Brain Cancer CNS Malignancies
Conditions
Interventions
Treatments are defined by Module:
Module A: nivolumab 3 mg/kg every 2 weeks, as monotherapy, and
Module B: nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, every 3 weeks for 4 doses
followed by nivolumab 3
Sponsors
Bristol-Myers Squibb
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Prior to study participation, written informed consent from participants, or in the case of minors, written permission (informed consent) from parents or legally acceptable representatives. • Males and Females, ages >= 6 months to 16 years of age must be >= 60. • Women of child-bearing potential must have a negative pregnancy test within 24 hours of starting treatment, and should not be breastfeeding. Women of childbearing potential, or male subjects who are sexually active with women of child-bearing potential must agree to the contraceptive requirements of the study.
Exclusion criteria
Exclusion criteria: • Participants with active, known, or suspected autoimmune disease. • Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. • Participants who cannot undergo magnetic resonance imaging (MRI) with contrast enhancement. • Specific blood test results indicating impaired haematological, liver or kidney function • Participants cannot test positive for Hepatitis B/C • Participants must not have HIV or AIDs • Unable to taper steroids due to ongoing mass effect • Participants with low-grade gliomas or tumors of unknown malignant potential • Evidence of > Grade 1 recent CNS hemorrhage on the baseline MRI scan. • Participants with bulky tumor on imaging are ineligible; bulky tumor is defined as: i) Tumor with any evidence of uncal herniation or severe midline shift ii) Tumor with diameter of > 6 cm in one dimension on contrast-enhanced MRI iii) Tumor that in the opinion of the investigator, shows significant mass effect. • Prior treatment with any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. • Prior allogeneic hematopoietic cell transplantation (unless MM approval in advance). • Participants who are receiving any other anti-cancer or investigational drug therapy or non-palliative radiation therapy. • Any serious or uncontrolled medical disorder that may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results. • Patients cannot be incarcerated or detained for a psychiatric or physical illness • History of allergy or hypersensitivity to study drug components or to any monoclonal antibody.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For safety lead in: To estimate the safety and tolerability of study treatments (firstly nivolumab alone, and then nivolumab in combination with ipilimumab) in pediatric participants with primary high- grade CNS tumors. For expansion: To investigate efficacy of the study treatments (as assessed by Overall Survival and Progressive Free survival), individually in each of pediatric cohorts, as follows: Cohort 1: OS in newly diagnosed DIPG Cohort 2: PFS in recurrent or progressive HGG Cohort 3: PFS in Progressive medulloblastoma Cohort 4: PFS in Recurrent or progressive ependymoma Cohort 5: PFS in Recurrent or progressive other rare CNS tumors (including pineoblastoma, AT/RT, embryonic CNS tumors) | — |
Secondary
| Measure | Time frame |
|---|---|
| To describe any observed anti-tumor activity of study treatment in pediatric primary high grade CNS tumors. To estimate the safety of study therapy in all cohorts by incidence of laboratory abnormalities, AEs, SAEs, drug-related AEs, AEs leading to discontinuation, and death. To further characterise the efficacy of the study treatment in each cohort by rates of progression free survival at 6 months and overall survival at 12 months. | — |
Countries
Netherlands
Outcome results
None listed