A Phase 2 Study of Abemaciclib in Patients With Recurrent Primary Brain Tumors

Memorial Sloan Kettering Cancer Center8 sites in 1 country64 target enrollmentJuly 13, 2017

ConditionsBrain Tumor

Interventionsabemaciclib

Drugsabemaciclib

Overview

Phase: Phase 2
Intervention: abemaciclib
Conditions: Brain Tumor
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 64
Locations: 8
Primary Endpoint: radiographic response rate
Status: Active, not recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 13, 2017

End Date

July 1, 2026

Last Updated

9 months ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Cohort A specific inclusion:
•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
•Cohort B specific inclusion:
•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).
•Cohort C specific Inclusion:
•Histologically confirmed IDH mutant glioma, meningioma, schwanomma, PCNSL, ependymoma, or other Primary Brain Tumors that have recurred despite previous standard of care therapy. Because this cohort is, in part, meant to allow patients access to therapy who might not otherwise be eligible for other clinical trials - deviations from standard of care treatment or histological confirmation can be presented to and approved by the Principal Investigator for inclusion in the study.
•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.

Exclusion Criteria

•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

Arms & Interventions

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

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.

Intervention: abemaciclib

B:Recurrent glioma any grade

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.

Intervention: abemaciclib

C:All other recurrent brain tumors

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

Intervention: abemaciclib