A Single-arm, Open, Exploratory Clinical Study of Tislelizumab Combined With Radiotherapy as the Second-line Treatment of Advanced Biliary Malignant Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR) assessed according to RECIST v1.1
研究概览
简要总结
Biliary tract cancer (BTC) accounts for 4% of the malignant tumors of the digestive system, and the incidence has increased significantly in recent years. For advanced malignant tumors of the biliary tract, the existing treatment methods are very limited and the effective rate is low. At present, gemcitabine combined with platinum therapy is the first-line standard treatment for advanced biliary tract cancer. In recent years, tumor immunotherapy has made huge breakthroughs. There are also research attempts in advanced biliary tract cancer. A study published in the international top medical journal NEJM in 2015 showed that PD-1 monoclonal antibody treatment has mismatch gene repair defects. Patients with advanced biliary tract tumors have a higher curative effect. It suggests that PD-1 monoclonal antibody is worthy of in-depth study in the treatment of biliary tract tumors.
In the previous clinical studies of PD-1 in the treatment of biliary tract tumors conducted by our center, it was observed that the tumor control of some patients was stable with the combination of immunotherapy and radiotherapy. In view of the observations in the clinical research of our unit, relevant case reports, and the mechanism of the combination of radiotherapy and immunotherapy, we speculate that in patients with biliary tract cancer, radiotherapy and immunotherapy have a certain combined sensitization effect. Therefore, it is planned to carry out clinical research on the second-line treatment of advanced biliary tract cancer with radiotherapy and immunotherapy.
This study will explore the effectiveness and safety of tislelizumab combined with radiotherapy in the treatment of patients with advanced biliary malignant tumors (BTC) in second-line and above, with a view to improving the therapeutic effect of biliary tract tumors.
详细描述
Patient recruitment Research and discussion by the MDT team of the Department of Hepatobiliary Surgery of our center: Choose pathologically confirmed malignant tumors of the biliary tract that are inoperable or recurring after surgery, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer; patients with non-extensive metastases, after full communication with the patient, The patients joined the study after signing the informed consent form voluntarily.
During the study Each period of the test period is defined as 3 weeks. After starting tislelizumab, tumor imaging evaluation will be performed every 6 weeks (±7 days). Until the disease progresses or treatment ends.
Radiation Therapy We use intensity-modulated radiotherapy (IMRT) or stereotactic radiotherapy (SBRT) based on comprehensive factors such as the location of the lesion, the irradiation volume, the volume of the normal liver, liver function, and the general condition of the patient. The divided dose is within 3-7.5Gy. The number of divisions is between 2-15. Daily irradiation from Monday to Friday/week, or every other day on Monday, Wednesday, and Friday/week, strive to achieve a relative biological dose (BED) of more than 40Gy, and the exposure to organs at risk within the accepted range.
medical treatment On the 7th day (±3 days) after the start of radiotherapy, tislelizumab was given 200 mg, IVD, q3w, and continued treatment until disease progression, unacceptable toxic radiotherapy, death or meet any discontinuation criteria described in the protocol.
Follow up Safety follow-up Regardless of whether the patient starts a new anti-tumor therapy, the patient should be contacted 30 days (± 7 days) after the last dose of tislelizumab to assess irAE and concomitant medications.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathological diagnosis of Advanced biliary malignancy
- •The expected survival period is ≥3 months
- •Patients with non-extensive metastases
- •Except for the lesions to be radiotherapy, there is at least one measurable lesion
- •tumor lesions are suitable for radiotherapy
- •Have previously received platinum, gemcitabine or 5-FU drugs as first-line treatment, but have not used PD-1/PD-L1 monoclonal antibody treatment
- •In the 7 days before enrollment, the Child Pugh score of liver function is 7 or less
排除标准
- •Patients with other malignant tumors
- •Participated in other drug clinical trials within four weeks
- •Clinical diagnosis of severe biliary obstruction or digestive tract obstruction in the past month
- •Unstable angina pectoris
- •Immunodeficiency
- •Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia
- •Patients who need to use corticosteroids
- •Serious chronic autoimmune diseases
- •Ulcerative enteritis, Crohn's disease and other inflammatory bowel diseases
- •Inflammatory and chronic diarrheal diseases such as irritable bowel syndrome;
- •Sarcoidosis or tuberculosis
- •Patients with hypersensitivity to human or murine monoclonal antibodies
- •Pregnant and lactating women
结局指标
主要结局
Objective response rate (ORR) assessed according to RECIST v1.1
时间窗: 2 years
In this trial, the International Standard (Version 1.1) developed by the entity Tumor Equipment Assessment Standard (Recist) will be used to assess objective response rate (ORR) .
次要结局
- 6-month OS(6 months)
- Progression-Free Survival, PFS(2 years)
- Tumor size(2 years)