The Study of Atezolizumab, Bevacizumab and Memantine in Patients With Hepatocellular Carcinoma (HCC)

NCT06789757 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: INOVA-2023-74
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research is to see the effect of triplet therapy with atezolizumab, bevacizumab, and memantine in treatment of your hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

Atezolizumab; Bevacizumab; Memantine

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) of patients who are treated with the combination of atezolizumab, bevacizumab, and memantine.

  The effectiveness of the combination therapy using Azozolizumab, Bevacizumab,and Memantine in relation to the Objective Response Rate (ORR), defined as the proportion of complete or partial responses to the treatment by the response evaluation criteria for solid tumors(RECIST) 1.1.

  Up to 2 years

Study Arms (1)

Addition of Memantine to Atezolizumab and Bevacizumab (the current systemic standard of care)

EXPERIMENTAL

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

Drug: Memantine Hydrochloride; Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Memantine Hydrochloride DRUG

Memantine (5mg) is an N-methyl-D-aspartate (NMDA) receptor antagonist given in 21-day cycles over six months in combination with Bevacizumab and Atezolizumab. Each week memantine will be escalated by 5mg as tolerated

Also known as: Namenda

Addition of Memantine to Atezolizumab and Bevacizumab (the current systemic standard of care)

Bevacizumab DRUG

Bevacizumab (15mg/kg) is a vascular endothelial growth factor inhibitor given in 21-day cycles over six months in combination with Memantine and Atezolizumab.

Also known as: Avastin

Addition of Memantine to Atezolizumab and Bevacizumab (the current systemic standard of care)

Atezolizumab DRUG

Atezolizumab (1200mg) is a programmed death-ligand 1 (PD-L1) blocking antibody given in 21-day cycles over six months in combination with Memantine and Bevacizumab

Also known as: Tecentriq

Addition of Memantine to Atezolizumab and Bevacizumab (the current systemic standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older.
• 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.
• Patient's cancer must be deemed locally advanced and unresectable
• Patients must have a Childs-Pugh cirrhosis score of A5 or A6.
• Eastern Cooperative Oncology Group Performance Status of 0-1.
• 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
• 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.
• Patients must demonstrate the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients with Childs-Pugh B or C cirrhosis.
• Female patients who are pregnant or breast-feeding.
• Concomitant illness that would prevent adequate patient assessment or in the investigators' opinion pose an added risk for study participants.
• 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.
• Subject is enrolled in a separate interventional clinical trial.
• Active tuberculosis.
• 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.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or bevacizumab formulation.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment.
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• \. Active, untreated grade 2 or 3 varices. Patients with treated varices to the point that they are grade 1 or less will be allowed.
• \. Patients already on memantine for any reason prior to enrollment will be excluded.

Sponsors & Collaborators

• Inova Health Care Services: lead

Study Sites (2)

Inova Schar Cancer Institute - Fair Oaks

Fairfax, Virginia, 22033, United States

RECRUITING

Inova Health Care Service

Falls Church, Virginia, 22042, United States

RECRUITING

Related Publications (7)

• Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther. 2010 Feb 15;31(4):461-76. doi: 10.1111/j.1365-2036.2009.04200.x. Epub 2009 Nov 19.

  PMID: 19925500 BACKGROUND

• Rawla P, Sunkara T, Muralidharan P, Raj JP. Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn). 2018;22(3):141-150. doi: 10.5114/wo.2018.78941. Epub 2018 Sep 30.

  PMID: 30455585 BACKGROUND

• El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology. 2014 Nov;60(5):1767-75. doi: 10.1002/hep.27222. Epub 2014 Aug 25. No abstract available.

  PMID: 24839253 BACKGROUND

• Liu P, Xie SH, Hu S, Cheng X, Gao T, Zhang C, Song Z. Age-specific sex difference in the incidence of hepatocellular carcinoma in the United States. Oncotarget. 2017 Jul 12;8(40):68131-68137. doi: 10.18632/oncotarget.19245. eCollection 2017 Sep 15.

  PMID: 28978103 BACKGROUND

• Kim E, Viatour P. Hepatocellular carcinoma: old friends and new tricks. Exp Mol Med. 2020 Dec;52(12):1898-1907. doi: 10.1038/s12276-020-00527-1. Epub 2020 Dec 2.

  PMID: 33268834 BACKGROUND

• Amit S, Jorge A M. Screening for hepatocellular carcinoma. Gastroenterol Hepatol (N Y). 2008 Mar;4(3):201-8.

  PMID: 21904498 BACKGROUND

• Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J Hepatol. 2020 Feb;72(2):250-261. doi: 10.1016/j.jhep.2019.08.025.

  PMID: 31954490 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Memantine; Bevacizumab; atezolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Arthur Winer, MD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keary Jane't

CONTACT

571-472-4724; keary.janet@inova.org

Elahe Mollapour

CONTACT

571-472-4724; elahe.mollapour@inova.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2024
• First Posted: January 23, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): October 27, 2026
• Study Completion (Estimated): January 27, 2028
• Last Updated: October 7, 2025

Record last verified: 2025-10

Locations

US (2)