Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence: A Randomized Controlled Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
This study is a randomized controlled phase II trial to evaluate the efficacy of the combination of stereotactic body radiation therapy (SBRT) and immunotherapy with postoperative chemotherapy in colorectal cancer liver metastasis (CRLM) patients with high risk of locally recurrence. Researchers will compare the combination therapy with the postoperative chemotherapy alone to see if postoperative chemotherapy plus SBRT and immunotherapy can further reduce the risk of recurrence and metastasis after surgery.
详细描述
40-50% of colorectal cancer patients have metastases at the time of diagnosis, of which liver metastases are the most common. Surgical resection is the most likely cure for CRLM patients, however, more than 50% of patients will experience recurrence within 2 years after resection of liver metastases. SBRT can be an effective and safe treatment modality, which can not only provide better local control of metastatic lesions, but also has a sensitizing immunotherapeutic effect. SBRT can effectively synergize with anti-PD-1/PD-L1 antibodies to activate the immune microenvironment of CRLM patients and improve survival. However, in CRLM patients after surgery, whether combining SBRT, immunotherapy and adjuvant chemotherapy results in better survival than chemotherapy alone, the evidence is insufficient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •age ≥ 18 years old, female and male
- •pathological and imaging confirmed colorectal colorectal liver metastases (synchronous or heterochronous)
- •Metastatic liver lesions <= 5
- •Primary colorectal cancer under control
- •Absence of evidence of extra-hepatic diseases
- •Metastatic liver lesions received resection with insufficient margin (<0.5cm) or R1/R2 resection
- •Karnofsky >= 70
- •Adequate organ function without contraindications to surgery, radiotherapy and immunotherapy
- •Without previous antitumoral immunotherapy
- •With good compliance
- •Signed the inform consent
排除标准
- •Pregnancy or breast-feeding women
- •History of other malignancies within 5 years (except cured skin cancer and cervical cancer in situ)
- •History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders
- •Clinically serious heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
- •Immunodeficiency disease, autoimmune diseases or long-term using of immunosuppressive agents
- •Severe uncontrolled recurrent infections
- •Baseline blood and biochemical indicator do not meet the following criteria: neutrophils >=1.5×10^9/L, Hb >=90g/L, PLT >=100×10^9/L, ALT/AST<=2.5 ULN, Cr <= 1ULN
- •Allergic to any component of the therapy
研究组 & 干预措施
chemotherapy with radiotherapy and immunotherapy
radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
干预措施: SBRT (Radiation)
chemotherapy with radiotherapy and immunotherapy
radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
干预措施: Chemotherapy (Drug)
chemotherapy with radiotherapy and immunotherapy
radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
干预措施: PD-1 antibody (Drug)
chemotherapy
postoperative chemotherapy: chemotherapy by investigators' choice for 18 weeks
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Progression free survival
时间窗: From the date of randomization until the date of first documented progression or date of death from any cause, whichever come first, assessed up to 12 months
Evaluate the effect of the combination of adjuvant chemotherapy, SBRT and immunotherapy versus observation on progression free survival
次要结局
- Local control rate(From the date of randomization until the date of first documented locally tumor recurrence, assessed up to 12 months)
- Overall survival(From date of randomization until the date of death from any cause, assessed up to 36 months)
- Grade 3-4 adverse effect rate(From date of randomization until the date of death from any cause, assessed up to 3 years)
研究者
Lu Wang, MD, PhD
Professor
Fudan University