Andrew P. Groves
This is a single-arm open-label phase 1 dose escalation/expansion trial assessing the safety and efficacy of concurrent intrathecal azacitidine and intrathecal nivolumab in recurrent high-grade glioma.
PRIMARY OUTCOME Phase I To determine the safety and maximum tolerated dose (MTD) of intrathecal (IT) azacitidine in combination with IT nivolumab in patients with recurrent high-grade glioma Expansion Cohort To estimate the overall response rate (ORR) SECONDARY OUTCOMES To estimate: 1. Duration of response (DOR) 2. Progression-free survival (PFS) 3. Overall survival (OS) EXPLORATORY OUTCOMES Changes in immune profiling (flow cytometry, cytokine/chemokine analysis) and circulating tumor DNA (ctDNA) biomarkers (quantification, DNA methylation)
INCLUSION CRITERIA 1. For patients age ≥ 18: Able and willing to provide written informed consent 2. For patients aged 13-17: Parent/guardian of adolescent patient must have the ability to provide written informed consent. Adolescent patients must have the ability to provide written informed assent. 3. Stated willingness to comply with all trial procedures and availability for the duration of the trial 4. Histologically confirmed diagnosis of World Health Organization Grade IV high-grade glioma. Eligible diagnoses include: Glioblastoma (IDH-wildtype), Gliosarcoma, Diffuse Midline Glioma (H3 K…
Intrathecal nivolumab will be given at a flat dose of 40 mg
Intrathecal azacitidine will be dose-escalated with 4 dose levels (5, 10, 20, 40 mg) using a 3+3 design.
Lumbar puncture for intrathecal delivery and collection of CSF
MRI Brain and full Spine (with and without contrast) will be performed prior to enrollment. During trial therapy, MRI Brain (with and without contrast) will be performed after cycle 1 and after that every 8 weeks (e.g. after cycle 3, cycle 5, etc…)
Arctuva estimate
Actual pay is set by the research site.
Verify or correct the compensation shown for this listing.