NEO212 for Brain Tumors

Recruiting at 1 trial location

Overseen By Chloe Richmond

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neonc Technologies, Inc.

Must be taking: Anti-epileptics

Must not be taking: QT prolonging drugs

Disqualifiers: Spinal cord metastases, Meningeal metastases, Secondary cancer, others

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

Compensation: Varies

Number of Visits: Unknown

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NEO212 for brain tumors. The goal is to assess its safety and effectiveness when used alone for certain brain tumors, such as Astrocytoma and Glioblastoma, or in combination with other standard treatments for cancers that have spread to the brain. Suitable candidates for this trial include individuals with brain tumors or cancers that have metastasized to the brain and are not controlled by surgery or radiation. As a Phase 1/Phase 2 trial, the research aims to understand how NEO212 works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to potentially benefit from this new treatment.

Will I have to stop taking my current medications?

Participants may need to stop certain medications before starting the trial. There is a required 'washout period' (time without taking certain medications) for some treatments, such as 28 days for experimental agents and 7 days for non-cytotoxic agents. However, if you are on a protocol-approved Standard of Care regimen, you may continue it during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NEO212 could be a promising treatment for brain tumors and appears to be safe. In earlier studies, patients with brain tumors such as malignant glioma tolerated NEO212, which contains Temozolomide, well. This indicates it did not harm normal tissues, including the bone marrow, where blood cells are made.

The current trial is in its early stages, and researchers are still gathering information on the safety of NEO212 for people. Early trials usually focus on safety, so reaching this stage generally indicates some safety observed in earlier tests. However, more data is needed to confirm these initial results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NEO212 for brain tumors because it offers a fresh approach compared to current treatments. NEO212 is derived from perillyl alcohol, which may enhance drug delivery across the blood-brain barrier, a notorious challenge in treating brain metastases. This treatment also allows for oral administration, which is more convenient than traditional intravenous methods. Additionally, when combined with standard treatments, it could potentially enhance efficacy against difficult-to-treat brain metastases and specific types of brain cancers like Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype.

What evidence suggests that this trial's treatments could be effective for brain tumors?

Research shows that NEO212, which participants in this trial may receive, may help treat brain tumors. Studies have found that NEO212 can slow the growth and spread of glioma stem cells, a type of brain tumor cell. In tests, NEO212 proved 2-3 times more effective than temozolomide, a common brain cancer drug, especially in cells responsive to temozolomide. Recent studies also showed that patients using NEO212 with radiation had better survival rates than those using radiation alone. These findings suggest that NEO212 could effectively manage brain tumors and improve survival. ^{1 3 6 7 8}

Who Is on the Research Team?

Vincent Simmons, PhD

Principal Investigator

NeOnc Technologies

Patrick Walters

Principal Investigator

NeOnc Technologies

Tom Chen, MD, PhD

Principal Investigator

NeOnc Technologies

Are You a Good Fit for This Trial?

This trial is for adults with specific brain cancers (Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype) or uncontrolled brain metastasis from solid tumors. Participants must have completed prior treatments and be on stable steroids. They should understand the study and consent to join. Those recently treated with certain drugs or therapies may need to wait before joining.

Inclusion Criteria

The patient must possess the cognizance to comprehend, as well as the eagerness to sign a legally binding informed consent document.

I am in the first phase of the trial, focusing on finding the right dose.

It's been over a week since I last took non-chemotherapy cancer drugs or herbal medicine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1

Dose escalation study to determine the maximum tolerated dose (MTD) of NEO212

6 months

Regular visits for dose escalation and monitoring

Phase 2a

Safety run-in study to confirm the safety of the MTD/RP2D of NEO212 with select SOC regimens

6 months

Regular visits for safety assessment and monitoring

Phase 2b

Dose expansion study to assess efficacy of NEO212 alone and in combination with SOC regimens

6 months

Regular visits for efficacy assessment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• FOLFIRI Protocol
• Ipilimumab
• NEO212
• Nivolumab
• Paclitaxel
• Pembrolizumab
• Regorafenib

Trial Overview NEO212 Oral Capsule is being tested in patients with certain types of brain cancer and those with uncontrolled brain metastasis alongside standard-of-care treatments. The trial will assess safety, how the body processes the drug, and its effectiveness across three phases: dose escalation (Phase 1), initial efficacy testing (Phase 2a), and expanded efficacy evaluation (Phase 2b).

How Is the Trial Designed?

Group I: Phase 2b efficacy - NEO212 for Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype Experimental Treatment 1 Intervention

Patients receiving NEO212 alone for treatment of Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules.

Group II: Phase 2b efficacy - NEO212 & SOC for Uncontrolled Metastases to the Brain Experimental Treatment 9 Interventions

Patients receiving NEO212 in combination with select standard of care treatments for treatment of uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. SOC treatments established to be safe in Phase 2a of the study will be used in this arm of Phase 2b.

Group III: Phase 2a Safety Run-In - NEO212 and Stivarga (Regorafenib) Experimental Treatment 2 Interventions

\- Colorectal cancer (CRC) with uncontrolled metastases to the brain who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anU-EGFR therapy. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Stivarga - 160 mg orally, once daily for the first 21 days of each 28-day cycle per package insert

Group IV: Phase 2a Safety Run-In - NEO212 and Pembrolizumab Experimental Treatment 2 Interventions

The following primary cancers with uncontrolled metrastases to the brain: * Unresectable or metastatic melanoma. * NSCLC expressing PD-L1, with no EGFR or ALK genomic tumor aberrations. * Metastatic NSCLC whose tumors express PD-L1. * EGFR or ALK genomic tumor aberrations must have disease progression. * SCLC. * Unresectable, recurrent HNSCC whose tumors express PD-L1. * HNSCC on or after platinum-containing chemotherapy. * Urothelial carcinoma whose tumors express PD-L1. * Urothelial carcinoma. * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). * Microsatellite Instability-high or Mismatch Repair Deficient Colorectal Cancer (CRC). * Gastric or gastroesophageal junction adenocarcinoma. * Esophageal or gastroesophageal juncUon (GEJ). * Cervical cancer. * Merkel cell carcinoma. NEO212 - Same as Arm 1. Pembrolizumab - 200 mg administered every 3 weeks per package insert.

Group V: Phase 2a Safety Run-In - NEO212 and Nivolumab Experimental Treatment 2 Interventions

The following primary cancers with uncontrolled metrastases to the brain: * Unresectable or metastatic melanoma. * Metastatic non-small cell lung cancer. * Advanced renal cell carcinoma. * Squamous cell carcinoma of the head and neck. * Urothelial carcinoma. * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. * Unresectable esophageal squamous cell carcinoma (ESCC). NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Nivolumab - 240 mg administered every 2 weeks per package insert

Group VI: Phase 2a Safety Run-In - NEO212 and Ipilimumab Experimental Treatment 2 Interventions

\- Unresectable or metastatic melanoma with uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Ipilimumab - 3 mg/kg administered IV over 90 minutes every 3 weeks for a maximum of 3 doses per package insert.

Group VII: Phase 2a Safety Run-In - NEO212 and FOLFIRI (Zaltrap) + Bevacizumab (Avastin) Experimental Treatment 3 Interventions

\- Metastatic colorectal cancer (mCRC) with uncontrolled metastases to the brain, that is resistant to or has progressed following an oxaliplatin-containing regimen NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. FOLFIRI - 4 mg/kg aIV over 1 hour every 2 weeks. Bevacizumab - 10 mg/kg IV every 2 weeks.

Group VIII: Phase 2a Safety Run-In - NEO212 and CarbolaUn (ParaplaUn) + Paclitaxel (Taxol) Experimental Treatment 3 Interventions

\- Colorectal cancer (CRC) with uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles per package insert. Paclitaxel - 135mg/m2 IV administered over 24 hours, every 3 weeks per package insert.

Who Is Running the Clinical Trial?

Neonc Technologies, Inc.

Lead Sponsor

Trials

4

Recruited

230+

Published Research Related to This Trial

NEO212, a new anticancer drug, shows a higher concentration in brain tumor tissue compared to normal brain tissue, which suggests it could be an effective treatment for brain cancers.

The drug has a longer half-life in mouse plasma (94 minutes) and a better brain-to-plasma ratio than temozolomide (TMZ), indicating its potential for targeted therapy in brain-localized malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice. Cho, HY., Swenson, S., Thein, TZ., et al.[2022]

NEO212, a novel temozolomide analog, shows promising anticancer effects in ovarian cancer cells by inhibiting cell proliferation, causing DNA damage, and inducing apoptosis, as demonstrated through various assays including xenograft models and flow cytometry.

The mechanism of action involves the inhibition of the transcription factor EB (TFEB) translocation, which disrupts lysosomal function and autophagic flux, potentially overcoming autophagy-mediated chemotherapy resistance, making NEO212 a strong candidate for ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEO212 induces mitochondrial apoptosis and impairs autophagy flux in ovarian cancer. Song, X., Liu, L., Chang, M., et al.[2020]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, showing meaningful efficacy in delaying disease progression and maintaining quality of life in a study of 525 patients.

TMZ has a favorable safety profile and does not require liver metabolism for activation, allowing it to rapidly penetrate the cerebrospinal fluid, making it a promising option for treating these aggressive brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in malignant gliomas. Yung, WK.[2018]

OncoGel™, which delivers paclitaxel locally, significantly improved median survival in rats with gliosarcoma, extending it to 33 days compared to 15 days for untreated controls, and 50% of treated animals lived beyond 120 days.

Combining OncoGel with either oral or locally delivered temozolomide (TMZ) and/or radiotherapy resulted in over 50% of the animals achieving long-term survival, with some groups reaching 100% long-term survival, indicating a strong potential for enhanced treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of paclitaxel thermal gel depot with temozolomide and radiotherapy significantly prolongs survival in an experimental rodent glioma model. Vellimana, AK., Recinos, VR., Hwang, L., et al.[2021]

NEO212, a novel drug combining temozolomide with perillyl alcohol, shows greater cytotoxicity against temozolomide-resistant glioma cells compared to temozolomide itself, while sparing normal cells from toxicity.

In animal studies, NEO212 effectively reduces tumor growth and improves survival rates in mice with temozolomide-resistant gliomas, indicating its potential as a safe and effective treatment option for patients with this aggressive brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEO212, temozolomide conjugated to perillyl alcohol, is a novel drug for effective treatment of a broad range of temozolomide-resistant gliomas. Cho, HY., Wang, W., Jhaveri, N., et al.[2020]

In a phase II trial involving 32 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a 25% objective response rate, indicating its potential as an effective second-line treatment after PCV chemotherapy.

TMZ was generally well tolerated, with hematological side effects being the most common, and a median time to progression of 8 months for those who responded, suggesting it could be a viable option for patients who do not respond to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. van den Bent, MJ., Chinot, O., Boogerd, W., et al.[2020]

In a pilot study involving 11 patients with recurrent or treatment-induced malignant brain tumors, the combination of TMZ and oral VP-16 showed promising activity, with 45% of patients achieving a partial response to treatment.

The treatment was well-tolerated, with no major acute toxicity reported during 52 treatment courses, and 45% of patients remained progression-free at 6 months, indicating the need for further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of the rate of response, safety, and tolerability of temozolomide and oral VP-16 in patients with recurrent or treatment-induced malignant central nervous system tumors. Terasaki, M., Bouffet, E., Katsuki, H., et al.[2018]

Citations

1. neonc.com neonc.com/neo212/

NEO212 - NeOnc Technologies Holdings, Inc ... Recent studies demonstrate its impact, showing 1-year and 2-year survival rates of 37.8% and 10.4% respectively, with radiation plus TMZ, compared to 22.2% and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06047379

Safety and Efficacy of NEO212 in Patients with Astrocytoma ... This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5935548/

NEO212 Inhibits Migration and Invasion of Glioma Stem Cells These studies indicate that NEO212, in addition to cytotoxicity, can effectively reduce migration and invasion in GSCs, thus exhibiting significant clinical ...

4. aacrjournals.org aacrjournals.org/mct/article/13/8/2004/91845/NEO212-Temozolomide-Conjugated-to-Perillyl-Alcohol

NEO212, Temozolomide Conjugated to Perillyl Alcohol, Is a ... The results show that NEO212 is 2- to 3-fold more effective than temozolomide on temozolomide-sensitive cells; the IC50 results are summarized in Table 1.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/434515

Safety and Efficacy of NEO212 in Patients with Astrocytoma ... This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose ...

6. withpower.com withpower.com/trial/phase-2-carcinoma-merkel-cell-9-2023-fedc3

NEO212 for Brain Tumors Temozolomide, a component of NEO212, has shown an acceptable safety profile in clinical studies for treating malignant glioma, a type of brain tumor. This ...

7. neonc.com neonc.com/portfolio/neo212-tumor-trial/

NEO212 Tumor Trial The NEO212 Tumor Trial is an open-label phase 1/2 dose-finding, safety and efficacy study of orally administered NEO212 in patients with astrocytoma IDH-mutant, ...

8. ctv.veeva.com ctv.veeva.com/study/safety-and-efficacy-of-neo212-in-patients-with-astrocytoma-idh-mutant-glioblastoma-idh-wildtype-or

Safety and Efficacy of NEO212 in Patients with Astrocytoma ... This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose ...