LOcoregional vs Systemic Therapy in Patients With BCLC Stage B HCC

NCT05537402 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: STU-2022-0848
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to compare the effectiveness and safety of two standard of care treatments in people who have been diagnosed with hepatocellular carcinoma (HCC).This research study is being done to compare atezolizumab/bevacizumab to locoregional therapy with either transarterial chemoembolization (TACE) or transarterial radioembolization (TARE).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Evaluate the efficacy of atezolizumab and bevacizumab compared to TACE or TARE as measured by progression-free survival after randomization. PFS is defined as time from randomization to death from any cause or radiologic tumor progression, according to investigator assessment per mRECIST (modified Response Evaluation Criteria in Solid Tumors ).

  Baseline until date of first observed disease progression or death, assessed up to 24 months

Secondary Outcomes (5)

• Overall Response Rate

  Baseline until date of first observed disease progression or death, assessed up to 24 months

• Time to treatment Failure

  Baseline until date of first observed disease progression or death, assessed up to 24 months

• Overall Survival

  Baseline until date of death, assessed up to 24 months

• Time to Deterioration of Liver Function

  Randomization until first clinically meaningful deterioration in liver function, assessed up to 24 months

• Time to deterioration of quality of life

  Randomization to first clinically meaningful deterioration of quality of life, assessed up to 24 months

Study Arms (2)

Arm A: Atezolizumab and bevacizumab

EXPERIMENTAL

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle. Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. Atezolizumab will be administered first followed by bevacizumab, with a minimum of 5 minutes between dosing.

Drug: Atezolizumab and bevacizumab

Arm B: Locoregional therapy with TACE or TARE

ACTIVE COMPARATOR

Patients will undergo locoregional therapy with TACE or TARE per investigator preference. TACE will be administered every 8 +/- 4 weeks; TARE will be administered every 12 +/- 4 weeks. Proportion of patients being treated with TARE will be capped at 50% of cohort at a protocol level. After 50% cap is reached, patients randomized to Arm B will be treated with TACE.

Radiation: transarterial chemoembolization (TACE) or transarterial radioembolization (TARE

Interventions

Atezolizumab and bevacizumab DRUG

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle and Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle

Arm A: Atezolizumab and bevacizumab

transarterial chemoembolization (TACE) or transarterial radioembolization (TARE RADIATION

TACE cycles occur every 8 weeks +/- 7 days OR TARE cycles occur every 12 weeks +/- 7 days

Arm B: Locoregional therapy with TACE or TARE

Eligibility Criteria

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

You may qualify if:

• Patients with confirmed HCC by imaging (LI-RADS 5) or histopathology
• Treatment-naïve, liver localized (intermediate-stage), i.e., beyond Milan Criteria (one tumor ≤5 cm, or two to three tumors, each ≤3 cm) and not amenable to curative surgery, liver transplantation, or local ablation and no evidence of extrahepatic disease or vascular invasion.
• Child Pugh class A
• Age ≥18 years at time of screening
• ECOG Performance Status 0 or 1
• Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV NA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
• Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/ml or under the limit of detection per local lab standard) are not required to start antiviral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
• Patients with HCV infection, defined by presence of detectable antibody or RNA, should have management of this disease per local institutional practice throughout the study.
• At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria: • Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase
• Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter
• Adequate organ and marrow function at enrollment as defined below:
• Hemoglobin ≥9.0 g/dL Patients may be transfused to meet this criterion.
• Absolute neutrophil count ≥1500/μL
• Platelet count ≥75000/μL
• Total bilirubin ≤3 × the upper limit of normal (ULN)

You may not qualify if:

• Chemotherapy, radiotherapy, or other cancer therapy within 3 months prior to starting study treatment.
• Any prior immunotherapy for malignancy.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Patients with infiltrative-type HCC
• Definite macrovascular invasion or distant metastatic disease at randomization
• Clinically significant ascites, requiring non-pharmacological intervention (e.g., paracentesis) to maintain control within past 6 months
• History of hepatic encephalopathy within past 6 months
• Actively listed or under evaluation for liver transplantation
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Active tuberculosis

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Hsieh, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Internal Medicine

Model Details: Patients will be randomly assigned to one of two study arms: Arm A: Atezolizumab and bevacizumab or Arm B: Locoregional therapy with TACE or TARE as determined by local site. Randomization will occur on 1:1 ratio through permuted-block randomization method and will be stratified.

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 13, 2022
• Study Start: September 27, 2023
• Primary Completion: June 6, 2025
• Study Completion: June 6, 2025
• Last Updated: September 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)