A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

April 22, 2025 updated by: Hoffmann-La Roche

A Phase IIIb, Single Arm, Multicenter Study of Atezolizumab in Combination With Bevacizumab to Investigate Safety and Efficacy in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Locations

  • Spain
      • Alicante, Spain, 03010
        • Hospital General Univ. de Alicante
      • Almeria, Spain, 04009
        • Complejo Hospitalario Torrecárdenas
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08036
        • Hospital Clínic i Provincial
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Jaen, Spain, 23007
        • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
      • Lugo, Spain, 27003
        • Hospital Lucus Augusti
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28040
        • Hospital Clínico San Carlos
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra Madrid
      • Sevilla, Spain, 41014
        • Hospital Univ. Nuestra Señora de Valme
      • Valencia, Spain, 46026
        • Hospital Universitari i Politècnic La Fe
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
    • Castellon
      • Castellon de La Plana, Castellon, Spain, 12002
        • Hospital Provincial de Castellon
    • Islas Baleares
      • Palma de Mallorca, Islas Baleares, Spain, 07198
        • Hospital Son Llàtzer
    • LA Coruna
      • Santiago de Compostela, LA Coruna, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS)
    • LAS Palmas
      • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35010
        • Hospital de Gran Canaria Dr. Negrín
    • Madrid
      • Torrejón de Ardoz, Madrid, Spain, 28850
        • Hospital Universitario de Torrejon
    • Navarra
      • Pamplona/iruña, Navarra, Spain, 31008
        • Clinica Universitaria De Navarra
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or radiologically, following the AASLD criteria
  • Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
  • No prior systemic therapy (including systemic investigational agents) for HCC
  • At least one measurable (per RECIST 1.1) untreated lesion detected by CT scan
  • Patients who received prior local therapy such as radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization (excluding transarterial radioembolization.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1

Exclusion Criteria:

  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • Co-infection of HBV and HCV

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A (atezolizumab plus bevacizumab)
Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Drug: Atezolizumab
Atezolizumab will be administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq
Drug: Bevacizumab
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3
Time Frame: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)
AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of AEs was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) with the following grades: Grade 1 = asymptomatic or mild symptoms; Grade 2 = minimal, local, or non-invasive intervention indicated; Grade 3 = severe or medically significant, but not immediately life-threatening; Grade 4 = life-threatening consequences or urgent intervention indicated and Grade 5 = death related to AE.
From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 35 months
OS was defined as the time from initiation of study treatment to death from any cause. OS was analyzed using Kaplan-Meier (K-M) methods and Greenwood's formula. Any participant who did not die during the study was censored at the last known date to be alive.
Up to 35 months
Progression-free Survival (PFS)
Time Frame: Up to 35 months
PFS was defined as the time from initiation of study treatment to the first occurrence of disease progression (PD) or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm). PFS was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study and were censored at the last known date to be alive or without disease progression.
Up to 35 months
Objective Response Rate (ORR)
Time Frame: Up to 35 months
ORR = percentage of participants with a complete or partial response (CR or PR), on 2 consecutive investigator assessments ≥ 4 weeks apart in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to < 10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants without a post-baseline tumor assessment were considered non-responders. 95% confidence interval (CI) was derived using Wilson score intervals. Percentages have been rounded off.
Up to 35 months
Time to Progression (TTP)
Time Frame: Up to 35 months
TTP was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, SOD must also demonstrate an absolute increase of ≥ 5 mm. TTP was analyzed using K-M methods and Greenwood's formula. Any participant who had no disease progression was censored at the last known date without disease progression.
Up to 35 months
Duration of Response (DOR)
Time Frame: Up to 35 months
DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study was censored at the last known date to be alive or without disease progression.
Up to 35 months
Percentage of Participants Who Started Second-line Treatment
Time Frame: Up to 35 months
Participants who started second-line of treatment were assessed. Percentages have been rounded off.
Up to 35 months
Change From Baseline in International Normalized Ratio (INR)
Time Frame: Baseline up to Cycle 42 (1 cycle = 21 days)
The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.
Baseline up to Cycle 42 (1 cycle = 21 days)
Change From Baseline in Albumin-Bilirubin (ALBI) Score
Time Frame: Baseline up to Cycle 42 (1 cycle = 21 days)
Blood samples were collected from participants to evaluate of ALBI grades. ALBI assessment grades of 1 to 3 was based on ALBI score calculation. ALBI score= log10 bilirubin (micromole per liter) [μmol/L] × 0.66 + albumin (grams per liter) [g/L] × -0.0852. ALBI score ≤ -2.60 = ALBI grade 1; -2.60 < ALBI score ≤ -1.39 = ALBI grade 2 and -1.39 < ALBI score = ALBI grade 3.
Baseline up to Cycle 42 (1 cycle = 21 days)
Percentage of Participants With Ascites and/or Hepatic Encephalopathy
Time Frame: Up to approximately 32 months
Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.
Up to approximately 32 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 4, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 26, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 26, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML42600

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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 Carcinoma, Hepatocellular

Clinical Trials on Atezolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings