Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure in Curative Intent: French Multicenter Phase 2 Therapeutic
概览
- 阶段
- 2 期
- 干预措施
- Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
- 疾病 / 适应症
- 未指定
- 发起方
- Assistance Publique - Hôpitaux de Paris
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- local recurrence-free survival
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
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 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting
- percutaneous ablation procedure in a curative attempt at Day 30
- 11 monthly Durvalumab 1500 mg infusions.
- Classical follow-up during an additional year (every 3 months)
详细描述
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
研究者
入排标准
入选标准
- •\* Male or female patients ≥ 18 years of age.
- •\* Histological or radiological diagnosis of HCC
- •\* Patients with newly diagnosed or recurrent HCC (following a previous curative procedure performed at least 6 months before inclusion) eligible for PA as assessed by multidisciplinary board corresponding to BCLC A stage:
- •\* Uninodular HCC ≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion
- •\* Multinodular maximum 3 nodules ≤ 3 cm
- •\* Body weight \\\>30 kg
- •\* Liver function status Child\-Pugh Class A
- •\* Eastern Cooperative Oncology Group (ECOG) \-World Health Organisation (WHO) performance status of 0 or 1
- •\* Adequate bone marrow, liver and renal function as assessed by the following laboratory tests:
- •\* Total bilirubin ≤ 2 mg/dL
排除标准
- 未提供
研究组 & 干预措施
Durvalumab/Tremelimumab
Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
干预措施: Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting
结局指标
主要结局
local recurrence-free survival
时间窗: 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
次要结局
- Changes of tumorous and non-tumorous perfusion parameters(one month of neoadjuvant treatment)
- Changes of size of nodules following neoadjuvant course(one month of neoadjuvant treatment)
- Incidences of intra segmental/ extra segmental distant recurrence(Throughout the study, an average of 30 months)
- Treatment-related adverse events(Throughout the study, an average of 30 months)
- Timeframe of PA performance(one month of neoadjuvant treatment)
- Compliance to neoadjuvant and adjuvant treatments(during one cycle neoadjuvant treatment and 11 months starting after the PA evaluation)
- Safety of Durvalumab/Tremelimumab infusions(Throughout the study, an average of 30 months)
- Overall survival(12 months after PA procedure)