NCT05970302招募中2 期
XELOX and Bevacizumab in Combination With Tislelizumab for First-Line Treatment of Patients With MSS/pMMR RAS-mutated Metastatic Colorectal Cancer (mCRC): A Single-arm, Phase II Study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences1 个研究点 分布在 1 个国家目标入组 52 人开始时间: 2023年7月7日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The goal of this clinical trial is to compare XELOX +Bev +Tislelizumab with standard chemotherapy，in MSS/pMMR-type RAS-mutated metastatic colorectal adenocarcinoma. The main questions it aims to answer are efficacy and safety of the regimen of XELOX +Bev +Tislelizumab. The investigators want to transform ras-mutated colorectal cancer into a "hot tumor" through the combination of anti-vascular therapy and chemotherapy, and then achieve better therapeutic effect through the combination with immunotherapy. Participants will receive the regimen of XELOX +Bev +Tislelizumab.
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
- •Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic colorectal adenocarcinoma;
- •ECOG score of 0 or 1;
- •Ability to swallow oral medications;
- •Have at least one measurable lesion (according to RECIST v1.1 standard);
- •No anti-tumor treatment has been received after recurrence and metastasis;
- •Neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before or after radical resection of colorectal cancer, but the treatment needs to be completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant chemotherapy, it includes The oxaliplatin regimen needs to be completed for ≥12 months;
- •Adequate organ function: On the premise of no component blood transfusion within 14 days: white blood cells ≥ 3.5*10^9/L and neutrophils ≥ 1.5*10^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100* 10^9/L; serum bilirubin ≤ 1.5 times the normal value, alanine aminotransferase (ALT) ≤ 2.5 times the normal value, aspartate aminotransferase (AST) ≤ 2.5 times the normal value; Urinary protein <2+. Or urine protein 2+ but 24-hour urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine clearance rate ≥ 60ml/min; Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%);
- •Expected survival period ≥ 3 months;
- •Patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent;
- •Women with reproductive potential (< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment.
排除标准
- •Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies or pathway-targeted drugs;
- •Received radiotherapy within 4 weeks before the evaluation;
- •Symptomatic peripheral neuropathy > grade 2 (CTCAE5.0 standard);
- •Received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month;
- •HIV-positive and other immunodeficiency diseases;
- •Active hepatitis B or hepatitis C (except for those who have been infected or cured before, that is, HBsAg negative and hepatitis B core antigen anti-HBc antibody positive; except for hepatitis C patients whose HCV RNA is negative by PCR);
- •Existing autoimmune diseases or other diseases that require immunosuppressant treatment, except for type 1 diabetes; except for hypothyroidism that only requires hormone replacement therapy; skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or equivalent steroids in excess of 10 mg prednisone per day, except for inactive autoimmune disease on adrenal replacement therapy;
- •Received systemic hormone therapy or treatment with a daily dose of more than 10 mg prednisone equivalent dose or other forms of immunosuppressive treatment within 7 days, but inhaled or topical steroids or daily application of more than 10 mg prednisone, etc. Except for inactive autoimmune diseases treated with adrenal replacement therapy with potent steroids;
- •Have a history of organ transplantation;
- •Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases;
- •Those who have undergone major surgery, open biopsy or obvious traumatic trauma within 1 month, or who may need major surgery during the study period; those who have undergone open biopsy or obvious traumatic trauma, or may need major surgery during the study period;
- •Combined with other malignant tumors other than intestinal cancer (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 1 year, and there is no clinical and imaging evidence of recurrence or progression except);
- •Combined active and refractory infection;
- •Cardiovascular diseases with clinical significance, such as cardiovascular accident (CVA) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before treatment), unstable angina, chronic heart failure of NYHA ≥ 2 (CHF), uncontrolled arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6 months before treatment;
- •Evidence of causing coagulation disease;
- •With dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction, active gastrointestinal bleeding, perforation, malabsorption syndrome or uncontrollable gastrointestinal inflammatory disease (such as Crohn's disease or ulcerative colon inflammation);
- •Severe unhealed wounds/ulcers or severe fractures;
- •Any serious acute or chronic medical condition that may affect the patient's participation in the study or interfere with the interpretation of the study results;
- •There are mental illnesses, serious social and psychological illnesses, or researchers believe that there are factors that may affect research compliance;
- •Pregnant or lactating women;
- •No therapeutic anticoagulant or antiplatelet drugs or NSAIDs (aspirin ≤ 325 mg/day allowed);
- •Severe allergic reaction to the test drug;
- •Reluctance to use alternative therapies such as (but not limited to) bisphosphonates if receiving RANKL inhibitors (eg, denosumab).
研究组 & 干预措施
XELOX +Bev +Tislelizumab
Experimental
Every 3 weeks as a cycle:
- Tislelizumab: 200mg, iv, d1;
- Bevacizumab: 7.5mg/kg, iv, d1;
- Oxaliplatin: 130mg/m2, iv, d1;
- Capecitabine: 1000mg/m2, bid, po, d1-d14; Re-evaluate patients every two cycles. If the patient has been treated for more than 8 cycles, they will enter maintenance therapy, and the regimen is capecitabine + BEV combined with tislelizumab.
干预措施: Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 2 years
ORR of regimen of XELOX +Bev +Tislelizumab
次要结局
- Duration of Response (DoR)(2 years)
- Disease Control Rate (DCR);(2 years)
- 12-month PFS rate(12 months)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](2 years)
- Median Progression-Free Survival (mPFS)(2 years)
- Median Overall Survival (mOS)(5 years)
研究者
LIN YANG
chief physician
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
研究点 (1)
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