A Study of Abemaciclib in Recurrent Glioblastoma

NCT02981940 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-383
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is studying a targeted therapy as a possible treatment for recurrent glioblastoma (GBM). The following intervention will be used in this study:

• Abemaciclib

Conditions

Glioblastoma

Keywords

Brain Tumor

Outcome Measures

Primary Outcomes (2)

• Intratumoral Abemaciclib Concentration

  Intratumoral abemaciclib concentration defined as the mean tumor-to-plasma ratio in contrast enhancing tissue. Patients were treated with abemaciclib prior to surgery. Tissue and plasma for analysis of this endpoint were obtained at the time of surgery.

  Single time point for each participant for collection of tissue and blood at surgery

• 6-Month Progression Free Survival (PFS6)

  The primary endpoint for the nonsurgical cohort was six-month progression free survival (PFS6). Progression is defined by Response Assessment in Neuro-Oncology criteria for high-grade glioma (RANO-HGG) as \> 25% increase in sum of the products of perpendicular diameters of enhancing lesions (over best response or baseline if no decrease) on stable or increasing doses of corticosteroids AND/OR one or more of the following: significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids steroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events (radiation therapy, demyelination, ischemic injury, infection, seizures, post-operative changes, or other treatment effects); any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor; or failure to return for evaluation due to death or deteriorating condition.

  6 months

Secondary Outcomes (7)

• pRB Expression Level of Tumor Tissue

  2 years

• Incidence of Treatment-Emergent Adverse Events

  2 years

• Area Under the Plasma Concentration Versus Time Curve (AUC)

  4 months

• Peak Plasma Concentration (Cmax)

  4 months

• Radiographic Response Rate

  2 years

Study Arms (3)

Abemaciclib with Surgery

EXPERIMENTAL

* Abemaciclib will be administered on a continuous twice daily dosing schedule * Patients who require re-operation will receive a short preoperative course of Abemaciclib * Tissue will be used to investigate the ability of Abemaciclib to pass through the blood brain barrier. * After recovery from surgery, participants will resume Abemaciclib. Each cycle lasts 28 days. * NOTE: enrollment to this arm is complete

Drug: Abemaciclib; Procedure: Surgery

Abemaciclib without Surgery

EXPERIMENTAL

* Abemaciclib will be administered on a continuous twice daily dosing schedule. Each Cycle last 28 days. * NOTE: enrollment to this arm is complete

Drug: Abemaciclib

Cohort 1 Surgery Arm

EXPERIMENTAL

Participants who require reoperation will be treated with abemaciclib for 10-14 days prior to surgery. Tissue will be used to further investigate the abilities of Abemaciclib. After surgery participants will come off study and pursue standard of care treatments at their treating physician's discretion.

Drug: Abemaciclib; Procedure: Surgery

Interventions

Abemaciclib DRUG

Abemaciclib capsule

Also known as: LY2835219

Abemaciclib with Surgery; Abemaciclib without Surgery; Cohort 1 Surgery Arm

Surgery PROCEDURE

Surgery

Abemaciclib with Surgery; Cohort 1 Surgery Arm

Eligibility Criteria

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

You may qualify if:

• Participants must be able to understand and willing to sign a written informed consent document.
• Participants must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must be at least 18 years old on day of signing informed consent.
• Participants must have a Karnofsky Performance Status (KPS) ≥ 60
• Participants must be able to swallow capsules/tablets
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy of the trial are eligible.
• Nature of illness and treatment history
• Participants must undergo central pathology review to histologically confirm the diagnosis of glioblastoma, IDH-wildtype; glioblastoma variants; or astrocytoma, IDH-mutant, WHO grade 4 (1 unstained slide or 1 H\&E slide must be submitted to and reviewed by a pathologist at the DFCI Coordinating Center prior to enrollment of the participant for central pathology review).
• To be eligible for the study all participants (Cohort 1 and 2) are required to provide genomic profiling data from assays performed in a CLIA-certified lab. A sequencing-based assay is required and must include reporting of the RB1 gene in explicit terms within the report. Only sequencing assays that include coverage of all exons of the RB1 gene are able to be utilized (most commonly called a targeted exome assay; e.g. Oncopanel, Impact, FoundationOne). In addition, patients must provide a report of copy assessment which reports status of RB1. The reporting may be from a copy array (ideally Oncoscan SNP array or Agilent array CGH) or can also be from sequencing assay if copy status is explicitly provided with quantitative information regarding the status of relevant genes. Specifically, the reporting should provide the following information with respect to relevant biomarkers required for enrollment to the study as listed below.
• Results from genomic profiling must be sent to the DFCI Coordinating Center prior to enrollment of the participant for central pathology review.
• Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence for more than single copy loss for any of the genes defined as array CGH/SNP log2 ratio of \<0.3 by array CGH; or from sequencing data with sufficient coverage for evaluation). Rearrangement/evidence or intragenic breaks by copy or sequencing assay also will be considered eligible for study (any copy status).
• CDK4 or CDK6 high-level amplification. (The amplicon size must be \<10Mb and the magnitude the gain must be log2 ratio \>1.5 or estimated as \>10 copies).
• AND
• Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations by sequencing).
• Participants must be at first relapse of GBM. Relapse is defined as progression following initial therapy (i.e. radiation+/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 1 prior therapy (initial treatment). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse.

You may not qualify if:

• Pathology
• Prior evidence of 1p/19q co-deletion.
• IDH1/2 mutation in any prior biopsy.
• Previous therapies
• Participants who have received prior treatment with a CDK4/6 inhibitor.
• Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL184, sunitinib etc).
• Concomitant medications
• Participants taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine, rufinamide, and felbamate. Participants must be off any EIAEDs for at least 14 days prior to starting study drug. A list of EIAEDs and other inducers of CYP3A4 can be found.
• Participants taking a drug known to be a strong inhibitor or inducer of isoenzyme CYP3A . Participant must be off CYP3A inhibitors and inducers for at least 14 days prior to starting study drug. NOTE: participants must avoid consumption of Seville oranges (and juice), grapefruits or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period due to potential CYP3A4 interaction.
• Participants receiving any other investigational agents.
• Current use of herbal preparations/medications, including but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng. Participants should stop using these herbal medications 7 days prior to first dose of study drug.
• Current use of warfarin sodium or any other coumadin-derivative anticoagulant. Participants must be off Coumadin-derivative anticoagulants for at least 7 days prior to starting study drug. Low molecular weight heparin is allowed.
• Requires treatment with high dose systemic corticosteroids defined as dexamethasone \> 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of registration.
• Other illnesses
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (7)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0372, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

UT, M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

abemaciclib; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Eudocia Q Lee, MD MPH
• Organization: Dana-Farber Cancer Institute

eudocia_lee@dfci.harvard.edu

617.632.2166

Study Officials

• Eudocia Q Lee, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MPH

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: December 5, 2016
• Study Start: February 9, 2017
• Primary Completion: June 30, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 2, 2025
• Results First Posted: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)