This is an open label, Phase 1b safety, dose-finding, brain tumor delivery, and pharmacokinetics study of intranasal NEO100 in patients with pediatric-type diffuse high grade gliomas. Patients will receive IN NEO100 that will follow a dose titration design, followed by a standard dose escalation design to establish safety. Brain tumor delivery of NEO100 will be confirmed in each disease sub-type by surgical resection/needle biopsy only if clinically indicated and scheduled for clinical purposes and testing with residual tissue for NEO100 and the major metabolite of NEO100 (Perillic Acid).
Patient must have radiographically confirmed, newly diagnosed or recurrent pediatric-type high grade glioma: Diffuse Midline Glioma, H3 K27-altered; Diffuse hemispheric glioma, H3 G34-mutant, Diffuse pediatric-type HGG, grade III and IV H3-wildtype and IDH-wildtype with imaging and/or pathology consistent with a DMG, (including spinal cord tumors); or Recurrent malignant tumors involving the brainstem or posterior fossa (choroid plexus carcinoma, CNS embryonal tumors, and pineoblastoma).
Karnofsky ≥ 50 for patients > 16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
If clinically indicated, participants must be willing to provide adequate tissue for PK analysis, either from a surgical biopsy or needle biopsy.
Aged ≥5 to ≤18 years.
Diagnosis of any pediatric-type glioma not described in inclusion criteria.
Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy/resection should be discussed with the Medical Monitors.
Participants who are currently receiving other anti-cancer agents.
Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the Medical Monitor.
Single group
NEO100
DrugNEO100 is a purified form (\>98.5%) of the naturally occurring monoterpene perillyl alcohol. NEO100 drug product is a non-sterile solution for intranasal administration. It is compounded as a 10% solution in a 50:50 mixture of ethanol:glycerol.
Nature and severity of adverse events
Assess the safety and tolerability of increasing dose levels of intranasally administered NEO100 using the NCI CTCAE (version 5.0) for reporting of non-hematologic AEs
Identify the maximum tolerated dose (MTD) of NEO100
Assess the maximum tolerated dose (MTD) of intranasally administered NEO100 using the NCI CTCAE (version 5.0) for reporting of non-hematologic AEs
Determine the recommended Phase 2 dose (RP2D) of NEO100
Assess the maximum tolerated dose (MTD) of intranasally administered NEO100 using the NCI CTCAE (version 5.0) for reporting of non-hematologic AEs
Measurement of NEO100 and its metabolite perillic acid in brain tumor tissue
Confirm brain tumor delivery by measuring levels of NEO100 (POH) and its metabolite perillic acid (PA) in postsurgical tumor tissue in patients with pediatric-type brain tumors (measured in ng/mg).
Blood brain barrier penetration
To confirm blood brain barrier (BBB) penetration of NEO100 by measuring the concentration of NEO100 and its metabolite in resected tumor tissue.
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