Exploratory Study on the Efficacy and Safety of Long-course Neoadjuvant Chemoradiation With Liposomal Irinotecan and Capecitabine Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response
研究概览
简要总结
This single-arm trial will explore the efficacy and safety of long-course neoadjuvant chemoradiation with liposomal irinotecan and capecitabine guided by UGT1A1 status in patients with locally advanced rectal cancer.
详细描述
This is a single-center, single-arm, prospective clinical study. The aim of this study is to explore the short-term and long-term efficacy and safety of total neoadjuvant therapy with irinotecan liposome in patients with locally advanced rectal cancer. Patients' nutritional status, quality of life, changes in symptoms, and adverse events will also be regularly assessed and registered during the implementation phase of the study, and patients will be treated promptly if symptoms are assessed as positive.
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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0~
- •Histopathologically confirmed rectal adenocarcinoma.
- •The lower edge of the primary tumor is located below the peritoneal reflection or located ≤ 10 cm above the anal verge.
- •Clinical stage: T3-4NanyM0 or T1-2N+M
- •Adequate bone marrow function as evidenced by: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin (Hb) ≥90 g/L.
- •Adequate hepatic function as evidenced by: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN, Serum albumin ≥3 g/dL.
- •Adequate renal function as evidenced by: Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min.
- •Be willing to undergo UGT1A1 gene testing and UGT1A1 genotype of *1*1 or *1*
- •Accept the neoadjuvant chemoradiotherapy protocol of this study and sign the informed consent.
排除标准
- •Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
- •Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
- •Active HIV infection.
- •Combined with uncontrollable systemic diseases.
- •History of allergy or hypersensitivity to drug or any of their excipients.
- •Any clinical indicators indicating contraindications to radiotherapy/chemotherapy and surgery.
- •Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A
- •Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
- •Patients with poor cognitive abilities who are unable to answer questions, fill out questionnaires, or have mental disorders.
- •Patients who do not meet the inclusion criteria; patients who meet the inclusion criteria but are not suitable to participate in this trial judged by the investigator.
研究组 & 干预措施
Liposomal irinotecan-based TNT therapy
Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m^2 bid + Liposomal irinotecan 50mg/m^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m^2 bid d1-7 + Liposomal irinotecan 70mg/m^2 or 50mg/m^2, d1, Q2W) before surgery.
干预措施: liposomal irinotecan (Drug)
Liposomal irinotecan-based TNT therapy
Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m^2 bid + Liposomal irinotecan 50mg/m^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m^2 bid d1-7 + Liposomal irinotecan 70mg/m^2 or 50mg/m^2, d1, Q2W) before surgery.
干预措施: Radiation threapy (Radiation)
Liposomal irinotecan-based TNT therapy
Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m^2 bid + Liposomal irinotecan 50mg/m^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m^2 bid d1-7 + Liposomal irinotecan 70mg/m^2 or 50mg/m^2, d1, Q2W) before surgery.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Pathologic Complete Response
时间窗: 1 week after sugery
Defined as the proportion of patients who have achieved pathologic complete response.
次要结局
- clinical complete response(up to 30 weeks)
- Incidence of adverse events(7 months)
- 3-year Local Recurrence Free Survival Rate(3 years)
- Major Pathologic Response(1 week after sugery)
- Objective Response Rate(through study completion，an average of 3 year)
- Anal Sphincter Retention Rate(1 week after sugery)
- 3-year Progress Free Survival Rate(3 years)
- R0 resection rate(1 week after sugery)
- 3-year Overall Survival Rate(3 years)