NEO100 for Meningioma

Overseen By Frances E. Chow

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Neonc Technologies, Inc.

Must not be taking: Chemotherapy, Investigational agents

Disqualifiers: Pregnancy, Breastfeeding, Inadequate organ function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

30 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take chemotherapy or investigational agents within 14 days of starting the study treatment. For prior systemic agents, you must wait at least 4 weeks (or 5 half-lives, whichever is shorter) before starting the trial. No concurrent investigational agents or meningioma-directed therapy is allowed during the study.

What data supports the idea that NEO100 for Meningioma is an effective treatment?

The available research does not provide direct evidence that NEO100 is effective for treating Meningioma. Most of the studies focus on its use for glioblastoma, a different type of brain tumor. For instance, clinical trials in Brazil suggested that NEO100 might help patients with recurrent glioblastoma when given through the nose. Another study showed that NEO100 could reduce tumor growth and increase survival in animals with gliomas, a type of brain cancer. However, there is no specific data on its effectiveness for Meningioma. ^{1 2 3 4 5}

What safety data exists for NEO100 treatment?

NEO100, a highly purified version of perillyl alcohol (POH), has been evaluated for safety in several studies. Oral administration of POH was previously abandoned due to intolerable side effects like nausea, fatigue, and vomiting. However, intranasal delivery has shown promise, with clinical trials in Brazil indicating it is well tolerated and effective for treating recurrent malignant gliomas. A Phase I/IIa clinical trial in the United States is also evaluating the safety and efficacy of intranasal NEO100 for glioblastoma. Preclinical studies in rats have demonstrated improved bioavailability and tolerability of POH when delivered intranasally using a nanoemulsion. ^{3 4 6 7 8}

Is the drug NEO100 a promising treatment for meningioma?

NEO100, a purified form of perillyl alcohol, shows promise as a treatment because it can cross the blood-brain barrier, which is a major challenge in treating brain-related conditions. It has been tested in clinical trials for brain cancers like glioblastoma, with encouraging results, especially when delivered intranasally. This suggests it could be effective for other brain tumors, such as meningioma. ^{3 4 6 9 10}

What is the purpose of this trial?

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 until disease progression, death or patient withdraw from study for any reason, whichever occurs first.

Research Team

Vincent F Simmon, PhD

Principal Investigator

NeOnc Technologies

Patrick Walters

Principal Investigator

NeOnc Technologies

Tom Chen, MD, PhD

Principal Investigator

NeOnc Technologies

Eligibility Criteria

This trial is for patients with high-grade meningioma that's come back or hasn't fully been removed by surgery. They should have a life expectancy of at least three months, be over 12 years old, and not have tumors larger than 30 mm or in multiple places. Participants need to be stable on steroids for five days before consent and agree to use contraception. Those who've had certain recent treatments or uncontrolled illnesses can't join.

Inclusion Criteria

Patient must have an expected survival of at least three months.

My meningioma is Grade II or III and has come back or gotten worse after surgery and radiation.

My organs and bone marrow are working well.

Exclusion Criteria

I have been treated with perillyl alcohol before.

I had a specific radiation treatment called brachytherapy less than 6 months ago.

My cancer has spread to the lining of my brain and spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants self-administer NEO100 intranasally four times daily on a 28-day treatment cycle until disease progression, death, or withdrawal

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• NEO100

Trial Overview The study tests NEO100 (perillyl alcohol) given four times daily over a 28-day cycle, up to twelve cycles unless the disease progresses or the patient passes away. Up to thirty patients will take part, aiming for twenty-nine evaluable participants. The trial checks how safe NEO100 is, how it moves through the body (pharmacokinetics), and its effectiveness against residual or recurring high-grade meningioma.

Participant Groups

Group I: Patients with high-grade meningioma Experimental Treatment 1 Intervention

30 patients with residual high-grade meningioma following resection surgery, radiographically-confirmed progression of high-grade meningioma or recurrent high-grade meningioma

NEO100 is already approved in United States for the following indications:

Approved in United States as NEO100 for:

• High-grade meningioma
• Recurrent glioblastoma

Who Is Running the Clinical Trial?

Neonc Technologies, Inc.

Lead Sponsor

Trials

4

Recruited

230+

Findings from Research

Perillyl alcohol (POH) is effective against both temozolomide-sensitive and temozolomide-resistant glioma cells, showing cytotoxic effects through mechanisms involving endoplasmic reticulum stress and inhibition of survival pathways.

Intranasal administration of POH was well tolerated and led to decreased tumor growth and increased survival in animal models with intracranial tumors, suggesting a promising route for treatment of resistant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perillyl alcohol for the treatment of temozolomide-resistant gliomas. Cho, HY., Wang, W., Jhaveri, N., et al.[2021]

Perillyl alcohol (POH) effectively inhibits the growth of both estrogen receptor-positive and negative breast cancer cell lines in a dose-dependent manner, primarily by causing cell cycle arrest in the G1 phase.

In a mouse model, POH significantly suppressed tumor growth and lymph node metastasis when administered at a dose of 75 mg/kg three times a week over a 6-week period, demonstrating its potential as a therapeutic agent against breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo. Yuri, T., Danbara, N., Tsujita-Kyutoku, M., et al.[2016]

Intranasal delivery of NEO100, a pharmaceutical-grade version of perillyl alcohol, successfully resulted in the detection of both perillyl alcohol and its metabolite perillic acid in a patient's glioblastoma tumor tissue after over 3 years of treatment.

This study is the first to demonstrate that intranasal administration can effectively deliver therapeutic agents to brain tumors, suggesting that this noninvasive method could be a promising new treatment option for glioblastoma and potentially other brain-localized malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of perillyl alcohol and its metabolite perillic acid in postsurgical glioblastoma tissue after intranasal administration of NEO100: illustrative case. Schönthal, AH., Swenson, S., Bonney, PA., et al.[2022]

Intranasal delivery of NEO100, a purified form of perillyl alcohol, was well tolerated in a Phase I trial with 12 patients suffering from recurrent glioblastoma, with no severe adverse events reported.

The treatment showed promising survival outcomes, with a 33% progression-free survival at 6 months and a 55% overall survival at 12 months, suggesting that this novel approach may be beneficial for patients with recurrent GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. Schönthal, AH., Peereboom, DM., Wagle, N., et al.[2022]

In a study of 67 patients with recurrent malignant gliomas treated with intranasal perillyl alcohol, those with tumors located in the basal ganglia had significantly longer survival compared to those with lobar gliomas.

The presence of peritumoral brain edema (PTBE) was associated with poor therapeutic response and shorter survival, indicating that tumor size and edema may influence treatment outcomes and the behavior of glioma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol. Da Fonseca, CO., Silva, JT., Lins, IR., et al.[2021]

S-(-)-Perillyl alcohol was successfully converted into a new metabolite, 1,2-dihydroxyperillyl alcohol, by the fungus Fusarium heterosporium over a 10-day period, indicating potential for biotransformation in drug development.

The conversion yielded 13% of the new metabolite, which was characterized using various spectroscopic methods, suggesting that this process could be useful for producing novel compounds with possible therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbial hydroxylation of S-(-)-perillyl alcohol by Fusarium heterosporium. Kiran, I.[2016]

Perillyl alcohol (POH), a natural compound, initially showed promise in inhibiting tumor growth in preclinical studies, but clinical trials using oral administration resulted in significant side effects like nausea and vomiting, leading to patient withdrawals.

Recent trials in Brazil using intranasal delivery of POH for patients with recurrent malignant gliomas demonstrated that this method is well tolerated and effective, reviving interest in POH as a potential cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy. Chen, TC., Fonseca, CO., Schönthal, AH.[2022]

Perillyl alcohol (POH) shows strong antitumor activity, but its effectiveness is limited by poor tolerance when taken orally, making intranasal delivery a promising alternative for targeting brain tumors.

The study developed a highly sensitive method for measuring perillic acid (PA), a metabolite of POH, in rat plasma and brain, demonstrating that chitosan nanoemulsions significantly enhance the bioavailability of POH, suggesting improved therapeutic potential for brain cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal administration of perillyl alcohol-loaded nanoemulsion and pharmacokinetic study of its metabolite perillic acid in plasma and brain of rats using ultra-performance liquid chromatography/tandem mass spectrometry. da Silva Santos, J., Diedrich, C., Machado, CS., et al.[2021]

NEO100 significantly enhances the ability of trastuzumab to penetrate the blood-brain barrier (BBB), allowing for greater therapeutic activity against brain tumors in mouse models of HER2+ breast cancer.

When combined with NEO100, intravenous trastuzumab and the trastuzumab-drug conjugate T-DM1 resulted in improved overall survival for tumor-bearing mice, indicating a promising strategy for treating brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. Wang, W., He, H., Marín-Ramos, NI., et al.[2022]

Perillyl alcohol (POH) has shown potential as an anticancer agent, particularly with an intra-nasal formulation that produced promising results in patients with malignant glioma, despite less success with oral formulations.

POH's unique ability to cross biological barriers, such as the blood-brain barrier, enhances its value in drug development, allowing for innovative delivery methods and combinations with other therapeutic agents to create new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers. Chen, TC., da Fonseca, CO., Levin, D., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Perillyl alcohol for the treatment of temozolomide-resistant gliomas. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Detection of perillyl alcohol and its metabolite perillic acid in postsurgical glioblastoma tissue after intranasal administration of NEO100: illustrative case. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Microbial hydroxylation of S-(-)-perillyl alcohol by Fusarium heterosporium. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Intranasal administration of perillyl alcohol-loaded nanoemulsion and pharmacokinetic study of its metabolite perillic acid in plasma and brain of rats using ultra-performance liquid chromatography/tandem mass spectrometry. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Monoterpenoid Perillyl Alcohol: Anticancer Agent and Medium to Overcome Biological Barriers. [2021]