Abemaciclib for Glioblastoma

Not currently recruiting at 6 trial locations

Overseen By Amanda Spearman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CDK4/6 inhibitors, Anti-VEGF agents

Disqualifiers: 1p/19q co-deletion, IDH1/2 mutation, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called abemaciclib to determine its effectiveness in treating glioblastoma, an aggressive brain cancer that has recurred after treatment. The trial aims to assess abemaciclib's efficacy, particularly when taken before surgery or as a continuous treatment. This study may suit individuals whose glioblastoma has returned after initial treatment and who show clear signs of tumor progression on a recent MRI or CT scan. Participants must reliably take medication and have a diagnosis meeting specific genetic criteria. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications before starting the study drug. Specifically, you must stop taking enzyme-inducing anti-epileptic drugs, strong inhibitors or inducers of CYP3A, herbal medications like St. John's wort, and warfarin sodium at least 7 to 14 days before starting the study drug. You should discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Abemaciclib has been tested in people with recurring cancers, such as glioblastoma. Studies indicate that most patients tolerate it well. Common side effects include diarrhea and tiredness, which are usually manageable.

In past trials, serious side effects were less common. Pregnant or breastfeeding individuals should not use Abemaciclib, as it might affect the baby.

The FDA has already approved Abemaciclib for other conditions, providing some confidence in its safety. Doctors have used it with patients for a while and understand its effects well.

Overall, while some risks exist, previous studies suggest that Abemaciclib is relatively safe for use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for glioblastoma?

Unlike the standard treatments for glioblastoma, which often involve surgery, radiation, and chemotherapy, Abemaciclib offers a unique mechanism of action as a CDK4/6 inhibitor. This means it targets specific proteins involved in cancer cell division, potentially slowing tumor growth more effectively. Researchers are particularly excited because Abemaciclib can cross the blood-brain barrier, a significant challenge for many drugs, allowing it to directly reach and act on the brain tumor. Additionally, Abemaciclib's continuous dosing schedule offers a novel approach that may improve outcomes for patients who require reoperation.

What evidence suggests that Abemaciclib might be an effective treatment for glioblastoma?

Research has shown that abemaciclib might help treat recurrent glioblastoma by slowing its growth or even shrinking it. In this trial, some participants will receive abemaciclib alone, while others will receive it in combination with surgery. Early results indicated that patients taking abemaciclib experienced longer periods without cancer worsening compared to others. Specifically, the risk of cancer progression was reduced by 33%, marking a significant improvement. Abemaciclib was generally well-tolerated, with most people not experiencing new or unexpected side effects. This targeted therapy interferes with cancer cell growth, offering hope for those with aggressive brain tumors. ^{1 4 6 7 8}

Who Is on the Research Team?

Eudocia Q Lee, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with recurrent glioblastoma who can take oral medication and adhere to the study schedule. They must have specific genetic markers (CDK4/6 amplification, wild-type RB status), a Karnofsky Performance Status of at least 60, and be able to provide tissue samples for research. Women must test negative for pregnancy and agree to contraception; men also need to use birth control.

Inclusion Criteria

Participants must be able to understand and willing to sign a written informed consent document

I have another cancer, but it won't affect this trial's treatment.

Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan

Exclusion Criteria

I have been treated with drugs targeting VEGF.

Participants who are pregnant or breastfeeding

I am currently taking certain medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0 Treatment

Participants receive a few small doses of Abemaciclib to assess its ability to reach the brain tumor

10-14 days

1 visit (in-person)

Phase II Treatment

Participants receive Abemaciclib on a continuous twice daily dosing schedule, each cycle lasts 28 days

4 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Surgery

Trial Overview The trial is testing Abemaciclib, a targeted therapy drug, on patients with recurrent glioblastoma after surgery. The aim is to see if this drug can effectively treat the cancer by focusing on certain genetic characteristics of the tumor cells.

How Is the Trial Designed?

Group I: Cohort 1 Surgery Arm Experimental Treatment 2 Interventions

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.

Group II: Abemaciclib without Surgery Experimental Treatment 1 Intervention

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

Group III: Abemaciclib with Surgery Experimental Treatment 2 Interventions

* 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

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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 2 study involving 39 patients with recurrent grade III malignant glioma, the combination of imatinib mesylate and hydroxyurea showed a 24% progression-free survival rate at 6 months, indicating some efficacy in this challenging condition.

The treatment was well tolerated, with serious side effects occurring in less than 4% of cases, primarily hematologic, suggesting a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas. Desjardins, A., Quinn, JA., Vredenburgh, JJ., et al.[2018]

In a phase III clinical trial involving 325 patients with recurrent glioblastoma, cediranib did not significantly improve progression-free survival compared to lomustine alone, whether used as a monotherapy or in combination.

Despite not meeting the primary endpoint, cediranib demonstrated some clinical benefits in secondary outcomes, such as delaying neurological deterioration and reducing the need for corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. Batchelor, TT., Mulholland, P., Neyns, B., et al.[2022]

In a phase II study involving 33 patients with recurrent glioblastoma, dovitinib did not show efficacy in prolonging progression-free survival (PFS) at 6 months, with only 12% in the anti-angiogenic naïve group achieving this compared to 0% in the pretreated group.

The study revealed significant toxicity, with 67% of patients experiencing grade 3 toxicities and 15% experiencing grade 4 toxicities, indicating that while dovitinib was not effective, it did pose safety concerns for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of Dovitinib in recurrent glioblastoma. Sharma, M., Schilero, C., Peereboom, DM., et al.[2020]

In a phase I study involving patients with newly diagnosed glioblastoma, the maximum tolerated dose (MTD) of buparlisib when combined with temozolomide was determined to be 80 mg/day, but the MTD for the combination with both temozolomide and radiotherapy could not be established due to significant dose-limiting toxicities.

The study reported high rates of adverse events, particularly nausea and fatigue, leading to treatment discontinuations, which contributed to Novartis's decision to halt further development of buparlisib for this indication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Wen, PY., Rodon, JA., Mason, W., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02981940

A Study of Abemaciclib in Recurrent Glioblastoma This research study is a Phase 0/II clinical trial. Phase 0 clinical trials use only a few small doses of a drug. Phase II clinical trials test the safety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650442/

A PHASE II PLATFORM TRIAL USING BAYESIAN ... Preliminary analysis suggests that abemaciclib increases PFS compared to control. Updated toxicity, PFS and survival data and potential genomic biomarker ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01394016

NCT01394016 | A Phase 1 Study of LY2835219 In ... The purpose of this study is to determine a safe dose of Abemaciclib to be given to participants with advanced cancer and to determine any side effects that ...

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

Abemaciclib for the Treatment of Patients with Recurrent ... Giving abemaciclib to patients with recurrent high grade gliomas may prevent high grade gliomas from growing, slow down their growth, or possibly shrink them.

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.2014

Preliminary results of the abemaciclib arm in ... Abemaciclib was generally well-tolerated with no new toxicity signals identified. PFS was significantly longer (HR 0.67; p = 0.03, logrank test) ...

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

Protocol Details Data on fetal outcomes and breastfeeding are to be collected for regulatory reporting and drug safety evaluation. -Abemaciclib administration must be able to ...

7. trials.braintumor.org trials.braintumor.org/trials/NCT03220646

Abemaciclib (LY2835219) in Patients With Recurrent Primary ... If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome ...

8. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/26/20/5310/2063071/5310.pdf

A Phase II Study of Abemaciclib in Patients with Brain ... Descriptive statistics summarized safety data. All tests assumed a two-sided. 0.05 alpha, and CIs assumed a two-sided 95% level. Analyses were conducted with ...