A Phase Ib Trial on the Safety and Feasibility of Low Dose Radiotherapy (LDRT) Combined With Immunochemotherapy for Colorectal Cancer With Liver-limited Metastasis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
In recent years, growing evidences have demonstrated promising synergistic antitumor effects of radiotherapy combined with immunotherapy. More over, LDRT may enhance the antitumor effect of immunotherapy by altering the tumor immune microenvironment (TIME) and adjusting the immune response. In this study, we will explore the safety and feasibility of LDRT and immunochemotherapy in liver metastatic colorectal cancer. 9-18 participants will be enrolled in this study. All will take part at Daping Hospital, Army Medical University.
详细描述
This is a prospective, single-arm, phase Ib trial. At least 9 eligible patients will be will be enrolled In this study. Patients will receive LDRT of 10 Gy in 5 fractions, 15 Gy in 5 fractions, 20 Gy in 10 fractions respectively in our three groups on liver metastsis from Day1 (patients with rectal cancer will receive SCRT concurrently), followed by Xelox and Tislelizumab starting from 1 week after the completion of radiation. The primary endpoints are safety and tolerability.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between18 and 75 years old.
- •Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
- •The clinical baseline stage of rectal cancer assessed by MRI/CT/Transrectal ultrasound was T3-4Nx or TXN1-
- •Simultaneous liver metastasis confirmed by imaging examination.
- •No previous antitumor treatment.
- •An Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate cardiac function (Left Ventricular Ejection Fractions > 50%), hepatic function (total serum bilirubin ≤ 1.5 × upper limit of normal, alanine aminotransferase or aspartate aminotransferase ≤ 2.5 × upper limit of normal), renal function (serum creatinine ≤ 1.5 × ULN or glomerular filtration rate > 60 ml/min, based on Cockcroft-Gault), and hematopoietic function (white blood cells ≥ 4.0 × 109 cells per L, neutrophils ≥ 1.5 × 109 cells per L, hemoglobin ≥ 90 g/L, platelets ≥ 100 × 109 cells per L).
- •Sign the informed consent and have good compliance.
排除标准
- •Distant metastasis from other than the liver.
- •BMI < 18.5 kg/m² or weight loss ≥ 10% within the past 6 months (with consideration of the impact of large amounts of pleural and ascitic fluid on body weight).
- •Received any of the following treatments: any investigational drug; enrolled in another clinical trial concurrently, unless it is an observational (non-interventional) clinical study; received anti-tumor vaccines or live vaccines.
- •Active autoimmune diseases, or a history of autoimmune diseases. A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver cirrhosis.
- •History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation.
- •A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%).
- •The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
- •Pregnant or lactating women.
- •The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
研究组 & 干预措施
LDRT/LDRT+SCRT followed by Tislelizumab+XELOX
For patients with colon Cancer:
LDRT starts from day 1.
For patients with rectal Cancer:
LDRT and SCRT start concurrently from day 1. Tislelizumab+XELOX start from 1week after the completion of radiotherapy (2-4 cycles).
干预措施: Low Dose Radiotherapy (Radiation)
LDRT/LDRT+SCRT followed by Tislelizumab+XELOX
For patients with colon Cancer:
LDRT starts from day 1.
For patients with rectal Cancer:
LDRT and SCRT start concurrently from day 1. Tislelizumab+XELOX start from 1week after the completion of radiotherapy (2-4 cycles).
干预措施: Short course Radiotherapy (Radiation)
LDRT/LDRT+SCRT followed by Tislelizumab+XELOX
For patients with colon Cancer:
LDRT starts from day 1.
For patients with rectal Cancer:
LDRT and SCRT start concurrently from day 1. Tislelizumab+XELOX start from 1week after the completion of radiotherapy (2-4 cycles).
干预措施: XELOX (Drug)
LDRT/LDRT+SCRT followed by Tislelizumab+XELOX
For patients with colon Cancer:
LDRT starts from day 1.
For patients with rectal Cancer:
LDRT and SCRT start concurrently from day 1. Tislelizumab+XELOX start from 1week after the completion of radiotherapy (2-4 cycles).
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: 3 years
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measurement of Safety and tolerability of LDRT in Combination With Tirellizumab and XELOX
次要结局
- Objective Response Rate (ORR)(2 years)
- Progression-free survival (PFS)(2 years)
- Overall survival (OS)(3 years)