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

Various Advanced Cancer Clinical Trial

— CheckMate 908  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03130959
• Other study ID #: CA209-908
• Secondary ID: 2016-004441-82
• Status: Completed
• Phase: Phase 2
• Start date: June 12, 2017
• Est. completion date: January 17, 2022

Study information

• Verified date: July 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: January 17, 2022
• Est. primary completion date: March 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Various Advanced Cancer

Intervention

Biological:
• Nivolumab
Specified dose on specified days
• Ipilimumab
Specified dose on specified days

Locations

Country	Name	City	State
Australia	Local Institution	Clayton	Victoria
Australia	Local Institution - 0033	Nedlands	Western Australia
Australia	Local Institution - 0034	Parkville	Victoria
Australia	Local Institution - 0022	Randwick	New South Wales
Australia	Local Institution - 0035	Sth Brisbane	Queensland
Brazil	Local Institution - 0051	Barretos	Sao Paulo
Brazil	Local Institution - 0052	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0053	Ribeirao Preto	Sao Paulo
Brazil	Local Institution - 0049	Sao Paulo
Brazil	Local Institution - 0050	Sao Paulo
Canada	Local Institution - 0001	Montreal	Quebec
Canada	Local Institution - 0002	Quebec
Canada	Local Institution - 0021	Toronto	Ontario
France	Local Institution - 0028	Angers
France	Local Institution - 0029	Bordeaux Cedex
France	Local Institution - 0027	Lille
France	Local Institution - 0025	Lyon
France	Local Institution - 0024	Marseille
France	Local Institution - 0023	Paris
France	Local Institution - 0064	Vandoeuvre les Nancy
France	Local Institution - 0026	VIillejuif
Germany	Local Institution - 0060	Essen
Germany	Local Institution - 0061	Hamburg
Germany	Local Institution - 0063	Heidelberg
Germany	Local Institution - 0062	Wuerzburg
Hong Kong	Local Institution - 0018	Hong Kong
Israel	Local Institution - 0059	Haifa
Israel	Local Institution - 0058	Ramat Gan
Netherlands	Local Institution - 0007	Rotterdam
Netherlands	Local Institution - 0008	Utrecht
Norway	Local Institution - 0067	Oslo
Poland	Local Institution - 0047	Warszawa
Russian Federation	Local Institution - 0048	Moscow
Spain	Local Institution - 0037	Esplugues de Llobregat
Spain	Local Institution - 0038	Madrid
Spain	Local Institution - 0036	Valencia
Sweden	Local Institution - 0065	Solna
United Kingdom	Local Institution - 0013	Liverpool	Merseyside
United Kingdom	Local Institution - 0010	London	Greater London
United Kingdom	Local Institution - 0015	Newcastle Upon Tyne	Tyne And Wear
United States	Local Institution - 0016	Aurora	Colorado
United States	Local Institution - 0005	Baltimore	Maryland
United States	Local Institution - 0043	Boston	Massachusetts
United States	Local Institution	Charleston	South Carolina
United States	Local Institution - 0011	Chicago	Illinois
United States	Cincinnati Children'S Hospital Medical Center	Cincinnati	Ohio
United States	Local Institution - 0046	Gainesville	Florida
United States	Local Institution - 0042	Houston	Texas
United States	Local Institution - 0057	Los Angeles	California
United States	Local Institution - 0012	Memphis	Tennessee
United States	Local Institution - 0004	New York	New York
United States	Local Institution - 0017	New York	New York
United States	Local Institution - 0066	Philadelphia	Pennsylvania
United States	Local Institution - 0044	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Hong Kong,  Israel,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	up to 6 weeks post-dosing
Primary	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.	up to 6 weeks post-dosing
Primary	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.	From first dose to 30 days post-last dose (up to approximately 6 weeks)
Primary	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.	up to approximately 42 months
Primary	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.	up to approximately 42 months
Primary	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.	up to approximately 42 months
Secondary	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.; Progression is defined as: = 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement; Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor; Failure to return for evaluation as a result of death or deteriorating condition; Clear progression of non-measurable disease	From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
Secondary	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.	From first dose to up to 12 months after first dose
Secondary	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.; Progression is defined as: = 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement; Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor; Failure to return for evaluation as a result of death or deteriorating condition; Clear progression of non-measurable disease	From first dose to up to 6 months after first dose
Secondary	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.	From first dose to the date of death (up to approximately 55 months)
Secondary	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.; An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Secondary	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.; SAE is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening; Requires inpatient hospitalization or causes prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event; 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.	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Secondary	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.; An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Secondary	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.; An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Secondary	Number of Treated Participant Deaths	The number of treated participants who died during the course of the study.	From first dose to the date of death (up to approximately 55 months)
Secondary	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) Units per Liter (U/L) Results reported in International System of Units (SI)	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Secondary	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) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Milliunits per Liter (mlU/L) Results reported in International System of Units (SI)	From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting