Low-dose Trifluridine/Tipiracil With Bevacizumab in Refractory Metastatic Colorectal Cancer: a Multicenter, Single-arm, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- 6-month progression-free survival rate
研究概览
简要总结
This is a phase II, single-center, prospective trial aimed to investigate the efficacy and safety of a modified regimen of trifluridine/tipiracil plus bevacizumab in refractory metastatic colorectal cancer. Patients will be treated with trifluridine/tipiracil (17.5 mg/m2 dose orally twice daily, d1-10, every 14-days) plus bevacizumab (5mg/kg dose intravenously once at day 1, every 14-days). The study treatment will be administered until progression of disease, intolerable toxicity or withdraw of consent.
详细描述
The treatment options as third-line therapy for metastatic colorectal cancer patients are limited. Trifluridine/tipiracil (TAS-102) plus bevacizumab has been approved in colorectal cancer for patients who are refractory to or intolerant of standard chemotherapy. However, the toxicity of trifluridine/tipiracil at standard dose a clinical concerned issue. Modifications of dose and treatment cycle of trifluridine/tipiracil have been investigated, and show promising effect to reduce the toxicity. In this study, patients with refractory metastatic colorectal cancer who have disease progression after at least 2 standard regimens will be treated with low-dose trifluridine/tipiracil plus bevacizumab. Trifluridine/tipiracil will be given at a 17.5 mg/m2 dose orally twice daily in a 14-day cycle consisting of 10 treatment days/4 rest days. Bevacizumab will be given at a 5mg/kg dose intravenously once at day 1 in a 14-day cycle. This regimen will be administered until progression of disease, intolerable toxicity or withdraw of consent.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age over 60 years old, male and female
- •histologically confirmed adenocarcinoma of the colon or rectum
- •patients with metastatic or advanced unresectable diseases who had received two or more previous chemotherapy regimens or intolerance to last regimen
- •with or without measurable lesions
- •ECOG 0 to 2, expected survival time over 3 months
- •Enough organ functions that can tolerate treatment: Absolute neutrophil count (ANC) ≥1.5x109/L, White blood count ≥3.5x109/L, Platelets ≥75x109/L, Hemoglobin (Hb) ≥80g/L, ALT/AST ≤2.5x ULN (for patient with liver metastasis ALT/AST ≤5x ULN), Serum bilirubin ≤1.5x ULN, Serum creatinine ≤1.5x ULN.
- •Signed informed consent and willing to follow the study protocol
排除标准
- •symptomatic metastases of central nervous system
- •other primary malignancies
- •uncontrollable comorbidities, such as hypertension, thrombotic diseases, chronic kidney disease
- •organ functions that cannot tolerate study treatment
- •bowel obstruction or other conditions affecting oral administration
- •allergic to study medication
- •other conditions that patients are unsuitable for this study assessed by the investigators
研究组 & 干预措施
Experimental
Trifluridine/tipiracil 17.5 mg/m2 bid. po. d1-10, q2w Bevacizumab 5mg/kg ivgtt. d1 q2w
干预措施: Trifluridine/tipiracil (TAS-102) plus bevacizumab (Drug)
结局指标
主要结局
6-month progression-free survival rate
时间窗: 6 months
Defined as the proportion of patients who remain free from disease progression (as per RECIST criteria) or death for at least 6 months following initiation of study treatment.
次要结局
- Adverse events(through study completion, an average of 1 year)
- Objective response rate(up to 16 weeks)
- Progression free survival(From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months)
- Overall survival(From date of enrollment until the date of death from any cause, assessed up to 100 months)
研究者
Jun Zhang
Clinical Professor
Ruijin Hospital