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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03130959




Registration number
NCT03130959
Ethics application status
Date submitted
5/04/2017
Date registered
27/04/2017
Date last updated
1/04/2021

Titles & IDs
Public title
An Investigational Immuno-therapy Study of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Patients With High Grade Primary CNS Malignancies
Scientific title
Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies
Secondary ID [1] 0 0
2016-004441-82
Secondary ID [2] 0 0
CA209-908
Universal Trial Number (UTN)
Trial acronym
CheckMate 908
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Various Advanced Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Nivolumab
Other interventions - Ipilimumab

Experimental: Module A - nivolumab

Experimental: Module B - nivolumab plus ipilimumab


Other interventions: Nivolumab
Specified dose on specified day

Other interventions: Ipilimumab
Specified dose on specified day

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) - A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed > 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).
Timepoint [1] 0 0
up to 6 weeks post-dosing
Primary outcome [2] 0 0
Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) - The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.
Timepoint [2] 0 0
up to 6 weeks post-dosing
Primary outcome [3] 0 0
Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation - The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.
Timepoint [3] 0 0
up to 6 weeks post-dosing
Primary outcome [4] 0 0
Overall Survival (OS), Cohort 1 Only - Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.
Timepoint [4] 0 0
up to approximately 42 months
Primary outcome [5] 0 0
Progression-Free Survival (PFS), Cohorts 2-4 - Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Timepoint [5] 0 0
up to approximately 42 months
Primary outcome [6] 0 0
Progression-Free Survival (PFS), Cohort 5 Only - Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Timepoint [6] 0 0
up to approximately 42 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS), Cohort 1 Only - Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Timepoint [1] 0 0
up to approximately 42 months
Secondary outcome [2] 0 0
Overall Survival at 12 Months (OS12), Cohorts 1-4 - Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability.
Timepoint [2] 0 0
up to 12 months
Secondary outcome [3] 0 0
Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 - Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free.
Timepoint [3] 0 0
up to 6 months
Secondary outcome [4] 0 0
Overall Survival (OS), Cohorts 2-5 - Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.
Timepoint [4] 0 0
up to approximately 42 months
Secondary outcome [5] 0 0
Number of Treated Participants With Adverse Events (AEs) - The number of treated participants who experienced an Adverse Event (AE) during the course of the study.
Timepoint [5] 0 0
from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [6] 0 0
Number of Treated Participants With Serious Adverse Events (SAEs) - The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study.
Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.
Timepoint [6] 0 0
from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [7] 0 0
Number of Treated Participants With Drug-Related Adverse Events - The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study.
Timepoint [7] 0 0
from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [8] 0 0
Number of Treated Participants With Adverse Events Leading to Discontinuation - The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study.
Timepoint [8] 0 0
from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [9] 0 0
Number of Treated Participant Deaths - The number of treated participants who died during the course of the study.
Timepoint [9] 0 0
from first dose assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [10] 0 0
Number of Treated Participant With Laboratory Abnormalities - Liver - The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study.
Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
Timepoint [10] 0 0
from first dose assessed up to 13Jan2021 (up to approximately 42 months)
Secondary outcome [11] 0 0
Number of Treated Participant With Laboratory Abnormalities - Thyroid - The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study.
Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Timepoint [11] 0 0
from first dose assessed up to 13Jan2021 (up to approximately 42 months)

Eligibility
Key inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please
visit www.BMSStudyConnect.com

- Children and adolescents diagnosed with either:

- Diffuse Intrinsic Pontine Glioma (DIPG), in first-line, after completion of standard
radiotherapy

- High Grade Glioma (HGG), recurrent or progressive

- Medulloblastoma, recurrent or progressive

- Ependymoma, recurrent or progressive

- Other high-grade tumors of the central nervous system, recurrent or progressive

- 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]
Minimum age
6 Months
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants with active, known or suspected autoimmune disease

- Participants unable to taper steroids due to ongoing mass effect

- Participants with low-grade gliomas or tumors of unknown malignant potential

- Prior treatment with any drug that targets T cell co-stimulation pathways (such as
checkpoint inhibitors)

Other protocol defined inclusion/exclusion criteria could apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Randwick
Recruitment hospital [2] 0 0
Local Institution - Sth Brisbane
Recruitment hospital [3] 0 0
Local Institution - Clayton
Recruitment hospital [4] 0 0
Local Institution - Parkville
Recruitment hospital [5] 0 0
Local Institution - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - Sth Brisbane
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3052 - Parkville
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Brazil
State/province [14] 0 0
RIO Grande DO SUL
Country [15] 0 0
Brazil
State/province [15] 0 0
Sao Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Angers
Country [19] 0 0
France
State/province [19] 0 0
Bordeaux Cedex
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Vandoeuvre les Nancy
Country [25] 0 0
France
State/province [25] 0 0
VIillejuif
Country [26] 0 0
Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Hamburg
Country [28] 0 0
Germany
State/province [28] 0 0
Heidelberg
Country [29] 0 0
Germany
State/province [29] 0 0
Wuerzburg
Country [30] 0 0
Hong Kong
State/province [30] 0 0
Hong Kong
Country [31] 0 0
Israel
State/province [31] 0 0
Haifa
Country [32] 0 0
Israel
State/province [32] 0 0
Ramat Gan
Country [33] 0 0
Netherlands
State/province [33] 0 0
Rotterdam
Country [34] 0 0
Netherlands
State/province [34] 0 0
Utrecht
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Poland
State/province [36] 0 0
Warszawa
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Moscow
Country [38] 0 0
Spain
State/province [38] 0 0
Esplugues de Llobregat
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Sweden
State/province [41] 0 0
Solna
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Greater London
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Merseyside
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Tyne And Wear

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT03130959
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications