Abemaciclib + Bevacizumab for Recurrent Brain Cancer

(SCCC-06319 Trial)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, Abemaciclib (a cancer treatment) and Bevacizumab (an anti-angiogenic drug), to determine their safety and identify any side effects in people with recurrent brain cancer, specifically glioblastoma (GBM). The focus is on patients whose tumors have specific genetic changes, such as the loss or gain of certain genes. Those with recurrent GBM after initial treatment and confirmed genetic changes in their tumors might be suitable candidates. The trial aims to assess how well this drug combination controls cancer recurrence. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering a unique opportunity to contribute to groundbreaking cancer research.

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

Research shows that Bevacizumab, one of the drugs in this study, has been used to treat serious brain tumors like glioblastoma. Many patients tolerate it well, and safety data supports its use in these cases. Bevacizumab is generally considered safe, though some people may experience side effects.

Researchers are testing Abemaciclib to evaluate its effects on recurring brain tumors. Previous studies have examined both its benefits and side effects. However, it is still early in the research, so there is limited information on its safety when combined with Bevacizumab.

As this trial is in the early stages, it primarily focuses on safety. Researchers closely monitor any side effects or issues participants might experience. Those considering participation should know that safety is a top priority, and this trial aims to gather important information about the effectiveness of these drugs together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abemaciclib and Bevacizumab for treating recurrent brain cancer because it introduces a new approach compared to existing treatments. Abemaciclib is a CDK4/6 inhibitor, which works by targeting proteins that control cell division, potentially slowing down or stopping the growth of cancer cells. Bevacizumab, on the other hand, is an antibody that inhibits VEGF, a protein that helps tumors form new blood vessels, essentially cutting off their supply lines. While traditional treatments often focus on chemotherapy and radiation, this combination targets the cancer's growth mechanisms and blood supply pathways, which might improve outcomes for patients with brain cancer.

What evidence suggests that this trial's treatments could be effective for recurrent brain cancer?

This trial will evaluate the combination of Abemaciclib with Bevacizumab for treating recurrent brain cancer. Research shows that this combination might help treat recurring brain cancer. Earlier studies found that Bevacizumab can extend survival by about two months in some brain cancer cases. Abemaciclib stops cancer cells from growing, and this trial tests its effectiveness with Bevacizumab. The goal of this combination is to slow cancer growth by blocking specific pathways that help tumors grow. Although results are still early, there is hope that this combination will improve outcomes for patients with recurring glioblastoma. ^{2 6 7 8 9}

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, 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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02981940

A Study of Abemaciclib in Recurrent Glioblastoma In this research study, the investigators are looking to see how safe and effect Abemaciclib is with the participant type of cancer. In the surgical ...

2. 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04074785

NCT04074785 | Abemaciclib w/Bevacizumab in Recurrent ... Assess safety and adverse events associated with Abemaciclib 150 mg orally twice daily when administered with Bevacizumab 10 mg/kg intravenously every 2 weeks ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7594557/

Glioblastoma in adults: a Society for Neuro-Oncology (SNO ... They were shown to produce a modest survival advantage of approximately 2 months but are used only sporadically, in part because the efficacy data stem from the ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00385

Abemaciclib in Treating Patients with Recurrent Glioblastoma This phase II trial studies how well abemaciclib works in treating patients with glioblastoma that has come back after a period of improvement (recurrent).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04074785

NCT04074785 | Abemaciclib w/Bevacizumab in Recurrent ... Assess safety and adverse events associated with Abemaciclib 150 mg orally twice daily when administered with Bevacizumab 10 mg/kg intravenously every 2 weeks ...

7. dana-farber.org dana-farber.org/clinical-trials/16-383

A Phase 0/2 Study of Abemaciclib in Recurrent Glioblastoma This research study is studying a targeted therapy as a possible treatment for recurrent glioblastoma (GBM).

8. withpower.com withpower.com/trial/early-phase-1-glioblastoma-11-2019-e308e

Abemaciclib + Bevacizumab for 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, ...

9. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/glioblastoma

Glioblastoma Clinical Trials This study aims to evaluate the safety of local delivery of AMSCs for recurrent GBM by noting the incidence of adverse events, as well as radiological and ...