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

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a phase II, single arm, open label study looking how well a drug called abemaciclib works in patients with recurrent oligodendroglioma

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.

What makes the drug Abemaciclib unique for treating brain cancer?

Abemaciclib is unique because it can cross the blood-brain barrier more efficiently than similar drugs, potentially allowing it to target brain tumors more effectively. It is an oral drug that inhibits specific proteins (CDK4 and CDK6) involved in cell growth, which may help slow down or stop the growth of brain cancer cells. ^{1 2 3 4 5}

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 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]

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 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]

Citations

1. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]

3. United States 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. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. [2019]