The Efficacy and Safety of Lcaritin Combined With Bevacizumab and FOLFIRI in Treatment of Liver Metastases From Colorectal Cancer: A Prospective, Single-arm Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Progression-free survival(PFS)
研究概览
简要总结
To evaluate the efficacy and safety of the combination regimen of Icaritin with bevacizumab + FOLFIRI in patients with liver metastases from advanced colorectal cancer.
详细描述
At present, second-line only targeting combined with chemotherapy is the main treatment option, and the choice of treatment modality is limited, with the immunotherapy rise of immunotherapy, the mode of combining immunotherapy on the basis of existing first- and second-line chemotherapy combined with targeting is also being actively explored, but no positive results of large-scale phase III clinical studies have been reported yet. Meanwhile, there is no solution to the the problem of pro-inflammatory factor release. Therefore, it is necessary to consider the combination of a drug with a better safety profile and target-immunity synergistic effect. A combination of drugs with better safety and target-immunity synergistic effect could be considered as a safer and more effective treatment option for patients with liver metastases from advanced colorectal cancer.
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
- •. Age ≥ 18 years. 2).Patients with unresectable advanced metastatic colorectal cancer confirmed by clinical diagnostic criteria and/or histopathological or cytological examination. Metastases include, but are not limited to the liver.
- •. Presence of clearly measurable (RECIST 1.1 compliant) liver metastases on imaging assessment (unresectable by MDT assessment).
- •. Patients who have failed prior first-line systemic systemic therapy, including bevacizumab.
- •.ECOG PS score 0-
- •. Have normal organ function and meet the following criteria on laboratory tests within 7 days prior to initiation of therapy:
- •Haemoglobin level > 80 g/L;
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
- •Platelet count ≥50×10-9/L;
- •Serum albumin ≥ 30 g/L;
- •Total bilirubin ≤ 2 × upper limit of normal (ULN);
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 5 × ULN;
- •Alkaline phosphatase (ALP) ≤ 2.5 x ULN;
- •creatinine ≤ 1.5 x ULN and creatinine clearance ≥ 50 ml/min. 7). Good swallowing function. 8). Coagulation function: international normalised ratio (INR) ≤ 1.5 x ULN or prothrombin time (PT)≤16s.
- •. Life expectancy ˃3 months. 10). Voluntary participation in this study and voluntary signing of informed consent.
- •. Men and women of gestational age must agree to use adequate contraception throughout the study and for 3 months after the end of treatment.
排除标准
- •. Pre-existing or coexisting other active malignant tumours (except for malignant tumours that have been curatively treated and have been free of malignancy that has received curative treatment and has been free of morbidity for more than 5 years or carcinoma in situ that can be cured by adequate treatment).
- •. Concomitant administration of modern Chinese medicinal preparations for antitumour and anti-tumour indications.
- •. Patients who have received chemotherapy or anti-vascular endothelial growth factor receptor (VEGF) therapy.
- •. Patients receiving systemic chemotherapy, hormonal therapy, immunotherapy, approved proteins/antibodies or any experimental drugs or treatments (30 days) or radiotherapy (within 14 days).
- •. Tumour invasion of large blood vessels. 6). Significant cardiovascular compromise within 12 months prior to the first dose of study drug: e.g., New York Heart Association (NYHA) Class II or higher. Stroke, myocardial infarction or cerebral haemorrhage, or arrhythmia associated with haemodynamic instability; Corrected QT (QTc) interval prolongation >480ms.
- •. Any surgical procedure within the last 28 days. 8). Bleeding from ruptured oesophageal or gastric varices within the last 2 weeks, or unconfirmed severe varices and bleeding in the judgement of the investigator.
- •. Bleeding or thrombotic disorders or on thrombolytic therapy, coagulation disorders; study intervention Clinically significant haemoptysis or tumour bleeding of any cause within 2 weeks prior to first dose.
- •. Patients with uncontrolled epilepsy, history of central nervous system disease or psychiatric disorders, hypertension.
- •. Active autoimmune disease requiring systemic therapy within the past 2 years.
- •. Clinically significant ascites on physical examination that cannot be controlled medically.
- •. Pregnant or breastfeeding female patients, or those unwilling to use contraception during the trial.
- •. Known hypersensitivity to Icaritin, Bevacizumab and chemotherapeutic drug components.
- •. Suspect that it may cause contraindication to the use of the drug, or affect the reliability of the study results, or place the patient at a disease or condition that places the patient at high risk for treatment complications, or affects the patient's adherence to the trial medication.
- •. Vulnerable populations, including those with mental illness, cognitive impairment, critically ill patients, illiteracy, etc.
- •. Presence of other reasons that the investigator considers inappropriate for participation in this study.
研究组 & 干预措施
Icaritin Combined With Bevacizumab and FOLFIRI
Icaritin: 600 mg orally, bid; Bevacizumab: Intravenous infusion, 5 mg/kg per dose, every 14 days; FOLFIRI: ①Irinotecan: Irinotecan should be given on the first day of chemotherapy at a dose of 180mg/m2 by intravenous drip.The infusion time should be >30-90min.
②Calcium folinate: give irinotecan at a dose of 400mg/m2 by intravenous drip in conjunction with irinotecan infusion, and the infusion time should be up to 2h.
③5-fluorouracil: give intravenous infusion at a dose of 400mg/m2 on the first day of chemotherapy, then give an intravenous drip at a dose of 1200mg/m2 for 2 days, the total amount of 2400mg/m2 , and continue to be infused for 46-48h.
干预措施: Icaritin Combined With Bevacizumab and FOLFIRI (Drug)
结局指标
主要结局
Progression-free survival(PFS)
时间窗: up to 5 years
Time between the start of the trial and the onset of (any aspect of) tumour progression or death (from any cause).
次要结局
- Overall survival (OS)(up to 5 years)
- Disease Control Rate (DCR)(up to 5 years)
- Quality of life of the patients(up to 5 years)
- Objective remission rate (ORR)(up to 5 years)
- TRAEs(up to 5 years)
- Duration of ongoing remission (DOR)(up to 5 years)
研究者
Sheng Dai
Principal Investigator, head of medical affairs
Sir Run Run Shaw Hospital