Abemaciclib for Brain Cancer

Overseen By Timothy Prior, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stephen Bagley, MD, MSCE

Must not be taking: Enzyme-inducing antiepileptics

Disqualifiers: Pregnancy, Active infections, Cardiovascular history, 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: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a drug called abemaciclib for individuals with recurrent oligodendroglioma, a type of brain cancer. It specifically targets those whose cancer has returned or worsened after treatments such as radiation and certain chemotherapies. Participants must have a confirmed diagnosis of oligodendroglioma that has recurred after these treatments and must be able to take oral medication. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain anti-epileptic drugs like carbamazepine, phenytoin, and phenobarbitol. You also cannot take other cancer treatments while participating in this trial.

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

Research has shown that abemaciclib has been tested in patients with various types of cancer, including brain tumors. In these studies, abemaciclib demonstrated some effectiveness, although not all main goals were achieved. Importantly, patients generally tolerated it well.

In one study, patients experienced some side effects, but these were often manageable. Common side effects included diarrhea and tiredness. These side effects resemble those seen with other cancer treatments and did not prevent most patients from continuing the therapy.

The current study phase indicates that researchers have tested abemaciclib in humans for safety, but its effectiveness and any potential risks are still under close observation. Trials regularly monitor participants to ensure their well-being, and any new information about side effects is taken seriously to protect their health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abemaciclib is unique because it specifically targets enzymes called CDK4 and CDK6, which are involved in cell division. This precision makes it different from traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, often leading to more side effects. Researchers are excited about Abemaciclib for brain cancer because it has shown potential to penetrate the blood-brain barrier, a significant challenge for many cancer drugs, allowing it to act directly on brain tumors. These features suggest it could offer a more targeted and potentially less toxic treatment option for brain cancer patients.

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

Research has shown that abemaciclib may help treat certain brain cancers. In patients with cancer that has spread to the brain, abemaciclib improved disease control and extended survival compared to past data. Studies on recurring brain tumors have also reported potential benefits of this treatment. Although the drug is mainly used for other types of cancer, these findings suggest it might help manage brain cancer, such as oligodendroglioma, by slowing tumor growth. Participants in this trial will receive abemaciclib as a single treatment arm to evaluate its effectiveness in brain cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Stephen Bagley, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults with recurrent oligodendroglioma, confirmed by specific molecular markers (1p/19q codeletion), who have had prior radiation and chemotherapy can join. They must be able to take oral meds, have a life expectancy over 3 months, good performance status, and adequate organ function. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

My oligodendroglioma has worsened after radiation and chemotherapy.

My liver tests are within the required range for the study.

I have waited the required time after my last cancer treatment before joining this trial.

Exclusion Criteria

I do not have an active infection or HIV, and my hepatitis is not currently active.

I am not pregnant or breastfeeding.

Women must agree not to breast feed while on abemaciclib treatment and for at least three months following the last dose of study therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib 200mg tablet PO twice daily administered on 28-day cycles until tumor progression or unacceptable toxicity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after the end of treatment

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The trial is testing the effectiveness of abemaciclib at a dose of 200 MG in patients with recurrent oligodendroglioma. It's an open-label study where all participants receive the drug to see how well it works against this type of brain tumor.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

Abemaciclib 200mg tablet PO twice daily administered on 28-day cycles Subjects remain on treatment until tumor progression or unacceptable toxicity.

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?

Stephen Bagley, MD, MSCE

Lead Sponsor

Trials

2

Recruited

70+

Abramson Cancer Center at Penn Medicine

Collaborator

Trials

425

Recruited

464,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Abramson Cancer Center of the University of Pennsylvania

Collaborator

Trials

360

Recruited

108,000+

Published Research Related to This Trial

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, 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 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 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 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]

Citations

1. 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 ...

2. 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 ... In patients with LM, abemaciclib treatment was associated with disease control, and overall survival longer than expected, compared with historical controls.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12395139/

MBC treated with abemaciclib and local intracranial therapy Overall, the majority of patients (80.5%) received treatment to the brain (radiation or surgery) after brain metastasis diagnosis and before ...

4. trials.braintumor.org trials.braintumor.org/trials/NCT03220646

Abemaciclib (LY2835219) in Patients With Recurrent Primary ... 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.

5. 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.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32694159/

A Phase II Study of Abemaciclib in Patients with Brain ... Conclusions: This study did not meet its primary endpoint. Abemaciclib was associated with an iCBR of 24% in patients with heavily pretreated HR ...

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

Protocol Details Based on the results of abemaciclib levels in the brain, participants may keep taking abemaciclib and another drug (temozolomide) by mouth until their cancer ...