Neoadjuvant and Adjuvant Nivolumab in HCC Patients Treated by Electroporation
Status:
Recruiting
Trial end date:
2023-11-30
Target enrollment:
Participant gender:
Summary
Percutaneous ablation (PA) is the only non-surgical curative treatment of hepatocellular
carcinoma (HCC). 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. For HCC less than 3 cm, ideal indication
for percutaneous ablations, results of monopolar radiofrequency ablation (mRFA), are
excellent with only 5% of reported non-tumoral control after a first procedure .
In addition to mRFA the arsenal of ablations has grown considerably with the emergence of new
techniques. They allow the expansion of indications for PA, especially in patients with poor
prognostic tumors or relatively advanced beyond the Milan criteria . In this setting,
multibipolar mode using no touch technique (mbpRFAnt) increases the tumour volume that can be
ablated, allowing the removal of large tumors> 5 cm . Furthermore, electroporation (EP) is a
new PA technique that does not promote thermoablation but induce tumoral cells apoptosis and
is particularly interesting for difficult-to-treat lesions located near vascular or biliary
trunks . Inadequate tumour control is then de facto greater in these situations, around 20%
at one year.
The idea of optimizing HCC curative treatments using neoadjuvant or adjuvant biotherapy,
particularly in patients with advanced tumors in curative intent, is particularly attractive.
One trial in adjuvant setting was conducted, the STORM trial, that tested the benefit of
sorafenib in curative intent of in Milan HCC. This negative trial included patients with in
Milan HCC, with an expected low rate of recurrence with only few patients treated by PA.
In parallel, the development of new molecules for HCC treatment, especially immunotherapy,
seems to give promising results in palliative setting . Furthermore, PA procedures and most
likely electroporation induce T-cell recruitement that may foster immunomodulation .
Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed
based on the rigorous selection of special populations and therapeutic indications.
This project proposes a Phase 2 trial testing the safety and efficacy of treatment with
Nivolumab in neoadjuvant and adjuvant setting in patients with advanced HCC treated by
electroporation in curative intent.