Abemaciclib for Glioblastoma

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

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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

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.

How is the drug Abemaciclib unique for treating glioblastoma?

Abemaciclib is unique for treating glioblastoma because it is a CDK4/6 inhibitor, which means it targets specific proteins (CDK4 and CDK6) that help cancer cells grow and divide, offering a different approach compared to other treatments that focus on DNA damage or blood vessel growth. ^{1 2 3 4 5}

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

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

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

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

Exclusion Criteria

I have been treated with drugs targeting VEGF.

I am currently taking certain medications.

Participants who are pregnant or breastfeeding

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 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 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 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. United States 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. [2022]

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

Phase II study of Dovitinib in recurrent glioblastoma. [2020]

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

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas. [2018]

4. England 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. [2021]

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

ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy. [2022]