Clinical trial NCT06806579: Atezolizumab-bevacizumab and Other Immunotherapies: Real-life Experience for Treatment of Hepatocellular Carcinoma
Official title: Atezolizumab-bevacizumab and Other Immunotherapies: Real-life Experience for Treatment of Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: atezolizumab
bevacizumab
tremelimumab
durvalumab
immunotherapy
real-life
outcome
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2025-02-04
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: - 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate toxicity as first-line therapy
timeFrame: from enrollment up to 3 years from the first dose
Secondary outcomes:
measure: Progression-free survival
timeFrame: from enrollment up to 3 years from the first dose
measure: Overall survival
timeFrame: from enrollment up to 3 years from the first dose
measure: Objective response rate (ORR)
timeFrame: from enrollment up to 3 years from the first dose
measure: Rate of Patients Eligible for Second-Line Treatments
timeFrame: from enrollment up to 3 years from the first dose
measure: Safety monitoring
timeFrame: from enrollment up to 3 years from the first dose
Other outcomes:
Locations:
city: Torrette
country: Italy
facility: Ospedali Riuniti Ancona, Via Conca, 71, 60126 Torrette AN
state: AN
city: Castellana Grotte
country: Italy
facility: I.R.C.C.S. "S. De Bellis", Via Turi, 27, 70013 Castellana Grotte BA
state: BA
city: Bologna
country: Italy
facility: AUSL Bologna Via Castiglione 15 40136 Bologna BO
state: BO
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna (Oncology Unit), Bologna, BO 40136
state: BO
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna (Semiotics Unit)
state: BO
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
state: BO
city: Catania
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione "Garibaldi, Piazza Santa Maria di Gesù, 5, 95123 Catania CT
state: CT
city: Foggia
country: Italy
facility: Ospedali Riuniti. Viale Pinto Luigi, 1, 71122 Foggia FG.
state: FG
city: Foggia
country: Italy
facility: Ospedali Riuniti. Viale Pinto Luigi, 1, 71122 Foggia FG
state: FG
city: Firenze
country: Italy
facility: AOU Careggi. Largo G. Alessandro Brambilla, 3. 50134 Firenze FI
state: FI
city: Modena
country: Italy
facility: Policlinico di Modena Via del Pozzo, 71, 41125 Modena MO
state: Missouri
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. via Francesco Sforza, 28 - 20122 Milano.
state: MI
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162 Milano
state: MI
city: Rozzano
country: Italy
facility: Humanitas Research Hospital. Via Alessandro Manzoni, 56, 20089 Rozzano MI
state: MI
city: Palermo
country: Italy
facility: Azienda Ospedaliero- Universitaria Paolo Giaccone. Via Liborio Giuffrè, 5, 90127 Palermo
state: PA
city: Padova
country: Italy
facility: Istituto Oncologico Veneto. Via Gattamelata, 64, 35128 Padova PD
state: PD
city: Pisa
country: Italy
facility: AOU Pisana. Via Roma 67. 56126 Pisa PI
state: PI
city: Faenza
country: Italy
facility: Ospedale degli Infermi Viale Stradone, 9 48018 Faenza (RA)
state: RA
city: Reggio Emilia
country: Italy
facility: IRCCS Santa Maria Nuova Viale Risorgimento, 80, 42123 Reggio Emilia
state: RE
city: Roma
country: Italy
facility: Policlinico Gemelli. Largo Agostino Gemelli, 8, 00168 Roma RM
state: RM
city: Udine
country: Italy
facility: Azienda sanitaria universitaria Friuli Centrale, Piazzale Santa Maria della Misericordia, 15 33100 Udine (UD)
state: UD
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona. Piazzale Aristide Stefani, 1, 37126 Verona VR
state: VR
city: Napoli
country: Italy
facility: P.O. Ospedale del Mare. Via Enrico Russo, 11, 80147 Napoli NA
city: Novara
country: Italy
facility: Azienda Ospedaliero- Universitaria Maggiore della Carità, Padiglione G, L.go Bellini, 28100 Novara NO
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Francesco Tovoli, MD
role: PRINCIPAL_INVESTIGATOR
References: