Number of Treated Participant Deaths
timeFrame: From first dose to the date of death (up to approximately 55 months)
measure: Number of Treated Participant With Laboratory Abnormalities - Liver
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
measure: Number of Treated Participant With Laboratory Abnormalities - Thyroid
timeFrame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0057
state: California
city: Aurora
country: United States
facility: Local Institution - 0016
state: Colorado
city: Gainesville
country: United States
facility: Local Institution - 0046
state: Florida
city: Chicago
country: United States
facility: Local Institution - 0011
state: Illinois
city: Baltimore
country: United States
facility: Local Institution - 0005
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0043
state: Massachusetts
city: Saint Louis
country: United States
facility: Local Institution - 0044
state: Missouri
city: New York
country: United States
facility: Local Institution - 0004
state: New York
city: New York
country: United States
facility: Local Institution - 0017
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Local Institution - 0066
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution
state: South Carolina
city: Memphis
country: United States
facility: Local Institution - 0012
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 0042
state: Texas
city: Randwick
country: Australia
facility: Local Institution - 0022
state: New South Wales
city: Sth Brisbane
country: Australia
facility: Local Institution - 0035
state: Queensland
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Parkville
country: Australia
facility: Local Institution - 0034
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0033
state: Western Australia
city: Porto Alegre
country: Brazil
facility: Local Institution - 0052
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Local Institution - 0051
state: Sao Paulo
city: Ribeirao Preto
country: Brazil
facility: Local Institution - 0053
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution - 0049
city: Sao Paulo
country: Brazil
facility: Local Institution - 0050
city: Toronto
country: Canada
facility: Local Institution - 0021
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0001
state: Quebec
city: Quebec
country: Canada
facility: Local Institution - 0002
city: Angers
country: France
facility: Local Institution - 0028
city: Bordeaux Cedex
country: France
facility: Local Institution - 0029
city: Lille
country: France
facility: Local Institution - 0027
city: Lyon
country: France
facility: Local Institution - 0025
city: Marseille
country: France
facility: Local Institution - 0024
city: Paris
country: France
facility: Local Institution - 0023
city: Vandoeuvre les Nancy
country: France
facility: Local Institution - 0064
city: VIillejuif
country: France
facility: Local Institution - 0026
city: Essen
country: Germany
facility: Local Institution - 0060
city: Hamburg
country: Germany
facility: Local Institution - 0061
city: Heidelberg
country: Germany
facility: Local Institution - 0063
city: Wuerzburg
country: Germany
facility: Local Institution - 0062
city: Hong Kong
country: Hong Kong
facility: Local Institution - 0018
city: Haifa
country: Israel
facility: Local Institution - 0059
city: Ramat Gan
country: Israel
facility: Local Institution - 0058
city: Rotterdam
country: Netherlands
facility: Local Institution - 0007
city: Utrecht
country: Netherlands
facility: Local Institution - 0008
city: Oslo
country: Norway
facility: Local Institution - 0067
city: Warszawa
country: Poland
facility: Local Institution - 0047
city: Moscow
country: Russian Federation
facility: Local Institution - 0048
city: Esplugues de Llobregat
country: Spain
facility: Local Institution - 0037
city: Madrid
country: Spain
facility: Local Institution - 0038
city: Valencia
country: Spain
facility: Local Institution - 0036
city: Solna
country: Sweden
facility: Local Institution - 0065
city: London
country: United Kingdom
facility: Local Institution - 0010
state: Greater London
city: Liverpool
country: United Kingdom
facility: Local Institution - 0013
state: Merseyside
city: Newcastle Upon Tyne
country: United Kingdom
facility: Local Institution - 0015
state: Tyne And Wear
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: