Abemaciclib for Brain Cancer

Not currently recruiting at 9 trial locations

Overseen By Ingo Mellinghoff, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antiretrovirals, EIAEDs

Disqualifiers: Intracranial hemorrhage, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called abemaciclib to determine its effects on recurrent brain tumors. Researchers aim to discover if abemaciclib can halt or slow the growth of tumors, including gliomas and meningiomas. Individuals with recurrent brain tumors after standard treatments and specific tumor types may qualify. Participants must adhere to a treatment plan and undergo imaging tests to monitor progress. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that no other investigational or standard anti-tumor therapy is allowed. Additionally, patients must not be on enzyme-inducing antiepileptic drugs (EIAEDs) and must abstain from grapefruit juice.

Is there any evidence suggesting that abemaciclib is likely to be safe for humans?

Research has shown that abemaciclib has been tested for safety in various cancers, including brain tumors. In earlier studies, many patients tolerated the drug well, with common side effects including tiredness, diarrhea, and low white blood cell counts. Serious side effects were less common.

Another study on abemaciclib for brain conditions found that researchers could safely measure the drug in brain tumors. This allowed them to track how much of the drug reached the brain without causing major issues.

Since this trial is in the middle stage (Phase 2), it indicates that abemaciclib has demonstrated a reasonable level of safety in earlier research. However, individual reactions can vary. Always consult a doctor when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Unlike the standard treatments for brain cancer, which often include surgery, radiation, and chemotherapy, Abemaciclib offers a unique approach by targeting specific proteins called cyclin-dependent kinases (CDK4 and CDK6). These proteins play a critical role in cell division, and by inhibiting them, Abemaciclib can potentially slow down or stop the growth of cancer cells. Researchers are excited about Abemaciclib because it allows for a more targeted intervention, which could lead to better outcomes and fewer side effects compared to traditional chemotherapy. Additionally, its ability to cross the blood-brain barrier makes it a promising option for treating brain tumors, something that many existing drugs struggle to achieve.

What evidence suggests that abemaciclib might be an effective treatment for brain cancer?

Research suggests that abemaciclib may help treat certain brain tumors. This trial will explore its effectiveness across various treatment arms. Studies have shown that abemaciclib can enter the brain, which is crucial for treating brain cancer. In some research, abemaciclib was tested with other drugs and showed promise in killing cancer cells. Additionally, past studies indicated that abemaciclib might be effective when other treatments have failed, especially in hard-to-treat brain cancers like glioblastoma. Overall, while more information is needed, early findings suggest abemaciclib could be effective for some recurring brain tumors. ^{2 3 6 7}

Who Is on the Research Team?

Thomas Kaley, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with recurrent brain tumors, specifically IDH wildtype and RB intact gliomas or other primary brain tumors. Participants must have had prior therapy, be able to swallow pills, consent to use birth control, and not be on certain medications or have specific health conditions that could interfere with the study.

Inclusion Criteria

You are expected to live for more than 8 weeks.

My brain tumor has returned despite treatment and is IDH mutant.

My glioma has been or will be tested for specific genetic changes.

Exclusion Criteria

I have had multiple treatments for my condition.

You cannot drink grapefruit juice while participating in the study.

I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib for recurrent brain tumors, with some patients undergoing pre-surgical treatment

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview

The trial is testing abemaciclib (LY2835219) effects on patients with recurrent brain tumors. It aims to understand both the potential benefits and adverse reactions of this drug in individuals who have seen their tumor return after initial treatment.

How Is the Trial Designed?

Group I: C:All other recurrent brain tumors Experimental Treatment 1 Intervention

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

Group II: B:Recurrent glioma any grade Experimental Treatment 1 Intervention

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.

Group III: A:recurrent IDH wildtype RB1 intact grade II and III gliomas Experimental Treatment 1 Intervention

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.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Abemaciclib, a CDK4 and CDK6 inhibitor, shows significantly better brain penetration compared to palbociclib, making it a promising candidate for treating primary brain tumors like glioblastoma.

In preclinical models, abemaciclib not only increased survival in rats with brain tumors but also demonstrated additive effects when combined with the standard treatment temozolomide, suggesting its potential as an effective therapy for brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft. Raub, TJ., Wishart, GN., Kulanthaivel, P., et al.[2019]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

Abemaciclib has demonstrated promising clinical activity in patients with relapsed mesothelioma that is deficient in the p16ink4A protein, suggesting it may be an effective treatment option for this specific cancer type.

The findings indicate a potential new therapeutic avenue for mesothelioma patients, particularly those whose tumors lack the p16ink4A protein, which is often associated with tumor suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibition Shows Clinical Activity in p16ink4A-Deficient Mesothelioma. [2022]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02981940

A Study of Abemaciclib in Recurrent Glioblastoma

In this research study, the investigators are looking to see how safe and effect Abemaciclib is with the participant type of cancer. In the surgical ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12202147/

Potential synergism of abemaciclib with chloroquine and ...

This case highlights the combination of abemaciclib with chloroquine and disulfiram/copper as a prospective novel salvage therapy for recurrent atypical ...

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clinicalstudies.info.nih.gov

clinicalstudies.info.nih.gov/protocoldetails.aspx?id=22-C-0003&&query=

Protocol Details

Researchers want to see if an anticancer drug (abemaciclib) can help. Objective: To see if researchers can measure how much abemaciclib is in a person's brain ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ...

The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02308020

NCT02308020 | A Study of Abemaciclib (LY2835219) in ...

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive ...

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aacrjournals.org

aacrjournals.org/clincancerres/article/26/20/5310/82934/A-Phase-II-Study-of-Abemaciclib-in-Patients-with

A Phase II Study of Abemaciclib in Patients with Brain ...

The primary objective was to evaluate intracranial objective response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM)

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cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01113

Abemaciclib for the Treatment of Patients with Recurrent ...

This phase I clinical trial investigates whether it is possible to safely measure how much of the anti-cancer drug, abemaciclib remains in the brain tumor ...