A Prospective Single-arm Phase Ib/II Study on the Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Progress-free Survival(PFS)
研究概览
简要总结
The prognosis of most patients with unresectable locally advanced or metastatic colorectal cancer (CRC) remains poor despite the advancements in chemotherapy and target therapy.
CAPability-01 trial investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer.
Based on the previous findings of CAPability-01, we will further evaluate the efficacy and safety of sintilimab and chidamide in combination with fruquintinib in the same setting.
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
- •Fully understand this study and voluntarily sign the informed consent form;
- •Age between 18-75 years inclusive;
- •Patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma;
- •Failure of standard second-line systemic treatment with measurable lesions;
- •Tumor tissue tested for microsatellite stability (MSS) or low microsatellite instability (MSI-L) by PCR, or confirmed pMMR by immunohistochemistry for DNA mismatch repair (MMR) protein (including MLH1, MSH2, MSH6, and PMS2 protein expression);
- •ECOG performance status of 0-2, with no deterioration within 7 days;
- •Expected survival ≥3 months;
- •Major organ functions meet the following requirements (no use of any blood components and growth factors within 14 days before enrollment):
- •Absolute neutrophil count ≥1.5×109/L, white blood cells ≥4.0×109/L;
- •Platelets ≥100×109/L;
- •Hemoglobin ≥90g/L;
- •Total bilirubin TBIL ≤1.5 times ULN;
- •ALT and AST ≤5 times ULN;
- •Urea/BUN and creatinine (Cr) ≤1.5×ULN (and creatinine clearance (CCr) ≥ 50mL/min);
- •Left ventricular ejection fraction (LVEF) ≥50%;
- •Corrected QT interval by Fridericia's formula (QTcF) <470 milliseconds.
- •INR ≤1.5×ULN, APTT ≤1.5×ULN.
- •Women of childbearing age must use effective contraception;
- •Good compliance and cooperation with follow-up.
排除标准
- •Unable to comply with the study protocol or procedures;
- •Pregnant or breastfeeding women;
- •Concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure;
- •Previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease;
- •Previous treatment with romidepsin;
- •Previous treatment with immune checkpoint inhibitors for metastatic disease;
- •Uncontrollable severe concurrent infections;
- •Acute myocardial infarction, acute coronary syndrome, or CABG within 3 months before the first treatment;
- •Subjects allergic to the study medication or any of its excipients;
- •Known human immunodeficiency virus (HIV) infection. Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×10^4 copies/mL or >2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (>1×10^3 copies/mL)];
- •Patients whom the investigator deems inappropriate for inclusion in this study.
研究组 & 干预措施
Study arm
Fruquintinib Sintilimab Chidamide
Treatments are administered until disease progression or toxicity intolerable.
干预措施: Fruquintinib (Drug)
Study arm
Fruquintinib Sintilimab Chidamide
Treatments are administered until disease progression or toxicity intolerable.
干预措施: Sintilimab (Drug)
Study arm
Fruquintinib Sintilimab Chidamide
Treatments are administered until disease progression or toxicity intolerable.
干预措施: Chidamide (Drug)
结局指标
主要结局
Progress-free Survival(PFS)
时间窗: 24 months
The time from enrollment until tumor progression or death from any cause, whichever occurred first
次要结局
- Objective response rate (ORR)(24 months)
- Overall Survival (OS)(24 months)
- Disease control rate (DCR)(24 months)
- Duration of response (DoR)(24 months)
研究者
Dai, Guanghai
Chief Physician
Chinese PLA General Hospital