Abemaciclib + Bevacizumab for Recurrent Brain Cancer

Overseen By Shanda Grant

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Bevacizumab, Abemaciclib, CDK4/6 inhibitors, VEGF agents

Disqualifiers: Uncontrolled hypertension, Diabetes, Cardiac failure, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: up to 2 years

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Describe the safety and adverse events associated with Abemaciclib 150 mg orally twice daily when administered with Bevacizumab 10 mg/kg intravenously every 2 weeks to recurrent GBM patients with specific tumor molecular aberrations

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain treatments are prohibited, so it's best to discuss your current medications with the trial team.

Is the combination of Abemaciclib and Bevacizumab safe for treating recurrent brain cancer?

Bevacizumab, also known as Avastin, has been used for treating recurrent high-grade gliomas (a type of brain cancer) and is generally considered safe, though it may not improve overall survival. It has been approved in several countries for this purpose, indicating a recognized safety profile in humans. ^{1 2 3 4 5}

How is the drug combination of Abemaciclib and Bevacizumab unique for treating recurrent brain cancer?

The combination of Abemaciclib and Bevacizumab is unique because it targets both cell division and blood vessel growth in tumors. Abemaciclib inhibits proteins that help cancer cells divide, while Bevacizumab blocks a protein called VEGF that tumors use to grow new blood vessels, potentially improving treatment effectiveness for recurrent brain cancer. ^{3 4 5 6 7}

What data supports the effectiveness of the drug combination Abemaciclib and Bevacizumab for recurrent brain cancer?

Bevacizumab has shown promising results in treating recurrent glioblastoma, a type of brain cancer, by targeting and neutralizing VEGF, a protein that helps tumors grow blood vessels. Studies have reported improved survival rates in patients with recurrent glioblastoma when treated with Bevacizumab. ^{3 4 5 6 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent glioblastoma brain tumors, who have specific genetic changes in their tumor. They must be able to take oral meds, have good organ function, and a performance status of at least 60%. Women of childbearing age and men with partners must use contraception.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

I had surgery recently for a returning or worsening tumor and meet certain conditions.

I have used Novo-TTF therapy before but stopped before joining this study.

Exclusion Criteria

You have a condition that makes you bleed easily or affects your blood's ability to clot.

You have had bleeding in your brain recently as shown on a recent MRI.

I haven't had major blood vessel problems in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Participants receive Abemaciclib 150 mg orally twice daily with Bevacizumab 10 mg/kg intravenously every 2 weeks for 2 cycles to assess safety and adverse events

4 weeks

2 visits (in-person)

Treatment

Participants continue treatment with Abemaciclib and Bevacizumab for additional cycles

up to 2 years

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Bevacizumab

Trial Overview The trial tests the safety and side effects of Abemaciclib taken orally twice daily combined with Bevacizumab given intravenously every two weeks in patients whose glioblastoma has returned and shows certain molecular abnormalities.

How Is the Trial Designed?

Group I: Safety Run-In Experimental Treatment 2 Interventions

Abemaciclib 150 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles

Group II: Abemaciclib with Bevacizumab Experimental Treatment 2 Interventions

Abemaciclib 100 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles

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?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Edward Pan

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

Bevacizumab, a monoclonal antibody that targets VEGF, has shown promising results in treating recurrent glioblastoma multiforme (GBM), with notable response rates and progression-free survival at 6 months in various studies.

While early trials indicate that some patients may survive beyond 1 or 2 years on bevacizumab, definitive Phase III trial data are still needed to confirm its efficacy, and it is currently being tested in combination with other treatments for newly diagnosed GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in glioblastoma multiforme. Specenier, P.[2015]

Bevacizumab, an antiangiogenic agent approved in Canada for recurrent glioblastoma, represents a significant advancement in treatment options for this aggressive brain tumor, which typically has a poor prognosis despite initial therapies.

The review discusses how bevacizumab is being used in clinical practice in Canada, along with ongoing debates regarding its effectiveness and application in glioblastoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in recurrent glioblastoma: five informative patient scenarios. Mason, WP.[2016]

In a study of 27 patients with recurrent high-grade gliomas, bevacizumab demonstrated a clinical benefit rate of 59%, with a median progression-free survival (PFS) of 4.3 months and a six-month PFS rate of 43%.

The safety profile included some serious adverse events, with 10 episodes of grade 3/4 side effects, but overall, the efficacy and safety of bevacizumab were found to be comparable to other international studies on similar patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. Sahebjam, S., Garoufalis, E., Guiot, MC., et al.[2019]

A study of 310 glioblastoma patients from 2010 to 2014 found that the use of bevacizumab did not improve overall survival compared to patients treated before its approval, with median survival remaining similar at 13.5 months for IDH wild-type tumors.

However, patients receiving bevacizumab experienced a significant reduction in corticosteroid use during second-line treatment, suggesting a potential clinical benefit in managing treatment side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. Gramatzki, D., Roth, P., Rushing, EJ., et al.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in glioblastoma multiforme. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in high-grade gliomas: past, present, and future. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in recurrent glioblastoma: five informative patient scenarios. [2016]

5. China pubmed.ncbi.nlm.nih.gov

Antiangiogenic therapy with bevacizumab in recurrent malignant gliomas: analysis of the response and core pathway aberrations. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Bevacizumab use for recurrent high-grade glioma at McGill University Hospital. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study. [2020]

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

Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. [2022]