Neoadjuvant and Adjuvant Nivolumab in HCC Patients Treated by Electroporation — NIVOLEP  

Hepatocellular Carcinoma Clinical Trial

Official title: Immunotherapy by Nivolumab in Neoadjuvant and Adjuvant Setting in Patients With Advanced HCC Treated by Electroporation in Curative Intent: French Multicenter Phase 2 Therapeutic Trial.

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

Multicenter (6 centers), Phase 2 trial.

-Inclusion visit The inclusion visit takes place between 15 days and no later than 3 days before the patient's hospitalization for Neoadjuvant therapy

Eligible patients will receive :

• 2 nivolumab infusions in a neoadjuvant setting (every 15 days) The treatment will be carried out every 2 weeks s, for 2 cycles before EP procedure The patient is hospitalized one day for treatment

• EP procedure performed in a curative attempt EP procedure will be performed according to previously described procedure in the setting of routine management of HCC as decided in multidisciplinary boards in each centre.

• 12 nivolumab infusions in an adjuvant setting (every 30 days) during one year. The patient is hospitalized one day for infusion

• Classical follow-up during an additional year (every 3 months) Follow up after adjuvant therapy (M12-M24) The usual evaluation will be performed every 3 months

Constitution of a biobank with :

• paraffin and frozen tumoral and non tumoral biopsy sampled at before and after one month of neoadjuvant Nivolumab (second biopsies at the time of the electroporation procedure)

• Serum samples and Peripheral blood mononuclear cells (PBMC) before and after one month of neoadjuvant Nivolumab then after EP at 1, 3, 6, 9 and 12 months after procedure. ;

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

• NCT number: NCT03630640
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 11, 2018
• Completion date: November 30, 2023