NEO100 and High-Grade Meningioma

Study Overview
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Brief Summary
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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.

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

Conditions
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Residual, Progressive or Recurrent Grade II or III Meningioma

Intervention / Treatment
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* Drug: NEO100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Patients' tumor must not be >30 mm (length x width) and must not be multifocal 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 sample for pharmacokinetic study (to assess proper administration of NEO100). Patient must have adequate organ and marrow function. 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. Women must not be breastfeeding. Patient must have the ability to understand, and the willingness comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study as confirmed by signing a written informed consent document. Exclusion Criteria: 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 patient's 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. 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 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 high-grade 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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor response to NEO100 as determined by RANO criteria |  | 6 months | 
| Overall survival |  | 12 months | 
| Perillic acid measurement |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Residual, Progressive or Recurrent Grade II or III Meningioma