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 (CheckMate 908)
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| ClinicalTrials.gov Identifier: NCT03130959 |
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Recruitment Status :
Completed
First Posted : April 27, 2017
Results First Posted : April 1, 2021
Last Update Posted : August 9, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Various Advanced Cancer | Biological: Nivolumab Biological: Ipilimumab | Phase 2 |
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 166 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | June 12, 2017 |
| Actual Primary Completion Date : | March 10, 2020 |
| Actual Study Completion Date : | January 17, 2022 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Module A |
Biological: Nivolumab
Specified dose on specified days
Other Name: Opdivo, BMS-936558 |
| Experimental: Module B |
Biological: Nivolumab
Specified dose on specified days
Other Name: Opdivo, BMS-936558 Biological: Ipilimumab Specified dose on specified days
Other Name: Yervoy, BMS-734016 |
- Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: up to 6 weeks post-dosing ]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).
- Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) [ Time Frame: up to 6 weeks post-dosing ]The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.
- Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation [ Time Frame: From first dose to 30 days post-last dose (up to approximately 6 weeks) ]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.
- Overall Survival (OS), Cohort 1 Only [ Time Frame: up to approximately 42 months ]Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.
- Progression-Free Survival (PFS), Cohorts 2-4 [ Time Frame: up to approximately 42 months ]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-Free Survival (PFS), Cohort 5 Only [ Time Frame: up to approximately 42 months ]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-Free Survival (PFS), Cohort 1 Only [ Time Frame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months) ]
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
- Overall Survival at 12 Months (OS12), Cohorts 1-4 [ Time Frame: From first dose to up to 12 months after first dose ]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.
- Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 [ Time Frame: From first dose to up to 6 months after first dose ]
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
- Overall Survival (OS), Cohorts 2-5 [ Time Frame: From first dose to the date of death (up to approximately 55 months) ]Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.
- Number of Treated Participants With Adverse Events (AEs) [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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.
- Number of Treated Participants With Serious Adverse Events (SAEs) [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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.
- Number of Treated Participants With Drug-Related Adverse Events [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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.
- Number of Treated Participants With Adverse Events Leading to Discontinuation [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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.
- Number of Treated Participant Deaths [ Time Frame: From first dose to the date of death (up to approximately 55 months) ]The number of treated participants who died during the course of the study.
- Number of Treated Participant With Laboratory Abnormalities - Liver [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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)
- Number of Treated Participant With Laboratory Abnormalities - Thyroid [ Time Frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) ]
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)
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 6 Months to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03130959
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| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT03130959 |
| Other Study ID Numbers: |
CA209-908 2016-004441-82 ( EudraCT Number ) |
| First Posted: | April 27, 2017 Key Record Dates |
| Results First Posted: | April 1, 2021 |
| Last Update Posted: | August 9, 2022 |
| Last Verified: | July 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Neoplasms Nivolumab Ipilimumab Antineoplastic Agents, Immunological |
Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |