Combination therapy for hepatocellular carcinoma using atezolizumab, bevacizumab, and memantine

An Open Label Phase II Study of Atezolizumab, Bevacizumab and Memantine in Patients With Hepatocellular Carcinoma

This study is testing a new combination of three medications to see if it can help people with advanced liver cancer feel better and improve their quality of life.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Inova Health Care Services (Academic / other)
• Drugs / interventions: atezolizumab, bevacizumab, Chemotherapy, radiation
• Locations: 2 sites (Fairfax, Virginia and 1 other locations)
• Trial ID: NCT06789757 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of a triplet therapy combining atezolizumab, bevacizumab, and memantine in patients with hepatocellular carcinoma (HCC). The approach focuses on targeting the NMDA receptor pathway while patients undergo systemic therapy. Participants will receive treatment in 21-day cycles over a period of six months, during which their quality of life and cancer-related symptoms will be assessed through surveys. The goal is to evaluate the efficacy and safety of this combination therapy in treating locally advanced and unresectable HCC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with newly diagnosed, untreated hepatocellular carcinoma that is locally advanced and unresectable.

Not a fit: Patients with resectable HCC or those with significant comorbidities that preclude participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option that improves outcomes for patients with hepatocellular carcinoma.

How similar studies have performed: While similar approaches have been explored, this specific combination therapy is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age 18 or older.
2. Patients have newly diagnosed and previously untreated, histologically or radiologically confirmed hepatocellular carcinoma with at least one lesion that is measurable by RECIST 1.1 criteria. A prior HCC lesion that was treated surgically or by radiation is allowed as long as it was at least 2 years or more from the current HCC diagnosis.
3. Patient's cancer must be deemed locally advanced and unresectable
4. Patients must have a Childs-Pugh cirrhosis score of A5 or A6.
5. Eastern Cooperative Oncology Group Performance Status of 0-1.
6. Patients must have bone marrow and organ function as defined below:

   * Absolute Neutrophil Count ≥ 1,500/μL
   * Platelets ≥ 100,000/μL
   * Hemoglobin ≥ 90 g/L (9g/dL)
   * Total Bilirubin ≤ 3 x ULN
   * AST(SGOT)/ALT(SGPT)/Alkaline Phosphatase ≤ 3 x ULN Or ≤5x ULN if due to liver involvement by tumor
   * Creatinine ≤ 2.0 mg/dL
   * eGFR (using Cockcroft Gault equation) \> 40ml/min
7. Chemotherapy is harmful to the human fetus. For this reason, sexually active males and females with partners of childbearing potential must agree to use an accepted and effective method of contraception prior to study entry and for the duration of the study.
8. Patients must demonstrate the ability to understand and the willingness to sign a written informed consent document.
9. Men and women, regardless of race, ethnic group, or sexual orientation are eligible for this study.
10. Patient must be able to swallow oral medication.

Exclusion Criteria:

1. Patients with Childs-Pugh B or C cirrhosis.
2. Female patients who are pregnant or breast-feeding.
3. Concomitant illness that would prevent adequate patient assessment or in the investigators' opinion pose an added risk for study participants.
4. Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator unsuitable for the study. This would include any uncontrolled or untreated viral infection such as HIV, HBV, HCV etc.
5. Subject is enrolled in a separate interventional clinical trial.
6. Active tuberculosis.
7. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
8. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
9. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation.
10. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
11. Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry.
12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment.
13. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

18\. Active, untreated grade 2 or 3 varices. Patients with treated varices to the point that they are grade 1 or less will be allowed.

19\. Patients already on memantine for any reason prior to enrollment will be excluded.

Where this trial is running

Fairfax, Virginia and 1 other locations

• Inova Schar Cancer Institute - Fair Oaks — Fairfax, Virginia, United States (Recruiting)
• Inova Health Care Service — Falls Church, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Arthur Winer, MD — Principal Investigator
• Study coordinator: Keary Jane't

Conditions Hepatocellular Carcinoma; Atezolizumab; Bevacizumab; Memantine