Abemaciclib in Newly Diagnosed Meningioma Patients

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Meningioma
• Intervention / Treatment: Drug: Placebo; Drug: Abemaciclib

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ivy Research Navigator; Phone Number: 602-406-8605; Email: research@ivybraintumorcenter.org

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
      • Contact: Navigator; Phone Number: 602-406-8605; Email: research@ivybraintumorcenter.org
      • Principal Investigator: Nader Sanai, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Deaths	Number and incidence of deaths	24 months
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
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

Collaborators and Investigators

• Sponsor: Nader Sanai
• Collaborators: Eli Lilly and Company; Barrow Neurological Institute; Ivy Brain Tumor Center
• Investigators: Principal Investigator: Nader Sanai, MD, Ivy Brain Tumor Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2024
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 4, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Meningioma
• Other Study ID Numbers: 2021-14; 23-500-352-34-38 (Other Identifier: St. Joseph's Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No