NEO100 and High-Grade Meningioma

An Open-Label, Phase 2 Study of NEO100 in Participants With Residual, Progressive or Recurrent High-Grade Meningioma

This multi-site, Phase 2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO100 (perillyl alcohol) for the treatment of patients with residual high-grade meningioma following resection surgery, radiographically-confirmed progression of high-grade meningioma or recurrent high-grade meningioma. There will be up to 30 patients enrolled in this study to have 29 evaluable patients. NEO100 will be self-administered four times daily on a 28-day treatment cycle for up to twelve cycles, until disease progression or death, whichever occurs first. Following the completion of cycle twelve, patients receiving benefit will be given the option to continue receiving compassionate use treatment with NEO100.

Study Overview

• Status: Recruiting
• Conditions: Residual, Progressive or Recurrent Grade II or III Meningioma
• Intervention / Treatment: Drug: NEO100

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chris Beardmore; Phone Number: 224 218 2408; Email: chris@anovaevidence.com
• Study Contact Backup: Name: Chloe Richmond; Phone Number: 224 218 2408; Email: chloe@anovaevidence.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
      • Contact: Aida Lozada, MA; Phone Number: 323-865-3980; Email: Aida.Lozada@med.usc.edu
      • Principal Investigator: Frances Chow, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patient must:

Have histologically confirmed WHO Grade II or III meningioma that is residual, progressive or recurrent following at least minimally safe resection and radiation therapy. Metastatic meningiomas are allowed.

• Residual disease is defined as residual measurable disease (without a requirement for progression). Residual measurable disease is defined by bidimensionally measurable lesions with clearly defined margins by MRI scan(s) with a minimum diameter of 10mm in both dimensions.
• Progressive disease is defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area). The change must occur between scans separated by no more than 24 months.
• Recurrent disease is defined as new evidence of measurable disease following complete resection (10mm in both dimensions).
• Be on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.
• Participants must have failed maximal safe resection and radiation therapy.

There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents, however, these treatment (s) must comply with the following:

• There is no limit on the number of prior therapies.
• Prior medical therapy is allowed but is not required.
• No chemotherapy, other investigational agents within 14 days of study treatment.
• For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas/alkylating agents) or biologic therapies.
• No other concurrent receipt of investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study.
• Patients may have been treated with standard external beam radiation or radiosurgery in any combination, however an interval of ≥12 weeks (84 days) must have elapsed from the completion of the radiation therapy to the initiation of study therapy unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line). In addition, there must be subsequent evidence of tumor progression after completion of radiation therapy;
• An interval of ≥ 28 days and full recovery (no ongoing safety issues) from surgical resection is required;
• Meningioma that have resulted from prior radiation therapy are allowed.
• There must be an interval of ≥ 7 days from stereotactic biopsy; and Participants must have recovered to grade ≤1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include but are not limited to alopecia, laboratory values listed per inclusion criteria and lymphopenia).

Patient must be ≥ 12 years of age. Patient must have an ECOG performance status of 0-2 or KPS ≥ 60. Patient must have an expected survival of at least three months. Patient must be willing to provide blood samples for pharmacokinetic study (to assess proper administration of NEO100).

Patient must have adequate organ and marrow function as defined below:

• White blood cell (WBC) ≥2000/microliter
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥9 gm/dl
• AST (SGOT)/ALT (SPGT) ≤ 2.5 × laboratory upper limit of normal (ULN)
• Serum creatinine ≤ 1.5 x laboratory upper limit of normal (ULN) or
• Creatinine clearance (meas or calc) ≥60mL/min for participants with creatinine levels >1.5x laboratory upper limit of normal (ULN)
• Total serum bilirubin ≤ 1.5 x laboratory upper limit of normal (ULN) except participants with Gilbert's Syndrome who can have a total serum bilirubin of <5 x laboratory upper limit of normal (ULN) MRI (or CT if MRI contraindicated) within 14 days prior to start of study drug. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening scan and the start of treatment, a new baseline scan is required.

Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first administration of study drug, for the duration of study participation, and for 90 days following completion of therapy. Should a female patient become pregnant, or suspect she is pregnant, while participating in this study, she should inform her treating physician immediately.

• A female of child-bearing potential is any woman (regardless of sexual orientation, not having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• A negative serum pregnancy test will be required of all female patients of child-bearing potential within seven days prior to initiating study drug.
• A serum pregnancy test will be repeated immediately if pregnancy is suspected. Women must not be breastfeeding. Patient must have the ability to understand, and the willingness to sign, a written informed consent.

Exclusion Criteria

If the patient meets any of the following criteria, the patient must not be enrolled:

Patients who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days (or 5 half-lives, whichever is shorter) of study treatment.

Patient has completed chemo-radiation within the last 84 days prior to the first administration of study drug, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression.

Patient has had surgery within seven days prior to the date of informed consent.

Patient has had cytotoxic chemotherapy within 4 weeks (or 5 half-lives, whichever is shorter), nitrosoureas/alkylating agents within 6 weeks or biologic therapies.

Prior treatment with interstitial brachytherapy within 6 months of start of study therapy.

Current or planned participation in a clinical trial of an investigational agent or using an investigational medical device.

The patients disease is primarily localized to the brainstem or spinal cord. Patient has not recovered from adverse events due to chemotherapy, immunotherapy, or radiation therapy.

Patient has had prior treatment with perillyl alcohol, administered either intravenously or intranasally.

Patient has a history of allergic reactions attributed to perillyl alcohol. Patient has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Patient has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Patient must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Patient has a history of new diagnosis or treatment of cancer other than meningioma within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.

Leptomeningeal involvement of the patient's tumor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with high-grade meningioma; 30 patients with residual high-grade meningioma following resection surgery, radiographically-confirmed progression of high-grade meningioma or recurrent high-grade meningioma	Drug: NEO100; NEO100 is a purified form of perillyl alcohol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival as six months (PFS6).	Progression free survival	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	12 months
Objective Tumor response to NEO100 as determined by RANO criteria	6 months
Perillic acid measurement	30 days

Collaborators and Investigators

• Sponsor: Neonc Technologies, Inc.
• Investigators: Study Chair: Tom Chen, MD, PhD, NeOnc Technologies; Study Director: Vincent F Simmon, PhD, NeOnc Technologies; Study Director: Patrick Walters, NeOnc Technologies

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Residual, Progressive or Recurrent Grade II or III Meningioma
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Disease Attributes; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Recurrence; Meningioma
• Other Study ID Numbers: NEO100-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No