Phase II of Immunotherapy Plus Local Tumor Ablation (RFA or Stereotactic Radiotherapy) in Patients With Colorectal Cancer Liver Metastases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 10
- 主要终点
- Best overall immune response rate (iBOR) of lesions not treated by ablation/radiotherapy including the extrahepatic lesions according to iRECIST (with response confirmation)
研究概览
简要总结
This is a single-arm, open-label, multi-center early phase II study. This proof of concept study will investigate whether the combined use of local tumor ablation/radiation plus immunomodulating drugs may induce a significant immune response in patient with incurable liver metastases from colorectal cancer (CRC) (+/- limited extrahepatic disease) being stable or in partial remission after completion of 4-6 months first line systemic therapy.
The primary objective of the study is to show an overall response rate of lesions not treated by ablation/radiotherapy including the extrahepatic lesions (according to iRECIST criteria) higher than 10%. With the continuation of first line systemic treatment, no further responses are expected.
Secondary objectives are:
- To establish the feasibility and safety of the combined treatment modalities;
- To study the impact of the local technique (RFA/Radiotherapy) on the results;
- To investigate biomarkers to predict response to the combined treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
immunotherapy + local tumor ablation
Patients with unresectable colorectal liver metastases which show at least stable disease or partial remission after 4-6 months will receive treatment with durvalumab and tremelimumab plus local tumor ablation (Radiofrequency ablation RFA or Sterotactic body radiation therapy SBRT) of selected liver lesions, followed by maintenance treatment with durvalumab.
干预措施: Durvalumab (MEDI4736) (Drug)
immunotherapy + local tumor ablation
Patients with unresectable colorectal liver metastases which show at least stable disease or partial remission after 4-6 months will receive treatment with durvalumab and tremelimumab plus local tumor ablation (Radiofrequency ablation RFA or Sterotactic body radiation therapy SBRT) of selected liver lesions, followed by maintenance treatment with durvalumab.
干预措施: Tremelimumab (Drug)
immunotherapy + local tumor ablation
Patients with unresectable colorectal liver metastases which show at least stable disease or partial remission after 4-6 months will receive treatment with durvalumab and tremelimumab plus local tumor ablation (Radiofrequency ablation RFA or Sterotactic body radiation therapy SBRT) of selected liver lesions, followed by maintenance treatment with durvalumab.
干预措施: Sterotactic body radiation therapy (SBRT) (Radiation)
immunotherapy + local tumor ablation
Patients with unresectable colorectal liver metastases which show at least stable disease or partial remission after 4-6 months will receive treatment with durvalumab and tremelimumab plus local tumor ablation (Radiofrequency ablation RFA or Sterotactic body radiation therapy SBRT) of selected liver lesions, followed by maintenance treatment with durvalumab.
干预措施: Radiofrequency ablation (RFA) (Other)
结局指标
主要结局
Best overall immune response rate (iBOR) of lesions not treated by ablation/radiotherapy including the extrahepatic lesions according to iRECIST (with response confirmation)
时间窗: 36 months from first patient in
The statistical design is based on the assumption that the continuation of first line systemic treatment would result in nearly no further response translating into a response rate of 0 to 5% at maximum in the enrolled patient's population. A response rate of 10% in the experimental arm (local treatment + immunotherapy) will be judged too low to justify this combined approach. On the contrary, a response rate of 25% will be judged very promising. An optimal Simon's two-stage design will be used for the rejection of a 10% or less iBOR rate
次要结局
- Best overall immune response rate of liver lesions not treated with local therapy according to iRECIST (with response confirmation)(36 months from first patient in)
- Stable disease duration(54 months from first patient in)
- Overall survival(54 months from first patient in)
- Response duration(54 months from first patient in)
- Safety: Safety analyses will be performed on the Safety population. The worst toxicity grade per patient over the treatment period according to the CTCAE criteria version 4.0 will be displayed.(54 months from first patient in)
- Best overall response rate of lesions not treated by ablation/radiotherapy including or not the extrahepatic lesions according to RECIST v1.1 (with response confirmation)(36 months from first patient in)
- Progression free survival according to iRECIST and to RECIST v1.1(54 months from first patient in)