Abemaciclib in Newly Diagnosed Meningioma Patients

Study Overview
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Brief Summary
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This study is being done to learn about how an investigational drug called abemaciclib works in treating patients with a newly-diagnosed grade 3 meningioma. Abemaciclib is a drug that is approved by the FDA, but not for brain tumors. Participants who consent to the trial will have surgical tissue collected from the planned surgical resection and tested. If the tissue shows positive results for RB cells and participants are qualified, they will be enrolled and receive study treatment two to five weeks after completing standard-of-care radiation therapy. This is a randomized clinical trial which means that participants will be randomly assigned to a treatment based on chance, like a flip of a coin. Neither the participant nor the researcher chooses the assigned group. Randomization will help the researchers study how the drug works by comparing the difference between the study drug and the placebo and how they work in treating brain tumors. This is a double-blinded study, which means that neither the participant nor the study team will know which treatment the participant is receiving.

Official Title
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A Phase 2 Multicenter, Double-blind, Randomized-controlled Study of Abemaciclib (CDK4 and 6 Inhibitor) in Newly Diagnosed RB-proficient Grade 3 Meningioma Participants

Conditions
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Meningioma

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with an intracranial WHO Grade 3 meningioma or lower grade meningioma that has progressed to WHO grade 3 that have received prior radiation therapy. Resected tissue must demonstrate: (a) RB positivity on immunohistochemistry (IHC); or, no RB mutations on next-generation sequencing (NGS). A washout period of 14 to 35 days is required between end of RT and Day 1 and must be fully recovered from the acute effects of RT. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable). Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Participant must be willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures. Age ≥18 years at time of consent. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale. Ability to swallow oral medications. Participant has adequate bone marrow and organ function Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause. For females of reproductive potential: use of highly effective contraception during study participation and for an additional 3 weeks after the end of treatment administration. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 3 weeks after the end of treatment administration. Exclusion Criteria: Prior history of cancer with ongoing treatment of disease. Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed. Pregnancy, breastfeeding or lactation. Known allergic reactions to components of the abemaciclib. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis. Known active systemic bacterial infection, fungal infection, or detectable viral infection . Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. Prior therapy with any CDK4/6 inhibitor. Treatment with another investigational drug within 5 half-lives of the investigational product. The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment (Abemaciclib)<br>Administered twice daily on days 1-28 of each 28-day cycle. | Drug: Abemaciclib<br>* Tablet<br>|
| Placebo Comparator: Placebo<br>Administered twice daily on days 1-28 of each 28-day cycle. | Drug: Placebo<br>* Tablet<br>* Other names: Abemaciclib placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression free survival (PFS24) rate measured from the time of surgery to date of recurrence | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug-related toxicity | Incidence of drug-related toxicity | Up to 30 days after last study dose | 
| Adverse Events | Number of adverse events through study completion | Up to 30 days after last study dose | 
| Deaths | Number and incidence of deaths | 24 months | 
| Incidence of clinical laboratory abnormalities per CTCAE | Clinical laboratory abnormalities per CTCAE | Up to 30 days after last study dose | 
| Progression-free survival in participants | 12 month progression-free survival (PFS12) rate measured from the time of surgery to date of recurrence. | 12 months | 
| Overall Survival | Overall survival at 24 months | 24 months | 
| Median Overall Survival | Median overall survival | 5 years |