Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure
- Conditions
- HCC - Hepatocellular Carcinoma
- Interventions
- Drug: Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
- Registration Number
- NCT06045975
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
This project is a Phase 2 trial testing the safety and efficacy of treatment with Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting in patients with BCLC A HCC treated by by percutaneous ablation (PA) procedure in a curative intent.
DUMELEP is a Multicentre, Phase 2 trial
Eligible patients will receive consecutively:
1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting
2. percutaneous ablation procedure in a curative attempt at Day 30
3. 11 monthly Durvalumab 1500 mg infusions.
4. Classical follow-up during an additional year (every 3 months)
- Detailed Description
Immunotherapy is currently the gold standard for first-line treatment of advanced HCC based of the combination of check-point inhibitors (CPI). The first approved regimen is based on the association of atezolizumab and bevacizumab, an antiangiogenic molecule. More recently, the HIMALAYA trial demonstrated the superiority of durvalumab-tremelimumab over sorafenib, establishing a new first-line option.The combination of Immunotherapy and locoregional treatments in earlier HCC stages may reduce relapse rates. Preliminary data from the IMBRAVE 050 trail reports lower rates of recurrence following HCC percutaneous ablation (PA) or resection associated with atezolizumab and bevacizumab in adjuvant setting.PA procedures and most likely electroporation induce T-cell recruitment that may foster immunomodulation. In particular, radiofrequency ablation (RFA) can lead to stimulation of NK cells with a more differentiated and proactivatory phenotypic profile with general increase of functional activities. As compared with RFA, these local changes of IRE induce more robust systemic effects, including both tumorigenic and immunogenic events. Indeed, the preservation of the tumor microvasculature and extracellular matrix within the coagulated zone would favour infiltration by anti tumoral immune cells. These observations are relevant for development of neoadjuvant and adjuvant immunotherapeutic strategies in the setting of HCC treated by percutaneous ablation, and particularly IRE .
Neoadjuvant and adjuvant trials using these new molecules must now be cautiously designed based on the rigorous selection of special populations and therapeutic indications based on the following criteria:
* Exclusion of early forms of HCC with low probability of recurrence for statistical power issues
* Inclusion of patients with HCC treated in "curative intent" by new PA techniques such as electroporation
* Selective inclusion of patients treated with PA whose immunomodulatory properties are recognized
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Durvalumab/Tremelimumab Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
- Primary Outcome Measures
Name Time Method local recurrence-free survival 12 months after PA procedure Local recurrence is defined as the emergence of irregular areas enhanced at arterial phase followed by wash out at portal phase observed next to the ablation zone
- Secondary Outcome Measures
Name Time Method Changes of tumorous and non-tumorous perfusion parameters one month of neoadjuvant treatment rates of nodule(s) comprising necrosis and/or hypoperfusion radiological aspect compared before and after neoadjuvant course): analyzed as qualitative variables
Changes of size of nodules following neoadjuvant course one month of neoadjuvant treatment Nodule rates of early response after a single procedure of PA procedure (defined as absence of active tumor evaluated at one month following PA procedure)
Incidences of intra segmental/ extra segmental distant recurrence Throughout the study, an average of 30 months will be assessed using imaging techniques as recommended by international guidelines (3-months US and MRI)
Overall survival 12 months after PA procedure defined as patients who are alive with or without HCC recurrence 1 year after PA procedure. Date of death will be specified when applicable during this timeframe.
Treatment-related adverse events Throughout the study, an average of 30 months will be monitored according to manufacturer guidelines and recommendation.
Timeframe of PA performance one month of neoadjuvant treatment defined as number of days of delay in case of safety issues encountered
Compliance to neoadjuvant and adjuvant treatments during one cycle neoadjuvant treatment and 11 months starting after the PA evaluation Respect of scheduled Durvalumab/Tremelimumab infusions, Number of Durvalumab/Tremelimumab infusions administered
Safety of Durvalumab/Tremelimumab infusions Throughout the study, an average of 30 months Incidence of Adverse Events using current CTCAE
Trial Locations
- Locations (1)
Hospitl Avicenne
🇫🇷Bobigny, France