Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Bevacizumab

Atezolizumab

Liver Extracts

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Immunologic Factors

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

Percutaneous radiofrequency ablation, standard treatment

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.

Atezolizumab (neoadjuvant)

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

Percutaneous Radiofrequency

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.

Bevacizumab (adjuvant)

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.

Atezolizumab (adjuvant)

Wendy RENIER, PhD

Eric NGUYEN-KHAC, MD

Thierry YZET, MD

Jérôme LEBIGOT, MD

Frédéric OBERTI, MD

Pierre NAHON, MD

Olivier SEROR, MD

Maxime RONOT, MD

Mohamed BOUATTOUR, MD

François GHIRINGHELLI, MD

Nathalie MEJEAN, MD

Romaric LOFFROY, MD

Sylvain MANFREDI, MD

Thomas DECAENS, MD

Julien GHELFI, MD

Géraldine SERGENT, MD

Stéphane CATTAN, MD

Olivier MONNET, MD

Xavier ADHOUTE, MD

Boris GUIU, MD, PhD

Eric ASSENAT, MD, PhD

Valérie CROISE-LAURENT, MD

Jean-Pierre BRONOWICKI, MD

Yann TOUCHEFFEU, MD

Jérémy MEYER, MD

Patrick CHEVALLIER, MD

Rodolphe ANTY, MD

Julien FRANDON, MD

Valérie PHOUTTHASSANG, MD

Anthony DOHAN, MD

Clémence HOLLANDE, MD

Faiza KHEMISSA, MD

Geoffroy FAROUIL, MD

Jean-Pierre TASU, MD

Claire BOYER, MD

Vanessa BRUN, MD

Thomas UGUEN, MD

Thierry DE BAERE, MD

Valérie BOIGE, MD

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.

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.

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

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

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.

University Hospital, Montpellier

Spots Global Cancer Trial Database for atezolizumab (adjuvant)