REC-2282 for Meningioma

(POPLAR-NF2 Trial)

No longer recruiting at 14 trial locations

Overseen By Recursion Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Recursion Pharmaceuticals Inc.

Must not be taking: Anti-tumor agents, Investigational drugs

Disqualifiers: Active malignancy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment, REC-2282 (also known as AR-42, NSC-D736012, or OSU-HDAC42), for individuals with progressive meningiomas (a type of brain tumor) that have a specific genetic mutation called NF2. Participants will receive either REC-2282 or a placebo, with different dosages tested. The trial is open to individuals aged 12 and older who have a measurable progressive meningioma and an NF2 mutation or related condition. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering hope for new treatment options.

Will I have to stop taking my current medications?

The trial requires that you have not taken an anti-tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), before screening. It does not specify about other medications, so you should discuss your current medications with the study team.

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

Research has shown that REC-2282, a treatment being tested for meningioma, was checked for safety in earlier studies. In these studies, REC-2282 was generally safe at doses up to 60 mg, though some patients experienced side effects. These side effects were not always serious but could be significant for some individuals.

The current trial for REC-2282 is a Phase 2/3 study. While earlier studies have demonstrated some safety, this trial aims to further confirm its safety and effectiveness in a larger group. Participants should understand that although some safety information exists, ongoing trials are essential for fully understanding the safety of REC-2282. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for meningioma?

Unlike the standard treatments for meningioma, which often involve surgery and radiation, REC-2282 offers a potential new approach by targeting specific pathways involved in tumor growth. Researchers are excited about REC-2282 because it could provide a non-invasive option that directly interferes with the molecular mechanisms driving the tumor, potentially reducing the need for more aggressive treatments. Additionally, the different dosage levels being tested, such as 40 mg and 60 mg, allow for tailoring the treatment to maximize effectiveness while minimizing side effects. This novel approach may offer hope for improved outcomes in both adults and adolescents with meningioma.

What evidence suggests that REC-2282 might be an effective treatment for meningioma?

Research has shown that REC-2282, also known as AR-42, may help treat NF2 mutated meningiomas, a type of brain tumor. Early studies suggest it works by affecting gene regulation, potentially slowing or stopping tumor growth. Initial research found REC-2282 to be generally well-tolerated, especially at doses like 60 mg, though some side effects raised concerns. In this trial, participants will receive either REC-2282 or a placebo, suggesting that REC-2282 could be a promising treatment option for individuals with these specific brain tumors. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older, weighing at least 40 kg, with progressive meningiomas linked to NF2 mutations. Participants must have adequate bone marrow function and provide consent. It's not for those likely needing surgery soon, who've had recent tumor treatments or other clinical trials drugs, are pregnant or planning pregnancy within 90 days post-trial.

Inclusion Criteria

I am 12 years or older and weigh at least 40 kg.

My bone marrow is working well.

I have a confirmed NF2 mutation or diagnosis.

Exclusion Criteria

Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP

Received another investigational drug within 30 days prior to screening

I haven't had any cancer except for cured localized ones in the past 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

Treatment

Participants receive REC-2282 or placebo, with dose determined from Cohort A for Cohort B

6 months

Safety Follow-up

Participants are monitored for safety after the end of treatment

4 weeks

Post-study Follow-up

Participants are monitored for progression-free survival and other outcomes

6 months

Open-label Extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• REC-2282

Trial Overview The study compares the effectiveness and safety of a new medication called REC-2282 against a placebo in patients with NF2 mutated meningiomas. The trial randomly assigns participants to either group and measures how well the tumors respond to treatment.

How Is the Trial Designed?

Group I: Cohort B REC-2282 Experimental Treatment 1 Intervention

Participants will receive REC-2282.

Group II: Cohort A Adults, REC-2282 60 mg Experimental Treatment 1 Intervention

Adult participants will receive REC-2282.

Group III: Cohort A Adults, REC-2282 40 mg Experimental Treatment 1 Intervention

Adult participants will receive REC-2282.

Group IV: Cohort A Adolescents, REC-2282 Experimental Treatment 1 Intervention

Adolescent participants will receive REC-2282.

Group V: Cohort B Placebo Placebo Group 1 Intervention

Participants will receive placebo.

Who Is Running the Clinical Trial?

Recursion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

450+

Published Research Related to This Trial

Stereotactic radiosurgery (SRS) significantly improves tumor control in patients with incidental meningiomas compared to observation, with a mean follow-up of over 3 years showing a very low tumor progression rate (pooled OR: 0.06).

Certain risk factors, including MRI T2 hyperintensity and larger initial tumor diameter, are associated with higher rates of tumor progression, suggesting that these factors can help predict which tumors may grow more rapidly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Versus Observation for Treating Incidental Meningiomas: A Systematic Review and Meta-Analysis. Zhang, C., Zhang, H.[2021]

In a study of 25 patients with nonresectable meningioma on long-term mifepristone therapy, fatigue was the most common side effect, affecting 22 patients, indicating a need for monitoring patient well-being during treatment.

While mifepristone can be safely administered for extended periods, regular ultrasound and thyroid function tests are recommended to monitor for potential complications like endometrial thickening and hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients receiving long-term treatment with mifepristone. Spitz, IM., Grunberg, SM., Chabbert-Buffet, N., et al.[2022]

Meningiomas are mostly benign tumors, and complete surgical resection is typically curative, making surgery the preferred treatment for symptomatic patients.

For patients with unresectable or recurrent meningiomas, stereotactic radiotherapy (SRT) is increasingly used as a less invasive alternative, especially for those at high surgical risk or with tumors in difficult locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meningiomas. Chamberlain, MC.[2020]

Recent literature highlights the exploration of new chemotherapeutic options for treating progressive and atypical meningiomas, indicating a growing interest in developing effective treatments for these challenging tumors.

Combination therapies targeting multiple molecular pathways show promise as potential adjuvant treatments, but further molecular studies are needed to better understand meningioma biology and identify specific therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Therapeutic Strategies in the Treatment of Meningioma. Caruso, G., Elbabaa, SK., Gonzalez-Lopez, P., et al.[2015]

In a review of 48 phase II clinical trials for meningioma, the most commonly used primary efficacy endpoint was progression-free survival (PFS), utilized in 38% of the trials, highlighting its importance in evaluating treatment effectiveness.

The study suggests that using multiple efficacy endpoints, particularly time-to-event measures, may be more appropriate for assessing outcomes in meningioma trials due to the complexity of the disease and variability in lesion characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy Endpoints in Phase II Clinical Trials for Meningioma: An Analysis of Recent Clinical Trials. Watanabe, S., Nonaka, T., Maeda, M., et al.[2023]

In a study of 43 meningioma tumors, histone deacetylase inhibitors (HDACi), particularly panobinostat, were found to significantly reduce cell viability in 36 tumors, indicating strong potential for epigenetic therapies in treating these tumors.

The research suggests that targeting epigenetic mechanisms, such as G9a and Jumonji-domain inhibition, could be effective for meningiomas, especially as sensitivity to these treatments increased with tumor grade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies. Tatman, PD., Wroblewski, TH., Fringuello, AR., et al.[2023]

The treatment for patients with subtotally resected or recurrent meningiomas, especially WHO grade II and III tumors, is not well established, highlighting a significant gap in high-quality evidence for effective interventions.

There is a pressing need for high-quality, multicenter clinical trials to explore optimal treatment strategies for these patients, as current therapies show minimal impact on survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opportunities for clinical research in meningioma. Vogelbaum, MA., Leland Rogers, C., Linskey, MA., et al.[2021]

In a study of 164 patients with recurrent grade 1 and 2 meningiomas, loss of H3K27me3 expression was found in 83 patients and was significantly associated with a higher risk of earlier re-recurrence, indicating its potential as a prognostic marker.

The study demonstrated that loss of H3K27me3 is an independent factor predicting shorter progression-free survival (PFS) in recurrent grade 1 meningiomas, suggesting that H3K27me3 testing could be beneficial in clinical settings for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of H3K27me3 expression enriches in recurrent grade 1&2 meningiomas and maintains as a biomarker stratifying progression risk. Hua, L., Ren, L., Wu, Q., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05130866

NCT05130866 | Efficacy and Safety of REC-2282 in ... Cohort A (Phase 2) will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8162746/

A Phase 1 trial of the histone deacetylase inhibitor AR-42 in ... This phase I trial was an open-label, single-center, dose-escalation study of single-agent AR-42 in primary central nervous system and advanced solid tumors.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/lio2.643

Early phase clinical studies of AR‐42, a histone ... AR-42 was generally well tolerated at 60 mg among the patients with NF2 or sporadic meningioma, though the incidence of toxicities may not be acceptable for ...

4. aacrjournals.org aacrjournals.org/cancerres/article/73/2/792/590752/Histone-Deacetylase-Inhibitor-AR-42-Differentially

Histone Deacetylase Inhibitor AR-42 Differentially Affects Cell ... Preclinical investigations establish the potential utility of a pan-HDAC inhibitor in treatment of meningioma, a type of brain tumor.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20535404

Efficacy and Safety of REC-2282 in Participants with ... The purpose of this study is to investigate the effectiveness and safety of REC-2282 in patients with progressive NF2 mutated meningiomas who ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05130866

NCT05130866 | Efficacy and Safety of REC-2282 in ... This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in participants with progressive NF2 mutated ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05130866?term=neurofibromatosis%202&viewType=Table&rank=5

Study Details | Efficacy and Safety of REC-2282 in Patients ... A method used to assign participants to an arm of a clinical study. The types of allocation are randomized allocation and nonrandomized. ... A group or subgroup ...