AzTrials
AzTrials

Carcinoma, HepatocellularPhase 3NCT04732286

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

A Phase 3 study testing Atezolizumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 25 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Atezolizumab and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
25 sitesSpain
Study dates
4 May 2021to 26 Apr 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

Spain25 sites

  • Hospital General Univ. de Alicante

    Alicante, 03010

  • Complejo Hospitalario Torrecardenas

    Almería, 04009

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic i Provincial

    Barcelona, 08036

  • Hospital de Basurto

    Bilbao, Vizcaya, 48013

  • Hospital Provincial de Castellon

    Castellon, Castellon, 12002

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital General Universitario de Elche

    Elche, Alicante, 03203

  • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico

    Jaén, 23007

  • Hospital de Gran Canaria Dr. Negrin

    Las Palmas de Gran Canaria, LAS Palmas, 35010

  • Hospital Lucus Augusti

    Lugo, 27003

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Clinica Universidad de Navarra Madrid

    Madrid, 28027

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Son Llatzer

    Palma de Mallorca, Balearic Islands, 07198

  • Clinica Universitaria de Navarra

    Pamplona/iruña, Navarre, 31008

  • Corporacio Sanitaria Parc Tauli

    Sabadell, Barcelona, 08208

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela, LA Coruna, 15706

  • Hospital Univ. Nuestra Señora de Valme

    Seville, 41014

  • Hospital Universitario de Torrejon

    Torrejón de Ardoz, Madrid, 28850

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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.

Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.

  • BevacizumabDrug

    Also called Avastin

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

Study groups in NCT04732286
Study groupRoleWhat they receive
Arm A (atezolizumab plus bevacizumab)ExperimentalParticipants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Receives: Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3

    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.

    Measured: 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 outcomes (9)

  1. Overall Survival (OS)

    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.

    Measured: Up to 35 months

  2. Progression-free Survival (PFS)

    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.

    Measured: Up to 35 months

  3. Objective Response Rate (ORR)

    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.

    Measured: Up to 35 months

  4. Time to Progression (TTP)

    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.

    Measured: Up to 35 months

  5. Duration of Response (DOR)

    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.

    Measured: Up to 35 months

  6. Percentage of Participants Who Started Second-line Treatment

    Participants who started second-line of treatment were assessed. Percentages have been rounded off.

    Measured: Up to 35 months

  7. Change From Baseline in International Normalized Ratio (INR)

    The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.

    Measured: Baseline up to Cycle 42 (1 cycle = 21 days)

  8. Change From Baseline in Albumin-Bilirubin (ALBI) Score

    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.

    Measured: Baseline up to Cycle 42 (1 cycle = 21 days)

  9. Percentage of Participants With Ascites and/or Hepatic Encephalopathy

    Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.

    Measured: Up to approximately 32 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2021
  2. Study start4 May 2021
  3. Primary completion26 Apr 2024
  4. Study completion26 Apr 2024

Why it stopped: The study was completed as pre-specified in the protocol. Study was terminated only for participants who were in the study even after 24 months of follow-up as specified in the protocol.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04732286
Sponsor's protocol ID
ML42600
Status last verified
Apr 2025
First submitted
28 Jan 2021
Last updated
8 May 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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).

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atezolizumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 25 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04732286.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in