This is open label, multicentre, single arm, pilot study of upfront nivolumab in patients with RRD-glioblastoma with favorable immune/genomic biomarkers. The purpose of the study is to use upfront immune checkpoint inhibitor (ICI) to delay/avoid radiation for patients with RRD-glioblastoma with favorable clinical (Gross total resection (GTR) or near total resection (NTR)) and biological (RRD, hypermutation, immune activation) biomarkers. At progression, patients will be undergoing surgery/biopsy and will get a combination of radiation + ICI followed by maintenance ICI. This model will allow us to additionally study the evolution tumor in response to ICI. The study will have two domains.
3.1.1 Age: Patients must be ≥12 months and ≤25 years of age at the time of signing informed consent/assent.
Cytotoxic chemotherapy: At least 21 days prior to initiation of protocol therapy from the last dose of cytotoxic or myelosuppressive chemotherapy; at least 42 days if prior nitrosourea (such as lomustine, CCNU).
Hematopoietic growth factors: At least 7 days prior to initiation of protocol therapy from the last dose of short-acting growth factor; at least 14 days for long-acting.
Anti-cancer agents not known to be myelosuppressive: At least 7 days prior to initiation of protocol therapy from the last dose.
3.2.1
Corticosteroids: Patients requiring systemic corticosteroids or other forms of immunosuppressive therapy within 7 days prior to initiation of protocol therapy are not eligible.
Following initiation of protocol therapy, systemic corticosteroids or other forms of immunosuppressive therapy are permitted if administered for the treatment of toxicity, tumor flare, or pseudo-progression and can be tapered. In most cases protocol therapy must be held until the dose is tapered to 10 mg/day prednisone or equivalent. The Protocol Principal Investigator must be consulted prior to resuming treatment.
Physiologic corticosteroids up to 5 mg/day prednisone or equivalent are permitted.
Single group
Nivolumab
DrugAll patients will be administered Nivolumab with or without radiation
Radiation
RadiationRadiation
To evaluate Radiation-free survival (RFS) from start of immunotherapy
Radiation-free survival defined as time from start of immunotherapy to date of onset of radiation for progression/recurrence as determined by the iRANO criteria.
To evaluate overall survival (OS)
Defined as the time from date of enrollment until death from any cause.
To evaluate progression free survival (post first progression)
Defined as time from first progression (post upfront ICI) to second progression as determined by the iRANO criteria.
To evaluate clinical benefit rate (CBR)
The proportion of patients who have no evidence of progression for at least two protocol reassessment periods as determined by the iRANO criteria.
Quality of life as measured by a validated PedsQL, generic module and PROMIS.
Patients and/or caregivers will complete questionnaires during regular clinic visits at three required time points: time of study enrollment, 12 weeks of therapy, end of study.
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Daniel Morgenstern
Lead sponsor
The Hospital for Sick Children
Sponsor institution
Canadian Institutes of Health Research (CIHR)
Collaborator
Anti Cancer Fund
Collaborator
