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

NCT04727307 | Recruiting Phase 2

• 3 other identifiers: RECHMPL20_00942024-519113-59-002020-000569-18
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 19

Brief 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 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.

Conditions

Hepatocellular Carcinoma

Keywords

Atezolizumab; Bevacizumab; Percutaneous radiofrequency; Ablation; Liver disease

Outcome Measures

Primary Outcomes (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.

  2 years after randomization

Study Arms (2)

Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + Bevacizumab

EXPERIMENTAL

Neoadjuvant atezolizumab and adjuvant atezolizumab + bevacizumab in combination with percutaneous radiofrequency ablation

Drug: Atezolizumab (neoadjuvant); Procedure: Percutaneous Radiofrequency; Drug: Bevacizumab (adjuvant); Drug: Atezolizumab (adjuvant)

Percutaneous radiofrequency ablation

ACTIVE COMPARATOR

Percutaneous radiofrequency ablation, standard treatment

Procedure: Percutaneous Radiofrequency

Interventions

Atezolizumab (neoadjuvant) DRUG

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.

Also known as: Tecentriq

Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + Bevacizumab

Percutaneous Radiofrequency PROCEDURE

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

Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + Bevacizumab; Percutaneous radiofrequency ablation

Bevacizumab (adjuvant) DRUG

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.

Also known as: Avastin 400 mg in 16 ml Injection, Avastin 100 mg in 4 ml Injection

Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + Bevacizumab

Atezolizumab (adjuvant) DRUG

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.

Also known as: Tecentriq

Neoadjuvant Atezolizumab before radiofrequency ablation then adjuvant Atezolizumab + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• nodules of HCC
• At least one uni-dimensional measurable lesion by magnetic resonance imaging (MRI) according to modified RECIST criteria
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (19)

CHU Amiens

Amiens, France

RECRUITING

CHU d'Angers

Angers, France

RECRUITING

Hôpital Jean Verdier

Bondy, France

RECRUITING

Hôpital Beaujon

Clichy, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

CHU Dijon

Dijon, France

RECRUITING

CHU de Grenoble

Grenoble, France

RECRUITING

CHU de Lille

Lille, France

NOT YET RECRUITING

Hôpital Saint Joseph

Marseille, France

RECRUITING

CHU de Montpellier

Montpellier, France

RECRUITING

CHRU de Nancy

Nancy, France

RECRUITING

CHU de Nantes

Nantes, France

RECRUITING

CHU de Nice

Nice, France

NOT YET RECRUITING

CHU Nîmes

Nîmes, France

RECRUITING

Hôpital Cochin

Paris, France

RECRUITING

CH Perpignan

Perpignan, France

RECRUITING

CHU de Poitiers

Poitiers, France

RECRUITING

CHU de Rennes

Rennes, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Diseases

Interventions

atezolizumab; Neoadjuvant Therapy; Catheter Ablation; Bevacizumab; Adjuvants, Pharmaceutic; Injections

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Radiofrequency Ablation; Radiofrequency Therapy; Ablation Techniques; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; Drug Administration Routes; Drug Therapy

Study Officials

• Boris GUIU, MD, PhD

  University Hospital, Montpellier

  STUDY DIRECTOR

Central Study Contacts

Wendy RENIER, PhD

CONTACT

+33 4 67 33 52 43; w-renier@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: January 27, 2021
• Study Start: February 23, 2021
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2031
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

FR (19)