Atezolizumab + Bevacizumab + Memantine for Liver Cancer

((HCC) Trial)

Recruiting at 1 trial location

Overseen By Elahe Mollapour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inova Health Care Services

Must not be taking: Memantine

Disqualifiers: Childs-Pugh B/C cirrhosis, Pregnancy, HIV, 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

Compensation: Varies

Number of Visits: 8

Duration: 6 months

19 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for liver cancer, specifically hepatocellular carcinoma. Researchers aim to evaluate the effectiveness of a mix of three drugs—atezolizumab (an immunotherapy drug), bevacizumab (a targeted therapy drug), and memantine (a medication typically used for Alzheimer's disease)—in treating this cancer. It targets individuals with newly diagnosed, advanced liver cancer that cannot be surgically removed. Participants should have a stable health condition and be able to swallow pills. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are already on memantine, you cannot participate. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

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

Research has shown that the combination of atezolizumab and bevacizumab is generally well-tolerated by people with liver cancer. Studies have found that this combination helps patients live longer compared to some other treatments. It is considered safe for patients with certain liver conditions, such as cirrhosis, where the liver is scarred but still functions adequately.

Memantine, typically used for Alzheimer's disease, has not been used with these cancer drugs before, but it is known to be safe for its usual purpose.

As this study is in an early phase, researchers are still assessing the safety of this new combination. However, the other components of the treatment have been shown to be safe in humans so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab, bevacizumab, and memantine for liver cancer because it introduces memantine to the standard therapy. Unlike other treatments, which typically focus on immune modulation and blood vessel inhibition, memantine adds a novel approach by potentially protecting nerve cells and improving cognitive function. This combination might enhance the overall effectiveness of liver cancer treatment by offering a more comprehensive attack on the disease, potentially leading to better outcomes for patients.

What evidence suggests that this triplet therapy could be effective for liver cancer?

Research has shown that combining atezolizumab and bevacizumab effectively treats hepatocellular carcinoma, a type of liver cancer. Studies have found that this combination helps patients live longer and delays cancer progression. Real-world data also support these benefits, confirming the treatment's effectiveness in large patient groups. This trial adds memantine to the atezolizumab and bevacizumab regimen. The specific effects of this triple therapy are still under investigation, with the hope of achieving even better outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Arthur Winer, MD

Principal Investigator

Principal Investigator

Are You a Good Fit for This Trial?

This trial is for individuals with hepatocellular carcinoma, a type of liver cancer. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and have no conflicting conditions.

Inclusion Criteria

Patients must demonstrate the ability to understand and the willingness to sign a written informed consent document

I am eligible for this study regardless of my gender, race, ethnicity, or sexual orientation.

My cancer cannot be removed with surgery and is advanced.

Exclusion Criteria

I have pain from my cancer that isn't managed well.

I haven't had major surgery or a serious injury in the last 28 days.

My liver cancer is of a specific rare type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive triplet therapy with atezolizumab, bevacizumab, and memantine in 21-day cycles

6 months

8 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

• Atezolizumab, Bevacizumab
• Memantine

Trial Overview

The study investigates the combined effect of three drugs: Atezolizumab (an immunotherapy), Bevacizumab (a drug that inhibits blood vessel growth in tumors), and Memantine Hydrochloride (commonly used for Alzheimer's disease) on liver cancer.

How Is the Trial Designed?

Group I: Addition of Memantine to Atezolizumab and Bevacizumab (the current systemic standard of care) Experimental Treatment 3 Interventions

The study intervention consists of the use of the triplet therapy (atezolizumab, bevacizumab, and memantine) given in 21-day cycles over six months.

Who Is Running the Clinical Trial?

Inova Health Care Services

Lead Sponsor

Trials

80

Recruited

22,700+

Published Research Related to This Trial

The IMbrave150 study supports the use of atezolizumab and bevacizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC), indicating its efficacy in this patient population.

However, this combination therapy can lead to serious side effects, as demonstrated by a case of transverse myelitis occurring during treatment, highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Transverse Myelitis Following Treatment with Atezolizumab for Advanced Hepatocellular Carcinoma. Kim, KH., Baek, YH., Kang, YW., et al.[2023]

A 70-year-old woman with advanced hepatocellular carcinoma developed severe encephalitis after just one cycle of the combination therapy with atezolizumab and bevacizumab, highlighting a rare but serious adverse effect of this treatment.

Rapid immunosuppressive treatment with high-dose steroids and plasmapheresis led to clinical improvement in the patient's encephalitis, although she ultimately succumbed to progressive liver cancer, indicating the need for careful monitoring of neurological symptoms in patients receiving immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review. Özdirik, B., Jost-Brinkmann, F., Savic, LJ., et al.[2023]

In a phase 1b study involving 223 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab resulted in a significantly longer median progression-free survival of 5.6 months compared to 3.4 months for atezolizumab alone, indicating enhanced efficacy of the combination treatment.

The most common serious treatment-related adverse events included hypertension and proteinuria, with a treatment-related death rate of 3% in the combination group, suggesting that while the combination therapy is effective, it does carry some safety risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lee, MS., Ryoo, BY., Hsu, CH., et al.[2020]

Atezolizumab combined with bevacizumab demonstrated good efficacy in treating advanced hepatocellular carcinoma (HCC), with a pooled overall response rate of 26% and a median overall survival of 14.7 months based on a review of 23 studies involving 3168 patients.

The treatment was well-tolerated, with 83% of patients experiencing any grade adverse events, and 30% experiencing grade 3 or higher adverse events, indicating that while side effects are common, the combination therapy remains a viable first-line option for advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: a single-arm meta-analysis. Gao, X., Zhao, R., Ma, H., et al.[2023]

In a study of 1447 patients treated with tyrosine-kinase inhibitors for hepatocellular carcinoma, only 29% were eligible for the combination therapy of atezolizumab-bevacizumab based on the IMbrave-150 trial criteria, indicating limited real-world applicability.

Eligible patients showed a median overall survival of 14.9 months, which was longer than non-eligible patients, suggesting that those who meet the criteria have better baseline health and cancer characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. Stefanini, B., Bucci, L., Santi, V., et al.[2022]

The combination therapy of atezolizumab and bevacizumab shows potential as a treatment option for patients with both hepatocellular carcinoma and gastric adenocarcinoma.

This finding suggests a possible new approach for managing these concurrent cancers, although further studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. Suga, T., Kimura, Y., Furuya, K., et al.[2023]

Atezolizumab plus bevacizumab improves overall survival and quality-adjusted life-years (QALYs) compared to sorafenib in patients with unresectable or metastatic hepatocellular carcinoma, with an increase of 0.623 life-years and 0.484 QALYs in a hypothetical sample of 424 patients.

Despite the clinical benefits, the treatment is not cost-effective, with an incremental cost-effectiveness ratio (ICER) of $322,500 per QALY, indicating that significant price reductions of 37% to 47% for atezolizumab and bevacizumab would be necessary to make it a more viable option compared to sorafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma. Zhang, X., Wang, J., Shi, J., et al.[2021]

In a study of 766 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, those who met the IMbrave150 trial inclusion criteria had significantly longer overall survival (16.3 months) compared to those who did not (14.3 months).

Among patients who did not meet the IMbrave150 criteria, those with a better liver function (ALBI grade 1) experienced a notable survival benefit, with a median overall survival of 16.7 months compared to 5.9 months for those with ALBI grade 2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis? Rimini, M., Persano, M., Tada, T., et al.[2023]

In a phase 3 trial involving 501 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab significantly improved overall survival (67.2% at 12 months) and progression-free survival (6.8 months) compared to sorafenib.

The treatment with atezolizumab-bevacizumab showed a lower risk of death (hazard ratio 0.58) and similar rates of severe adverse events compared to sorafenib, indicating a favorable safety profile despite some instances of grade 3 or 4 hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. Finn, RS., Qin, S., Ikeda, M., et al.[2021]

This case report describes a 42-year-old woman with hepatocellular carcinoma who developed encephalitis after receiving atezolizumab and bevacizumab therapy, highlighting a potential serious immune-related adverse effect of these treatments.

Despite treatment with steroid pulse therapy leading to some improvement in symptoms, the patient continued to experience lasting effects, such as right-sided paralysis and aphasia, indicating that while the therapy can be effective, it may also carry significant risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced Encephalitis in a Patient with Hepatocellular Carcinoma: A Case Report and Literature Review. Satake, T., Maruki, Y., Kubo, Y., et al.[2022]

In a study of 191 patients with unresectable hepatocellular carcinoma (HCC), the combination therapy of atezolizumab and bevacizumab showed similar overall survival and progression-free survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating its efficacy across age groups.

The safety profile of the combination therapy was comparable between older and younger patients, with similar rates of treatment-related adverse events, including severe adverse events, suggesting that older patients can tolerate this treatment as well as younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Vithayathil, M., D'Alessio, A., Fulgenzi, CAM., et al.[2023]

In a study of 286 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, treatment-related hypertension was linked to better progression-free survival, with a median of 12.6 months compared to 6.5 months for those without hypertension.

Conversely, treatment-related fatigue was associated with shorter overall survival, indicating that while hypertension may signal a positive response to treatment, fatigue could indicate poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Tada, T., Kumada, T., Hiraoka, A., et al.[2023]

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