This clinical trial is testing a new, investigational treatment for people living with specific types of aggressive brain tumours – Grade 3 or 4 gliomas that have an IDH1 mutation. The goal is to learn more about how this treatment works, how it moves through the body, and whether it can help slow or stop tumour growth.
The trial is sponsored by NeOnc Technologies Holdings, Inc., a company dedicated to developing novel treatments for brain cancers.
NEO100 is a specially purified form of a natural compound called perillyl alcohol, which is found in essential oils from plants like peppermint and lavender. In laboratory studies, this compound has shown the potential to slow or stop the growth of certain cancer cells.
For this trial, NEO100 is given through the nose using a gentle mist (via a nebuliser and mask), four times a day. This delivery method helps the medicine reach the brain more directly and has been shown to be well tolerated in early studies.
Scientists believe that NEO100 may help by encouraging cancer cells to self-destruct (a process called apoptosis) and by helping open the blood-brain barrier, making it easier for medicines to reach the brain.
You may be eligible to take part if:
Participants in this study will receive NEO100 as part of the trial and will be closely monitored by medical professionals at approved clinical sites.
More detailed eligibility information is available on ClinicalTrials.gov.
You’ll also undergo regular scans and check-ins to monitor your progress.
A glioma diagnosis can be overwhelming. But science is moving forward — and so is hope. This trial represents a step towards understanding and possibly improving treatment for those affected by aggressive brain tumours with IDH1 mutations.
By taking part, you could help advance knowledge and potentially benefit from a treatment not yet widely available.
The NEO100-01 clinical trial is available at several leading medical centres across the United States. You can take part in the study at one of the following locations:
The study has two phases, Phase 1 and Phase 2a.
This multi-site, Phase 1/2a 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 radiographically-confirmed progression of Grade 3 and Grade 4 glioma or recurrent primary or secondary Grade 4 glioma. Phase 1 is a standard cohort dose escalation 3+3 design used to determine the maximum tolerated dose for Phase 2a. There were 24 patients enrolled in Phase 1. There will be 25 patients enrolled in Phase 2a. For both phases of the study, NEO100 will be self-administered four times daily for 28-day treatment cycles until disease progression, death, or patient withdrawal from the study for any reason, whichever occurs first.
The Phase 1 portion of study of intranasally administered NEO100 in patients with recurrent GBM after failure of standard chemoradiation with temozolomide was completed in June of 2019. Twelve patients were enrolled. Successive cohorts of 3 patients each received intranasal NEO100 at escalating dosages of 384 mg/d, 576 mg/d, 768 mg/d and 1152 mg/d. Patients self-administered these amounts, which were divided into 4 equal doses approximately 5-6 hours apart throughout each day. Phase 2a of the study is currently ongoing.
When determining safety, of the drug during phase 1, no severe (grade 3 or 4) adverse effects were noted in any of the cohorts during any of the monthly cycles. Other adverse effects (grade 1) consisted of nasal soreness or itching, runny nose, skin irritation around the nose, or headache. Repeated grade 2 leukopenia was noted in one patient of Cohort 2, but causality to NEO100 treatment was unclear.
It is believed the mechanism of action of NEO100 is similar in both patients with progressive or recurrent Grade IV gliomas who have IDH1 mutations and patients with progressive or recurrent Grade III astrocytomas who have IDH1 mutations making inclusion of both populations appropriate for this study.
Twelve patients were enrolled in Phase 1 portion of the trial.
A total of 28 patients with confirmed IDH1 mutation will be enrolled into the maximum tolerated dose Phase 2a study, based on the following assumptions for statistical power:
The Phase 1 study was a first-in-human study NEO100, designed primarily to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). It’s a critical starting point in clinical development and has established that the product is safe to be administered in humans.
The Phase 2a section of the study is an early phase study focused on providing initial evidence of efficacy, and further safety evaluation in a small group of patients. It bridges Phase 1 (safety and tolerability) and Phase 2b (larger efficacy trials).
Patients will remain on study treatment as long as the drug is works for them, until disease progression, death, or withdrawal for any reason (End of Study), whichever occurs first. After the last dose of study medication, patients will be followed for PFS-6, PFS, and OS with visits or phone calls every three months until death or the start of another anti-cancer therapy and until the study analysis is performed, which will be after all patients have reached the six month time point from their first dose.
The safety data from 15 clinical studies in more than 500 subjects indicate that daily treatments of perillyl alcohol administered orally or intranasally are generally mild and well tolerated.
The oral studies utilized daily doses of perillyl alcohol up to almost 30 g/day (14700 mg/m2/day). This high dose is more than 25-fold higher than the high dose proposed in the current IND (97 to 553 mg/m2/day, intranasally). The majority of the treatment-related AEs observed in the oral studies were grade 1/2 gastrointestinal, with a small number of grade 3 and 4 AEs (nausea, vomiting, hyperkalemia). The study reports indicate that some patients could not tolerate the long term regimen and discontinued participation in the study due to the AEs. The gastrointestinal AEs are likely to be related to the high dose levels used in these studies. Two of the 13 oral studies reported grade 3 or 4 thrombocytopenia, leukopenia, and neutropenia, observed at doses of 3500 and 4800 mg/m2/day. These AEs were not considered to be related to study treatment.
The intranasal studies utilized daily doses of perillyl alcohol ranging from 80 to 2240 mg/m2/day. The treatment-related AEs observed in the intranasal studies were generally grade 1 or 2 and included nose redness, respiratory (cough) – likely related to transient nasal irritation the site of administration. The intranasal studies also reported AEs that were shared with the oral studies, including gastrointestinal (nausea, vomiting, diarrhea, constipation), leukopenia (grade 2), and CNS confusion / lack of awareness.
Use of NEO100 in 12 patients participating in the Phase I portion of the NEO100-01 Phase I portion of the study appear to confirm these findings.
In August 2024, in an intranasal NEO100 Phase 2a meningioma study in the United States (NEO100-02) one patient was hospitalized for febrile neutropenia. The event was officially reported as febrile Neutropenia Grade 3, lymphocytopenia Grade 3, neutropenia Grade 3 and thrombocytopenia Grade 1. NEO100 was held until the patient’s counts recovered and then the patient was restarted on NEO100. The event was deemed to be potentially related to NEO100 and was similar in severity and duration to neutropenia seen previously in patients receiving oral perillyl alcohol in clinical trials. The subsequent and final report was updated to confirm the event and patient lab data met criteria for only neutropenia and thrombocytopenia; not febrile neutropenia and/or lymphocytopenia as initially reportedNo deaths are known to be attributed to perillyl alcohol treatment.
No deaths are known to be attributed to perillyl alcohol treatment.
Throughout the course of the study, all efforts will be made to remain alert to possible AEs. The term “AEs” includes both Serious Adverse Events (SAEs) and Non-Serious AEs. If an AE occurs, the first concern will be the safety of the patient and appropriate medical intervention if necessary.
AEs will be monitored and reported on the AE eCRF, including AE description, onset date, stop date, frequency, severity, seriousness, relationship to study product, action taken regarding study product, concomitant treatment, and outcome.
Yes, MRI with gadolinium will be performed at the Pre-Study visit, end of Cycles 2, 4, 6. 8, etc (End of Study, Day 28 + 7 days) as per standard of care and read by the MRI central reader. If more than 14 days elapse after the pre-Study MRI, an additional MRI will be required prior to initiation of treatment.
All AEs that occur after the first dose of study product and through 30 days after the last dose of study drug will be recorded. Each patient will be assessed for the development of toxicity. Toxicity will be assessed according to the NCI CTCAE, version 5.0. Dose adjustments will be made according to the system showing the greatest degree of toxicity.
Clinical judgment will be used to determine appropriate management of the patient during any AE. Dose interruptions may occur as a result. A dose interruption occurs when either NEO100 inhalation is interrupted (i.e., intra- inhalation interruption), or no inhalation occurs under the next scheduled dose (missed dose). Interruptions resulting in the permanent discontinuation of the study drug will be documented accordingly.
Following a dose interruption, patients will be restarted at the next lower dose.
If you require medical care/treatment as a result of injury arising from your participation in this research study, emergency medical care/treatment will be provided. The sponsor will pay for the cost of care/treatment for those injuries related to your participation in the research study that are not covered by your private insurance company or third party payor (excluding any government health benefit programs, in which case the sponsor will pay for all of the reasonable medical bills). No other form of compensation will be provided for injuries resulting from your personal conduct or participation in activities outside of the scope of the study protocol. No financial compensation will be routinely provided for such things as lost wages, disability or discomfort, losses claimed by spouses or family members, medical expenses due to treatment of any underlying or unrelated condition, or any expense arising from or claimed to be due to any research-related injury.
There is no guarantee that NEO100 can relieve a patients symptoms or stop progression of their cancer, and your symptoms could remain unchanged. Therefore, there may be no direct benefit to you from participating in this study. However, the information collected from this study may help researchers develop new tests or drugs that may help others with GBM in the future.
The Phase I portion of the study of NEO100 was conducted in 12 patients with recurrent GBM. NEO100 was administered by intranasal delivery using a nebulizer and nasal mask. Intranasal glioma therapy with NEO100 was well tolerated at all dose levels and no adverse events were reported. PFS-6 was 33%, OS-12 was 55%, and median OS was 15 months.
Four patients (33%) survived >24 months. This prompted the study team to perform secondary analysis of the data based upon Isocitrate Dehydrogenase Type 1 (IDH1) status in patients. IDH enzymes catalyze the oxidative carboxylation of isocitrate and play key roles in the Krebs cycle and cellular homeostasis. Treatment with NEO100 in IDH1 mutant recurrent GBM resulted in an unexpected length of progression free survival with an average of 32 months and increased survival in three IDH1 cases (average 32 months).
If a patient demonstrates disease progression (excluding pseudo progression) they may be discontinued from the study. The standard of care (SOC) definition for pseudo progression will be followed and is defined by increased contrast enhancement, no change in perfusion measurement.
If you are discontinued from the study as a result of disease progression, your doctor will discuss further treatment options with you, that may include standard of care therapy or another clinical trial.
All research tests and procedures provided to you for this research study are being paid for by the sponsor. Neither you nor your health plan/insurance company will be charged for the cost of any research tests or procedures that are being done for this research study. Should you require any routine tests or procedures to treat your illness that are not related to this research study that you would normally have if you were not participating in this research study, you and/or your health plan/insurance company will be billed for the cost of those routine tests or procedures and you will be responsible for your standard co-payments and deductibles.
The mask and study drug supplies will be provided by the study sponsor free of charge while you are participating in this research study.
You will not get paid for being in this study. However, you will get $75 for travel and parking costs for each visit to the clinic you complete. This payment will help defray the cost for travel and parking costs for each scheduled visit. The study doctor or study staff can tell you more about this reimbursement and when you will receive it.
Supportive care will be provided prior to and during this trial, as clinically indicated, and in accordance with the standard practices of the field. This includes the use of corticosteroids, anti-convulsants, and pain medications.
Any medication considered necessary for the patient’s welfare, and which is not expected to interfere with the evaluation of the study drug, may be given at the discretion of the investigator.
In total, you will be in the clinic about 4 hours for this first day of treatment. Before you leave the clinic, a diary will be given to you to record the time and other information about your daily nasal delivery. Also, you will be given the study drug treatment supplies, an instruction manual, and an instruction sheet so that you can take the study drug at home. The study treatment supplies include drug administration packages, a nasal mask, and a nebulizer (air) pump.
After this visit, starting at Day 2, you will take the study drug 4 times a day. You will continue study treatment at home where you can keep your regular daily routine. Each study treatment course will include daily NEO100 study supplies sufficient for 28-days. You should plan on returning to the clinic to obtain an additional supply of the drug on day 28 or day 29. You may continue to take study drug after Day 28 for up to an additional 7 days, between the end of a cycle and when you return to the clinic.
During the study, you will need to return to the hospital outpatient clinics where you will be examined by a doctor physically, and undergo routine laboratory tests and procedures similar to Day 1. Additionally, a routine MRI of the head will be performed to assess your tumor. MRI with gadolinium will be performed at the Pre-Study visit, at the end of even Cycles 2, 4,6 and so forth per standard of care. These routine visits will continue for as long as you remain on treatment.
Your participation in this study is voluntary. Your decision not to take part will not affect your current or future care at this institution. If you decide to take part in this study, you are free to change your mind and stop being in the study at any time. Both decisions will not cause any penalty or loss of benefits to which you are otherwise entitled. You are not waiving any legal claims or rights.
You may withdraw consent to participate in the study at any time.
Patients will be treated on study until progression of disease, death or withdraw for any reason.
The result of the study will be reported in a Clinical Study Report generated by NeOnc, and will contain all data from all investigational sites.
This is an investigational treatment and part of an ongoing clinical trial. Participation is voluntary and requires consent. All personal information is kept confidential and used only for study purposes.
