Liposomal Irinotecan + Leucovorin + 5-fluorouracil + Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer (IRIS)：a Multicenter, Single-arm, Prospective, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 173
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.
详细描述
Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. FOLFIRI (irinotecan+5-FU/LV) / FOLFOX (oxaliplatin+5-FU/LV) ± angiogenesis inhibitors are common treatments for advanced CRC. For patients receiving oxaliplatin-based therapy, irinotecan-based therapy is recommended as second-line therapy. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose, improve the efficacy and reduce the toxic side effects. The aim of this study is to explore the efficacy and safety of liposomal irinotecan+5-FU/LV + bevacizumab as second-line treatment for metastatic CRC.
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
- •Age: 18-75 years old.
- •Histologically or cytologically proven colon or rectum adenocarcinoma.
- •Confirmed as unresectable metastatic disease through radiological examination.
- •At least one measurable lesion (according to RECIST v1.1).
- •First-line treatment with oxaliplatin-based therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~
- •The expected survival time ≥3 months.
- •Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10^9/L.
- •Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present.
- •Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria <2+.
- •Normal coagulation function (INR≤1.5).
- •Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.
排除标准
- •Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
- •Previous treatment with irinotecan/liposomal irinotecan.
- •MSI-H/dMMR
- •Massive pleural effusion or ascites requiring intervention.
- •Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
- •Active HIV, HBV, HCV infection.
- •Combined with uncontrollable systemic diseases.
- •Presence of severe gastrointestinal disease (including active bleeding, > grade 1 obstruction , > grade 1 diarrhea or gastrointestinal perforation)
- •History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment.
- •Presence of interstitial pneumonia or pulmonary fibrosis.
- •Allergy to or intolerance to therapeutic drugs or their excipients;.
- •History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment.
- •Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment.
- •Patients with symptomatic central nervous system metastases.
- •Documented serum albumin ≤3 g/dL
- •Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A
- •Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
- •Participated in other trial within 30 days prior to the first dose of study treatment.
- •Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug
- •Patients who are not suitable to participate in this trial for any reason judged by the investigator.
研究组 & 干预措施
Experimental Group
liposomal irinotecan+5-FU/LV+ bevacizumab q2w
干预措施: 5-FU (Drug)
Experimental Group
liposomal irinotecan+5-FU/LV+ bevacizumab q2w
干预措施: liposomal irinotecan (Drug)
Experimental Group
liposomal irinotecan+5-FU/LV+ bevacizumab q2w
干预措施: LV (Drug)
Experimental Group
liposomal irinotecan+5-FU/LV+ bevacizumab q2w
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 4 months
Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.
次要结局
- Disease Control Rate(4 months)
- Progress-free survival(6 months)
- Duration of Response(4 months)
- Overall survival(1 year)
- Incidence of adverse events(5 months)