Atezolizumab-bevacizumab and Other Immunotherapies: Real-life Experience for Treatment of Hepatocellular Carcinoma (ARTE)

January 28, 2025 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

- Background Hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third leading cause of cancer-related death. In most cases (about 80%), HCC develops in a cirrhotic liver - a condition where the liver has been damaged over time, leading to scarring. This makes treatment more challenging.

This study will gather and analyze data from patients treated in real-world settings to:

  1. Understand the effectiveness and safety of new treatment combinations (e.g., atezolizumab-bevacizumab and durvalumab-tremelimumab).

    Identify the best treatment sequences for patients with advanced liver cancer.

  2. Discover clinical and laboratory markers that predict treatment responses, helping personalize care and optimize outcomes.

By addressing these questions, this study will provide valuable information to healthcare providers and guide future treatment decisions for patients with liver cancer.

Study Overview

Status

Recruiting

Conditions

Detailed Description

  • Background Hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third leading cause of cancer-related death. In most cases (about 80%), HCC develops in a cirrhotic liver - a condition where the liver has been damaged over time, leading to scarring. This makes treatment more challenging.
  • New Advances in Treatment Options

For many years, sorafenib was the only approved drug for advanced liver cancer when local treatments like surgery were not possible. However, significant advancements have changed the treatment landscape:

  1. Atezolizumab and Bevacizumab (Immunotherapy Combination):

    In 2019, a groundbreaking study (ImBRAVE-150, Phase 3) demonstrated that combining atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenic drug) significantly improved disease-free survival (time without cancer worsening) and overall survival compared to sorafenib.

    This combination was approved in 2019 by the European Medicines Agency (EMA) and later by the Italian Medicines Agency (AIFA) in 2022.

  2. Durvalumab and Tremelimumab (Dual Immunotherapy):

In February 2024, another combination-durvalumab and tremelimumab-was introduced following the results of the Phase 3 HIMALAYA trial, which also showed improved outcomes compared to sorafenib.

Several other immunotherapy-based combinations, such as camrelizumab-rivoceranib and nivolumab-ipilimumab, are under evaluation and may become available in the future.

  • Why Is This Study Important?

    1. Real-World Effectiveness of Treatments:

      While clinical trials have shown promising results for atezolizumab-bevacizumab and durvalumab-tremelimumab, real-world data-information gathered from everyday clinical practice-are still limited. In particular, there is a lack of real-world evidence for the new durvalumab-tremelimumab combination. This study aims to fill that gap by collecting and analyzing data from patients treated in daily clinical practice.

    2. Understanding Treatment Sequences:

      After completing atezolizumab-bevacizumab or durvalumab-tremelimumab, what is the best next treatment? Currently, the only approved next-line drug is sorafenib, and for third-line treatment in Italy, cabozantinib is the only option. However, there is no clear scientific data on the effectiveness of these treatment sequences.

      As more therapies become available, it will be critical to identify the best sequence of treatments to extend survival and improve quality of life.

    3. Identifying Predictors of Response:

      Some patients respond better to treatment than others. This study seeks to identify clinical and laboratory markers that predict which patients will benefit most from specific therapies.

      For example, with sorafenib, the development of certain side effects (like skin reactions) was associated with better survival. It remains unclear whether similar markers exist for newer drug combinations.

      Additionally, the study will examine how factors such as treatment intolerance, patterns of disease progression, and second-line therapies influence survival outcomes.

  • What This Study Aims to Achieve

This study will gather and analyze data from patients treated in real-world settings to:

  1. Understand the effectiveness and safety of new treatment combinations (e.g., atezolizumab-bevacizumab and durvalumab-tremelimumab).

    Identify the best treatment sequences for patients with advanced liver cancer.

  2. Discover clinical and laboratory markers that predict treatment responses, helping personalize care and optimize outcomes.

By addressing these questions, this study will provide valuable information to healthcare providers and guide future treatment decisions for patients with liver cancer.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Napoli, Italy, 80147
        • Recruiting
        • P.O. Ospedale del Mare. Via Enrico Russo, 11, 80147 Napoli NA
        • Contact:
      • Novara, Italy, 28100
        • Not yet recruiting
        • Azienda Ospedaliero- Universitaria Maggiore della Carità, Padiglione G, L.go Bellini, 28100 Novara NO
        • Contact:
    • AN
      • Torrette, AN, Italy, 60126
        • Recruiting
        • Ospedali Riuniti Ancona, Via Conca, 71, 60126 Torrette AN
        • Contact:
    • BA
      • Castellana Grotte, BA, Italy, 70013
        • Not yet recruiting
        • I.R.C.C.S. "S. De Bellis", Via Turi, 27, 70013 Castellana Grotte BA
        • Contact:
    • BO
      • Bologna, BO, Italy, 40136
      • Bologna, BO, Italy, 40136
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna (Oncology Unit), Bologna, BO 40136
        • Contact:
      • Bologna, BO, Italy, 40136
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna (Semiotics Unit)
        • Contact:
      • Bologna, BO, Italy, 40136
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:
    • CT
      • Catania, CT, Italy, 95123
        • Not yet recruiting
        • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione "Garibaldi, Piazza Santa Maria di Gesù, 5, 95123 Catania CT
        • Contact:
    • FG
      • Foggia, FG, Italy, 71122
        • Recruiting
        • Ospedali Riuniti. Viale Pinto Luigi, 1, 71122 Foggia FG.
        • Contact:
      • Foggia, FG, Italy, 71122
        • Not yet recruiting
        • Ospedali Riuniti. Viale Pinto Luigi, 1, 71122 Foggia FG
        • Contact:
    • FI
      • Firenze, FI, Italy, 50134
        • Recruiting
        • AOU Careggi. Largo G. Alessandro Brambilla, 3. 50134 Firenze FI
        • Contact:
    • MI
      • Milano, MI, Italy, 20122
        • Recruiting
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. via Francesco Sforza, 28 - 20122 Milano.
        • Contact:
      • Milano, MI, Italy, 20162
        • Not yet recruiting
        • ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162 Milano
        • Contact:
      • Rozzano, MI, Italy, 20089
    • Missouri
      • Modena, Missouri, Italy, 41125
        • Not yet recruiting
        • Policlinico di Modena Via del Pozzo, 71, 41125 Modena MO
        • Contact:
    • PA
      • Palermo, PA, Italy, 90127
        • Recruiting
        • Azienda Ospedaliero- Universitaria Paolo Giaccone. Via Liborio Giuffrè, 5, 90127 Palermo
        • Contact:
    • PD
      • Padova, PD, Italy, 35128
        • Recruiting
        • Istituto Oncologico Veneto. Via Gattamelata, 64, 35128 Padova PD
        • Contact:
    • PI
      • Pisa, PI, Italy, 56126
        • Recruiting
        • AOU Pisana. Via Roma 67. 56126 Pisa PI
        • Contact:
    • RA
      • Faenza, RA, Italy, 48018
        • Recruiting
        • Ospedale degli Infermi Viale Stradone, 9 48018 Faenza (RA)
        • Contact:
    • RE
      • Reggio Emilia, RE, Italy, 42123
        • Not yet recruiting
        • IRCCS Santa Maria Nuova Viale Risorgimento, 80, 42123 Reggio Emilia
        • Contact:
    • RM
      • Roma, RM, Italy, 00168
        • Recruiting
        • Policlinico Gemelli. Largo Agostino Gemelli, 8, 00168 Roma RM
        • Contact:
    • UD
      • Udine, UD, Italy, 33100
        • Not yet recruiting
        • Azienda sanitaria universitaria Friuli Centrale, Piazzale Santa Maria della Misericordia, 15 33100 Udine (UD)
        • Contact:
    • VR
      • Verona, VR, Italy, 37126
        • Recruiting
        • Azienda Ospedaliera Universitaria Integrata di Verona. Piazzale Aristide Stefani, 1, 37126 Verona VR
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Data will be collected from patients with hepatocellular carcinoma (HCC) who are candidates for treatment with atezolizumab-bevacizumab or durvalumab-tremelimumab. Patients will be evaluated in outpatient clinics or inpatient departments of the participating centers as part of the standard care pathway for HCC patients. Data will be collected at the patient's first evaluation and during subsequent assessments (approximately every 3-4 weeks), as per the routine care process for HCC patients receiving pharmacological treatments. The follow-up observation for each patient will continue as part of the standard care pathway.

Description

Inclusion Criteria:

  • Hepatocellular carcinoma not amenable to locoregional procedures
  • Candidate to frontline systemic treatment with atezolizumab-bevacizumab or other immunotherapies

Exclusion Criteria:

  • Concurrent treatment with other antineoplastic agents
  • Other active neoplasia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate toxicity as first-line therapy
Time Frame: from enrollment up to 3 years from the first dose

To evaluate toxicity of therapeutic sequences in which atezolizumab-bevacizumab or other immunothrapies were administered as first-line therapy within the standard care pathway for patients with hepatocellular carcinoma.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
from enrollment up to 3 years from the first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: from enrollment up to 3 years from the first dose
defined as the time between the first administration of atezolizumab-bevacizumab or durvalumab-tremelimumab and radiological progression
from enrollment up to 3 years from the first dose
Overall survival
Time Frame: from enrollment up to 3 years from the first dose
defined as the time between the treatment start and the death of the patient, or to the last follow-up evaluation
from enrollment up to 3 years from the first dose
Objective response rate (ORR)
Time Frame: from enrollment up to 3 years from the first dose
defined as the percentage of patients who achieve a partial or complete response to the disease on follow-up imaging, according to RECIST 1.1 criteria, out of the total number of patients who undergo at least one radiological assessment.
from enrollment up to 3 years from the first dose
Rate of Patients Eligible for Second-Line Treatments
Time Frame: from enrollment up to 3 years from the first dose
defined as the percentage of patients who, after the definitive discontinuation of atezolizumab-bevacizumab or other immunotherapies, have sufficiently good general conditions and liver function to allow the prescription of an additional line of systemic treatment.
from enrollment up to 3 years from the first dose
Safety monitoring
Time Frame: from enrollment up to 3 years from the first dose
Incidence of Adverse Events Related to Atezolizumab-Bevacizumab or other immunotherapies
from enrollment up to 3 years from the first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

  • Principal Investigator: Francesco Tovoli, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2022

Primary Completion (Estimated)

October 31, 2030

Study Completion (Estimated)

October 31, 2031

Study Registration Dates

First Submitted

January 10, 2025

First Submitted That Met QC Criteria

January 28, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 28, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARTE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Privacy regulations

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma (HCC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe