REC-2282 for Meningioma
(POPLAR-NF2 Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Recursion Pharmaceuticals Inc.
Must not be taking: Anti-tumor agents, Investigational drugs
Disqualifiers: Active malignancy, Pregnancy, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called REC-2282 to see if it can help treat specific brain tumors in patients who haven't responded to other treatments. The study will check if the drug can slow down or stop the growth of these tumors.
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.
What data supports the effectiveness of the drug REC-2282 for treating meningioma?
Research suggests that targeting epigenetic mechanisms, like using histone deacetylase inhibitors (HDACi), can be effective in treating meningiomas. In a study, HDAC inhibitors significantly reduced cell viability in most meningioma tumors tested, indicating potential effectiveness for drugs like REC-2282, which may have similar mechanisms.
12345What makes the drug REC-2282 unique for treating meningioma?
REC-2282, also known as AR-42, is a novel treatment option for meningioma that may offer a new approach compared to traditional methods like surgery and radiotherapy. It is part of ongoing research to find effective medical treatments for meningiomas, especially for cases where surgery and radiotherapy are not viable or have failed.
14678Eligibility Criteria
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.
+2 more
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.
+3 more
Trial Timeline
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
Participant Groups
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.
5Treatment groups
Experimental Treatment
Placebo Group
Group I: Cohort B ActiveExperimental Treatment1 Intervention
Dose TBD
Group II: Cohort A Adults, Dose 60 mgExperimental Treatment1 Intervention
Group III: Cohort A Adults, Dose 40 mgExperimental Treatment1 Intervention
Group IV: Cohort A AdolescentsExperimental Treatment1 Intervention
Starting dose of 30 mg followed by dose escalation to 40 mg and 60 mg.
Group V: Cohort B PlaceboPlacebo Group1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sarah Cannon Cancer Institute - HCA MidwestOverland Park, KS
House InstituteLos Angeles, CA
University of California Los AngelesLos Angeles, CA
Massachusetts General HospitalBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Recursion Pharmaceuticals Inc.Lead Sponsor
References
Management of patients receiving long-term treatment with mifepristone. [2022]To determine clinical side effects and biochemical and hematological abnormalities in patients with nonresectable meningioma on long-term mifepristone (RU 486) therapy.
High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies. [2023]Background  Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas. Methods  We screened a 43-tumor cohort using a 139-compound epigenetic inhibitor library to assess sensitivity of relevant meningioma subgroups to epigenetic inhibition. The cohort was composed of 5 cell lines and 38 tumors cultured directly from surgery; mean patient age was 56.6 years ± 13.9 standard deviation. Tumor categories: 38 primary tumors, 5 recurrent; 33 from females, 10 from males; 32 = grade 1; 10 = grade 2; 1 = grade 3. Results  Consistent with our previous results, histone deacetylase inhibitors (HDACi) were the most efficacious class. Panobinostat significantly reduced cell viability in 36 of 43 tumors; 41 tumors had significant sensitivity to some HDACi. G9a inhibition and Jumonji-domain inhibition also significantly reduced cell viability across the cohort; tumors that lost sensitivity to panobinostat maintained sensitivity to either G9a or Jumonji-domain inhibition. Sensitivity to G9a and HDAC inhibition increased with tumor grade; tumor responses did not separate by gender. Few differences were found between recurrent and primary tumors, or between those with prior radiation versus those without. Conclusions  Few efforts have investigated the efficacy of targeting epigenetic mechanisms to treat meningiomas, making the clinical utility of epigenetic inhibition largely unknown. Our results suggest that epigenetic inhibition is a targetable area for meningioma pharmacotherapy.
Opportunities for clinical research in meningioma. [2021]Meningiomas, when benign, are commonly treated with surgical resection alone. However, the optimal treatment for patients with subtotally resected or recurrent World Health Organization (WHO) grade I tumors, or WHO grade II and III tumors, regardless of the extent of resection, is not well defined, with both a paucity of high quality published evidence as well as a perceived minimal clinical effect for currently available interventions, specifically in terms of prolonging survival. In consideration of the size of the patient population with incompletely treated or non-benign meningiomas, there are opportunities for conducting high quality, prospective, multicenter clinical trials. In this review, we discuss a number of trials that were attempted and/or completed by cooperative groups or clinical consortia, and describe areas of clearly unmet need in terms of defining the optimal treatment regimens. Finally, we discuss ongoing efforts to develop new trials to more definitively address important therapeutic questions.
Innovative Therapeutic Strategies in the Treatment of Meningioma. [2015]Few medical options are available for progressive/recurrent and atypical/anaplastic meningiomas. New developments in chemotherapeutic options for meningiomas have been explored over the past decade. We review the more recent literature to recognize studies investigating recent medical and chemotherapeutic agents that have been experienced or are currently being tested for meningiomas. Combination therapies affecting multiple molecular targets are currently opening up and present significant promise as adjuvant therapeutic options. However, there is an evident need for new molecular studies in order to better understand the biology of meningiomas and, thus, to identify new and more specific therapeutic targets.
Loss of H3K27me3 expression enriches in recurrent grade 1&2 meningiomas and maintains as a biomarker stratifying progression risk. [2023]To determine if loss of H3K27me3 could predict higher risk of re-recurrence in recurrent meningiomas.
Stereotactic Radiosurgery Versus Observation for Treating Incidental Meningiomas: A Systematic Review and Meta-Analysis. [2021]To evaluate the clinical outcomes of incidental meningiomas (IM) treated with stereotactic radiosurgery (SRS) or observation.
Efficacy Endpoints in Phase II Clinical Trials for Meningioma: An Analysis of Recent Clinical Trials. [2023]Response Evaluation Criteria in Solid Tumors (RECIST)-based response rates are commonly used as efficacy endpoints in phase II clinical trials for solid tumors. However, no consensus has been reached concerning adequate efficacy endpoints for phase II clinical trials targeting meningioma. Irregularity of lesions after resection, and varying degrees of dysplasia and histologic subtypes make establishing an appropriate efficacy evaluation difficult.
Meningiomas. [2020]Meningiomas are extra-axial brain tumors of middle-to-late adult life and show a predominance in women. Overall, 90% of meningiomas are benign, 6% atypical, and 2% are malignant. Most patients diagnosed with a meningioma decide to have it removed surgically, and are advised to do so based on their neurologic symptoms. Complete surgical resection is usually curative. For incompletely resected or recurrent tumors not previously irradiated, radiotherapy is administered. Radiotherapy may be administered as either conventional external beam irradiation or stereotactically. Stereotactic radiotherapy (SRT) either as LINAC or gamma knife radiosurgery is increasingly utilized. Advocates of SRT have suggested this therapy as an alternative to surgery particularly in poor surgical risk patients, patients with meningiomas in eloquent or surgically inaccessible locations, and in those patients of advanced age. When the meningioma is unresectable or all other treatments (surgery, radiotherapy) have failed, immunochemotherapy may be considered. Hydroxyurea, alpha interferon, tamoxifen, and mifepristone (RU-486) have been modestly successful in pateints with recurrent meningiomas whereas cyclophosphamide, Adriamycin (Pharmacia and Upjohn, Bridgewater, NJ) and vincristine (CAV), ifosfamide/Mesna (Bristol-Meyers Squibb, Princeton, NJ) or Adriamycin/dacarbazine (DTIC) have been administered to patients with aggressive or malignant meningiomas.