Perillyl Alcohol for Glioblastoma

Recruiting at 9 trial locations

Overseen By Chloe Richmond

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neonc Technologies, Inc.

Must not be taking: Bevacizumab, Gliadel, others

Disqualifiers: Large tumor, Multifocal tumor, others

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

Compensation: Varies

Number of Visits: Unknown

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called perillyl alcohol for individuals with aggressive brain tumors, specifically Grade IV gliomas or recurrent Grade III astrocytomas. Researchers seek to determine the safety and effectiveness of this treatment and identify the optimal dose. The treatment involves using a nasal spray four times a day. Eligible participants have brain tumors that have returned or progressed despite previous treatments like radiation. Those with an IDH1 mutation (a specific genetic change in the tumor) may be well-suited for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be on a stable dose of steroids for at least five days before joining, and if you have seizures, your anti-epileptic medication must be stable for 14 days prior to consent.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that perillyl alcohol, administered as NEO100 through the nose, is generally well-tolerated by patients with gliomas, a type of brain tumor. In previous studies, patients reported few side effects from this treatment. One study found that this method improved survival rates compared to past data on similar patients.

In clinical tests, over 500 people have received NEO100, and the safety results appear promising. Most patients did not experience serious problems, suggesting it may be a safe option for those considering joining the trial. However, as with any treatment, individual experiences may vary, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for glioblastoma, which often involve chemotherapy and radiation, perillyl alcohol is delivered intranasally, allowing it to bypass the blood-brain barrier more effectively. This unique delivery method is particularly exciting because it may enhance the drug's ability to reach the brain tumor directly. Additionally, perillyl alcohol is derived from natural sources and works differently by potentially disrupting cancer cell membranes, offering a novel approach to tackling this aggressive brain cancer. Researchers are hopeful that these features could lead to improved outcomes for patients with glioblastoma.

What evidence suggests that perillyl alcohol might be an effective treatment for glioblastoma?

Research has shown that perillyl alcohol, also known as NEO100, may help treat glioblastoma, a type of brain cancer. Studies have found that patients with recurring glioblastoma who received perillyl alcohol lived longer than those who did not. Specifically, one study revealed that about 58% of these patients were still alive after 12 months, surpassing past results. In this trial, participants will receive NEO100 through intranasal delivery. Some in the Phase 1 arm will receive escalating doses to determine the maximum tolerated dose, while others in the Phase 2A arm will receive the maximum tolerated dose. Perillyl alcohol blocks certain proteins that are often overly active in glioblastoma tumors, potentially slowing the cancer's growth. Additionally, patients have tolerated perillyl alcohol well, with no serious side effects reported in trials. ^{1 2 6 7 8}

Who Is on the Research Team?

Josh Neman, PhD

Principal Investigator

NeOnc Technologies Holdings, Inc.

Thomas Chen, MD, PhD

Principal Investigator

NeOnc Technologies Holdings, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with Grade IV glioma that has progressed after radiation or temozolomide treatment. They must have a life expectancy of at least three months, be in fair to good physical condition (ECOG 0-2 or KPS ≥60), and not have had recent surgery or chemotherapy. Participants need stable steroid use before consent, adequate organ function, and agree to contraception.

Inclusion Criteria

Must have the ability to understand, and the willingness to sign, a written informed consent.

Must have an expected survival of at least three months.

I agree to use birth control during the study.

Exclusion Criteria

I finished chemo-radiation within the last 3 months, unless my cancer has grown or spread.

I had surgery within the last week.

Patient is receiving any other investigational agents.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Intranasal delivery of NEO100 (perillyl alcohol) four times a day, escalation up to four different doses to determine maximum tolerated dose

28-day treatment cycles

Phase 2A Treatment

Intranasal delivery of NEO100 (perillyl alcohol) four times a day at maximum tolerated dose

28-day treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Perillyl alcohol

Trial Overview NEO100 (perillyl alcohol) is being tested through nasal administration for its safety and effectiveness against recurrent Grade IV glioma. The study includes two phases: Phase 1 determines the maximum tolerated dose via a '3+3' design; Phase 2a treats patients with this dose. Up to six cycles of NEO100 are given daily over a period of four weeks each.

How Is the Trial Designed?

Group I: NEO100 Phase 2A Experimental Treatment 1 Intervention

Intranasal delivery of NEO100 (perillyl alcohol) four times a day. Treatment of total of 25 patients at maximum tolerated dose.

Group II: NEO100 Phase 1 Experimental Treatment 1 Intervention

Intranasal delivery of NEO100 (perillyl alcohol) four times a day, escalation up to four different doses to determine maximum tolerated dose.

Who Is Running the Clinical Trial?

Neonc Technologies, Inc.

Lead Sponsor

Trials

4

Recruited

230+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7879254/

Phase I trial of intranasal NEO100, highly purified perillyl ... Intranasal glioma therapy with NEO100 was well tolerated. It correlated with improved survival when compared to historical controls.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02704858

NCT02704858 | Safety and Efficacy Study in Recurrent or ... A study revealed that H-Ras and K-Ras farnesylation were inhibited by perillyl alcohol. Ras activity is elevated in malignant glioma tumors. Activated Ras ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11828245/

Efficacy of monoterpene perillyl alcohol upon survival rate ... Patients with recurrent primary GBM treated with POH survived significantly longer (log rank test, P < 0.0001) than untreated group. Patients with recurrent ...

4. neonc.com neonc.com/neo100-human-trial-in-adult-patients-with-recurrent-glioblastoma/

NEO100 Human Trial In Adult Patients With Recurrent ... Results of the study showed that Intranasal NEO100 was well tolerated at all dose levels and no severe adverse events were reported. PFS-6 was 33%, OS-12 was 58 ...

5. thejns.org thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/4/8/article-CASE22215.xml

Detection of perillyl alcohol and its metabolite perillic acid in ... Preclinical data have demonstrated chemopreventive and cancer therapeutic activity of POH in a number of preclinical tumor models, including GBM ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06357377

A Study of the Safety, Dosing, and Delivery of NEO100 ... This is an open label, Phase 1b safety, dose-finding, brain tumor delivery, and pharmacokinetics study of intranasal NEO100 in patients with pediatric-type ...

7. anovaevidence.com anovaevidence.com/neonc-technologies-a-new-clinical-trial/

NeOnc Technologies - A New Clinical Trial - Anova NEO100 is a specially purified form of a natural compound called perillyl ... The safety data from 15 clinical studies in more than 500 subjects indicate ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6321279/

Intranasal Perillyl Alcohol for Glioma Therapy - PubMed Central Intriguingly, when switched to intranasal delivery, POH yielded highly promising activity in recurrent glioma patients and was well tolerated.