A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors

NCT06357377 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NEO100-03
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Pediatric Tumor of CNS; Pediatric Tumor of Brain; Pediatric Tumor of Brain Stem; Pineocytoma; Choroid Plexus Carcinoma, Childhood; Spinal Cord Tumor; High Grade Glioma; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

High grade glioma; Diffuse Midline Glioma; H3 K27-altered; Diffuse hemispheric glioma; H3 G34-mutant; Diffuse pediatric-type HGG; H3-wildtype; IDH-wildtype; spinal cord tumors; Brainstem; Posterior fossa; Choroid plexus carcinoma; CNS embryonal tumors; Pineoblastoma; NEO100

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (10)

• Identify the maximum tolerated dose (MTD) of NEO100

  6 months

• Determine the recommended Phase 2 dose (RP2D) of NEO100

  6 months

• Measurement of NEO100 and its metabolite perillic acid in brain tumor tissue

  6 months

• Blood brain barrier penetration

  6 months

• Characterize the pharmacokinetics (PK) of NEO100 as measured by Peak Plasma Concentration

  6 months

Study Arms (1)

Phase 1b safety, dose finding, brain-tumor delivery, and pharmacokinetics of IN NEO100

EXPERIMENTAL

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). The study will use a modified Fibonacci dose titration design, followed by a standard dose escalation design. * Cohort 1: 192 mg NEO100, QID on a 28-day cycle * Cohort 2: 288 mg NEO100, QID on a 28-day cycle * Cohort 3: 384 mg NEO100, TID on a 28-day cycle; * Cohort 4 (ceiling dose): 576 mg NEO100, BID on a 28-day cycle. Patients undergoing surgical or needle biopsy (only when clinically indicated) will receive a minimum of four days IN NEO100 treatment prior to the procedure.

Drug: NEO100

Interventions

NEO100 DRUG

NEO100 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.

Phase 1b safety, dose finding, brain-tumor delivery, and pharmacokinetics of IN NEO100

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Patients recurrent or progressive disease must have recovered from all acute side effects of prior therapy.
• From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
• Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg/m2 /dose continuously during radiation therapy for 42 days) or dexamethasone is allowed.
• Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.
• Surgical Resection: Patients may not have had a surgical resection within four weeks of starting NEO100 and any post-surgical complications must have resolved prior to initiation of NEO100.
• Radiation Therapy: Patients may not receive radiation therapy within four weeks of starting NEO100. Patients may not be enrolled if they require radiation therapy during Cycle 1 (the DLT Period). Patients may have SOC radiation therapy in Cycle 2 or beyond but will require a second DLT evaluation period to participate.
• Peripheral absolute neutrophil count (ANC) ≥ 1000/mm\^3 (1.0g/l) AND
• Platelet count ≥ 100,000/mm\^3 (100x10\^9/l) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m\^2.
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase (ALT)) ≤ 2 x ULN.

You may not qualify if:

• 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.
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds (ms).
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or the use of concomitant medications that prolong the QT/QTc interval.
• Participants with uncontrolled infection or other uncontrolled systemic illness.
• Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).
• Active illicit drug use or diagnosis of alcoholism.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.
• Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination as determined based upon available clinical details and not a study required MRI study or CSF test.
• Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.
• Concomitant use of potent CYP3A4/5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.
• Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids are allowed.

Sponsors & Collaborators

• Neonc Technologies, Inc.: lead

MeSH Terms

Conditions

Central Nervous System Neoplasms; Pinealoma; Choroid Plexus Carcinoma; Spinal Cord Neoplasms; Glioma

Interventions

perillyl alcohol

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Spinal Cord Diseases

Study Officials

• Thomas Chen, MD, PhD

  NeOnc Technologies Holdings, Inc.

  STUDY CHAIR

• Josh Neman, PhD

  NeOnc Technologies Holdings, Inc.

  STUDY DIRECTOR

Central Study Contacts

Chris Beardmore

CONTACT

(224) 218-2408; chris@anovaevidence.com

Chloe Richmond

CONTACT

(224) 218-2408; chloe@anovaevidence.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: April 10, 2024
• Study Start: January 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01