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Hepatocellular CarcinomaPhase 2AB-LATE02NCT04727307

Neoadjuvant Atezo, Adjuvant Atezo + Beva Combined With RF Ablation of Small HCC: a Multicenter Randomized Phase II Trial

A Phase 2 study testing Atezolizumab (neoadjuvant), Percutaneous Radiofrequency and Bevacizumab (adjuvant) in people with Hepatocellular Carcinoma, run by University Hospital, Montpellier at 19 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Following the results of study IMbrave150, the combination Atezolizumab + Bevacizumab is a promising treatment option for patients with HCC. In addition, the high intrahepatic distant recurrence rate and accumulating evidence for a metastatic mechanism encourages exploring adjuvant/neoadjuvant strategies targeting… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Atezolizumab (neoadjuvant), Percutaneous Radiofrequency and Bevacizumab (adjuvant)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
19 sitesFrance
Study dates
23 Feb 2021to Feb 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Male or female patients ≥ 18 years of age
  • Diagnostic of HCC based on Imaging (EASL guidelines)
  • Patients with HCC eligible for ablation as assessed by multidisciplinary board:
  • All HCC nodules <3cm
  • 1-3 nodules of HCC
  • At least one uni-dimensional measurable lesion by magnetic resonance imaging (MRI) according to modified RECIST criteria
Show all 21Show fewer
  • Liver function status Child-Pugh Class A
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
  • Hemoglobin > 8.5 g/dL
  • Absolute neutrophil count ≥ 1500/mm3
  • Platelet count ≥ 50,000/ mm3
  • Total bilirubin ≤ 2 mg/dL (ou ≤ 34 µmol/ L).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 x ULN
  • Lipase ≤ 2 x ULN
  • Prothrombin time > 50%
  • Glomerular Filtration Rate (GFR) ≥ 35 mL/min/1.73 m2
  • Life expectancy ≥ 3 months
  • Women of childbearing potential and men must agree to use adequate contraception
  • Patients affiliated to a Social Security System

Who cannot join

  • Patients with contraindications to ablation or atezolizumab or bevacizumab
  • Patients with contraindication to contrast medium intravenous injection either gadolinium or iodinate
  • Patients with contraindication to MRI
  • Prior liver transplantation
  • Child-Pugh B or C
  • Patients with mixed histology (HCC and cholangiocarcinoma, namely hepatocholangiocarcinoma), if a biopsy is available
Show all 40Show fewer
  • Current or recent (≤ 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR < 1.5 x ULN and aPTT is within normal limits within 14 days prior to initiation of study treatment. For prophylactic use of anticoagulants or thrombolytic therapies, the approved dose as described by local label may be used.
  • Current or recent (≤10 days prior to initiation of study treatment) use of aspirin (> 325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol.
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
  • Rash must cover < 10% of body surface area.
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids.
  • Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need forsystemic immunosuppressive medication during study treatment, with the following exceptions:
  • Patients who received acute, low-dose systemic immunosuppressant medication or a onetime pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor confirmation has been obtained.
  • Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  • Portal vein invasion, whatever its extent, shown on baseline imaging
  • Prior chemo-embolization or radio-embolization.
  • Patients with extra-hepatic metastases, either previously-treated or not. One lung nodule (<5mm) is allowed. Calcified lung micronodules as well as typical intra-pulmonary lymph nodes are allowed. Hepatic hilum lymph node < 10mm (short axis) is allowed.
  • Prior surgery of HCC with micro- or macro-vascular invasion demonstrated at pathology.
  • Prior systemic treatment for HCC, in particular agents targeting T-cell costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or PD-L2, cluster of differentiation 137 (CD137), or cytotoxic T-lymphocyte antigen (CTLA-4)).
  • Patients with uncontrolled HBV infection and viral load above 500 IU/mL.
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure
  • Past or concurrent history of neoplasm other than HCC, except for in-situ carcinoma of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors. Any cancer curatively treated > 3 years prior to study entry is permitted
  • Known history or symptomatic meningeal tumors
  • Grade 3 (severe) hypertension ≥160 and/or ≥100 mmHG (systolic and diastolic, according to NCI-CTCAE v5.0)
  • Patients with phaeochromocytoma
  • Ongoing infection : Hepatitis B is allowed if no active replication is present (HBV replication below 500 IU/mL) or Hepatitis C is allowed if no antiviral treatment is required
  • Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days before enrolment (transfusion indicated)
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 6 months before enrolment
  • Any psychological, familial, sociological, geographical or illness or medical condition that could jeopardize the safety of the patient and/or his compliance with the study protocol and follow-up procedure
  • Known history of human immunodeficiency virus (HIV) infection
  • Seizure disorder requiring medication
  • Non-healing wound, ulcer or bone fracture
  • Breast feeding
  • Pregnancy
  • Legal incapacity (persons in custody or under guardianship)
  • Deprived of liberty Subject (by judicial or administrative decision)

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

France19 sites

  • CHU Amiens

    Amiens

  • CHU d'Angers

    Angers

  • Hôpital Jean Verdier

    Bondy

  • Hôpital Beaujon

    Clichy

  • Centre Georges François Leclerc

    Dijon

  • CHU Dijon

    Dijon

  • CHU de Grenoble

    Grenoble

  • CHU de Lille

    Lille

  • Hôpital Saint Joseph

    Marseille

  • CHU de Montpellier

    Montpellier

  • CHRU de Nancy

    Nancy

  • CHU de Nantes

    Nantes

  • CHU de Nice

    Nice

  • CHU Nîmes

    Nîmes

  • Hôpital Cochin

    Paris

  • CH Perpignan

    Perpignan

  • CHU de Poitiers

    Poitiers

  • CHU de Rennes

    Rennes

  • Institut Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: Neoadjuvant Atezolizumab and Adjuvant Atezolizumab + Bevacizumab in Combination With Percutaneous Radiofrequency Ablation of Small HCC: a Multicenter Randomized Phase II Trial

Following the results of study IMbrave150, the combination Atezolizumab + Bevacizumab is a promising treatment option for patients with HCC.

In addition, the high intrahepatic distant recurrence rate and accumulating evidence for a metastatic mechanism encourages exploring adjuvant/neoadjuvant strategies targeting tumor growth and metastatic escape in the context of percutaneous thermal ablation for small HCC.

Local ablation of HCC is therefore an "ideal" setting for testing atezolizumab + bevacizumab in combination with ablation, with the aim of reducing the risk of recurrence.

Read the detailed description

Liver cancer is the sixth most common cancer and the third leading cause of death from cancer worldwide (source: Globocan 2018). Hepatocellular carcinoma (HCC) represents 80-90% of liver cancers. Percutaneous thermal ablation (PTA) is a validated treatment option for very early and early stage HCC, together with surgical resection and liver transplantation (EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma, J Hepatol 2018). Due to its excellent tolerance, particularly in patients with portal hypertension or bearing comorbidities, it now represents in France nearly 70% of the first-line curative treatment of "in Milan" tumours. The risk of local tumor progression (LTP) is ≈10-20% in PTA series (Nault, J Hepatol 2018; N'Kontchou et al., Hepatology (Baltimore, Md) 2009). In addition, the long-term results of PTA are influenced by the high rate (up to 60-80% at 5 years) of intrahepatic distant recurrence (IDR) (Nault et al., J Hepatol 2018), as observed also after HCC surgical resection (EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma, J Hepatol 2018; Imamura et al., J Hepatol 2003). It is unknown whether early IDR (2-3 years after PTA of <3 cm HCC) is due to metastatic spread or de novo carcinogenesis.

Strong scientific rationale and emerging clinical data suggest that the combined vascular endothelial growth factor (VEGF) / Programmed death-ligand 1 (PD-L1) blockade may be clinically beneficial in a number of tumor types, including HCC. Therefore, local ablation in HCC is an " ideal " context to test Atezolizumab + Bevacizumab in combination with ablation. The investigators hypothesized that the combo of Atezolizumab + Bevacizumab and radiofrequency ablation could improve recurrence-free survival (RFS) at 2 years.

The aim of this randomized multicentre phase II trial is to compare RFS at 2 years in the experimental arm (Atezolizumab + Bevacizumab + RF ablation) versus the control arm (RF ablation) according to HCC modified response evaluation criteria in solid tumours (mRECIST). Thus the proposed use here of Atezolizumab as first neoadjuvant, then in combination with Bevacizumab as adjuvants, should theoretically, and hopefully, limit the radiofrequency ablation (RFA) pro-tumor effects. The RFS current rate value of 45% corresponding to the standard procedure of RFA alone (i.e. in the Active Comparator arm) should be increasing to at least 65% because of the addition of the biotherapy (i.e. in the Experimental arm). The patients' recruitment timeframe is set at 36 months and the patient's follow-up timeframe is 5 years. 202 patients are to be included, 101 per arm.

Being tested
Atezolizumab (neoadjuvant), Percutaneous Radiofrequency, Bevacizumab (adjuvant), Atezolizumab (adjuvant)
Keywords
Atezolizumab, Bevacizumab, Percutaneous radiofrequency, Ablation, Liver disease
Medical subject headings
Carcinoma, Hepatocellular, Liver Diseases

What participants receive

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

  • Atezolizumab (neoadjuvant)Drug

    Also called Tecentriq

    Atezolizumab 1200mg will be delivered as an IV infusion on Day 1 of each cycle (every 3 weeks) in neoadjuvant, for 2 cycles. The initial dose will be delivered over 60 (± 15) minutes and if tolerated subsequent infusions may be given over 30 (± 10) minutes.

  • Percutaneous RadiofrequencyProcedure or surgery

    Any RFA system (uni/multi-needle, monopolar or multi-bi-polar) is allowed. Microwave ablation or irreversible electroporation is not allowed.

  • Bevacizumab (adjuvant)Drug

    Also called Avastin 400 mg in 16 ml Injection, Avastin 100 mg in 4 ml Injection

    Bevacizumab 15 mg/kg will be delivered as an IV infusion on Day 1 of each 3 week cycle in adjuvant, for 15 cycles maximum. The initial dose will be delivered over 90 minutes (±15 minutes) and if tolerated subsequent infusions may be given over 60 (± 10) minutes then over 30 (± 10) minutes.

  • Atezolizumab (adjuvant)Drug

    Also called Tecentriq

    Atezolizumab 1200 mg will be delivered as an IV infusion on Day 1 of each cycle (every 3 weeks) in adjuvant, for 15 cycles maximum. The dose will be delivered over 30 (± 10) minutes.

Study groups in NCT04727307
Study groupRoleWhat they receive
Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + BevacizumabExperimentalNeoadjuvant atezolizumab and adjuvant atezolizumab + bevacizumab in combination with percutaneous radiofrequency ablation
Receives: Drug: Atezolizumab (neoadjuvant); Procedure: Percutaneous Radiofrequency; Drug: Bevacizumab (adjuvant); Drug: Atezolizumab (adjuvant)
Percutaneous radiofrequency ablationActive comparatorPercutaneous radiofrequency ablation, standard treatment
Receives: Procedure: Percutaneous Radiofrequency

What is being measured

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

  1. Recurrence-free survival

    The primary outcome is to compare recurrence-free survival in patients treated by radiofrequency ablation versus neoadjuvant atezolizumab followed by radiofrequency ablation followed by adjuvant atezolizumab and bevacizumab.Recurrence is evaluated by the local investigator.

    Measured: 2 years after randomization

Timeline

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

  1. First posted27 Jan 2021
  2. Study start23 Feb 2021
  3. Primary completionFeb 2028 (estimated)
  4. Study completionFeb 2031 (estimated)

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
202 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04727307
Sponsor's protocol ID
RECHMPL20_0094
Other IDs
2024-519113-59-00, 2020-000569-18
Acronym
AB-LATE02
Status last verified
Jun 2026
First submitted
22 Jan 2021
Last updated
22 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab (neoadjuvant), Percutaneous Radiofrequency and Bevacizumab (adjuvant) in people with Hepatocellular Carcinoma, run by University Hospital, Montpellier at 19 sites in France.

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 21 inclusion and 40 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: under way, not looking for participants, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Recurrence-free survival (time frame: 2 years after randomization). 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 NCT04727307.

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 22 Jun 2026.

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