Abemaciclib (LY2835219) in Patients With Recurrent Primary Brain Tumors

NCT03220646 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 17-261
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to test any good and bad effects of a study drug called abemaciclib (LY2835219) in patients with recurrent brain tumors.

Conditions

Brain Tumor

Keywords

Abemaciclib (LY2835219); meningioma; Astrocytoma; ependymoma; Oligodendroglioma; CNS lymphoma; 17-261

Outcome Measures

Primary Outcomes (2)

• radiographic response rate

  MRI (or CT) scan by RANO criteria.

  6 months

• progression free survival (PFS)

  will be estimated by the Kaplan Meier method

  6 months

Study Arms (3)

A:recurrent IDH wildtype RB1 intact grade II and III gliomas

EXPERIMENTAL

The main study cohort will consist of patients with recurrent IDH wildtype, RB1 wildtype, WHO grade II and III gliomas that have failed previous therapy. This arm is currently on hold.

Drug: abemaciclib

B:Recurrent glioma any grade

EXPERIMENTAL

Ten patients who require standard of care cytoreductive surgery for recurrent astrocytoma, oligodendroglioma, or glioblastoma, will be offered pre-surgical abemaciclib and then resume the drug following recovery from surgery, continuing until disease progression or unacceptable toxicity analogous to the non-surgical patients in cohort A and C. This arm is closed to accrual.

Drug: abemaciclib

C:All other recurrent brain tumors

EXPERIMENTAL

This is an exploratory cohort including patients with recurrent IDH mutant glioma, meningioma, recurrent ependymoma, and recurrent PCNSL,and other primary brain tumors.

Drug: abemaciclib

Interventions

abemaciclib DRUG

abemaciclib 200mg PO q12 hours (+/- 2 hours) on days 1-28 of each 28 day cycle.

A:recurrent IDH wildtype RB1 intact grade II and III gliomas; C:All other recurrent brain tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed IDHwt, RB intact, grade II or III glioma that has recurred after first line therapy (consisting of at least maximum feasible surgical resection and radiation therapy). There is no limit on the number of prior therapies or types of therapies patients can have received.
• Measurable disease on imaging (1cm) or measurable non-enhancing tumor.
• At least 12 weeks elapsed since prior radiotherapy
• Patients with histologically confirmed glioma of any grade (II-IV) who are planned for a standard of care surgical debulking/resection and for whom participation in this study would not cause a medically unacceptable delay in surgery.
• Patients must have relapsed/progressed following therapy (consisting of at least maximum feasible surgical resection and radiation therapy).
• Histologically confirmed PCNSL that has recurred after prior methotrexate-based chemotherapy or for whom methotrexate-based chemotherapy is deemed medically not in the patient's best interest.
• Glioma patients:
• Standard of care next generation sequencing via a CLIA certified platform must be available, or planned and at a minimum include IDH, and RB status.
• All cohorts:
• Patients must provide written informed consent prior to any screening procedures.
• Age 18 years or older.
• KPS ≥ 60
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Patient is able to swallow and retain oral medication
• Required baseline laboratory status:

You may not qualify if:

• No limit on number of prior therapies
• Evidence of significant intracranial hemorrhage
• No other investigational or standard anti-tumor therapy allowed
• Patients must not have a known history of allergic reactions attributed to compounds of similar chemical or biologic composition.
• Patients must not have a serious preexisting medical condition(s) or uncontrolled intercurrent illness that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who have a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological original (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. This applies only to patients who have a documented history of HIV; HIV testing is not otherwise required.
• Have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies)
• Patients must not be on EIAEDs
• Females who are pregnant or lactating
• Must abstain from grapefruit juice
• Patients must not have other active concurrent malignancy
• Concurrent treatment on another clinical trial. Supportive care trials or non-therapeutic trials (i.e. Quality of life) are allowed.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Eli Lilly and Company: collaborator

Study Sites (8)

Hartford Healthcare Cancer Institute @ Hartford Hospital (Data collection only)

Hartford, Connecticut, 06102, United States

Location

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Publications (1)

• Kaley TJ, Grommes C, Coffee E, Young RJ, Morrison T, Daher A, Schaff LR, Deng Y, Nandakumar S, Diamond EL, DeAngelis LM, Panageas KS, Gavrilovic I, Lin A, Pentsova E, Stone J, Santomasso BD, Piotrowski AF, Nair S, Schultz N, Reiner AS, Mellinghoff IK. Multicenter basket trial for Central Nervous System tumors identifies activity of the CDK4/6 inhibitor abemaciclib in recurrent meningioma. Neuro Oncol. 2025 Aug 16:noaf184. doi: 10.1093/neuonc/noaf184. Online ahead of print.

  PMID: 40842355 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Meningioma; Astrocytoma; Ependymoma; Oligodendroglioma

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial

Study Officials

• Thomas Kaley, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, non-randomized, phase II trial of single-agent abemaciclib administered at previously defined MTD/RP2D in three cohorts of patients with primary brain tumors.

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 18, 2017
• Study Start: July 13, 2017
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 9, 2025

Record last verified: 2025-07

Locations

US (8)