A Single-center, Single-arm, Open-label Clinical Study of Fruquintinib Combined With Tislelizumab and HAIC in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- objective response rate (ORR)
研究概览
简要总结
This is a single-center, single-arm, open-label clinical study, to explore the efficacy and safety of fruquintinib combined with tislelizumab and HAIC (hepatic arterial infusion chemotherapy) in patients with colorectal liver metastases cancer (CRLM) who failed standard therapy.
详细描述
Liver is the most common metastatic site in patients with colorectal cancer (CRC) and the leading cause of death in patients. Surgery is the best way to cure CRLM, but few patients can receive surgery, and patients prone to recurrence after surgery. It is an urgent topic to choose an effective treatment method with less side effects for CRLM patients. HAIC is a unique and effective treatment option for CRLM patients. Fruquintinib is a small molecule angiogenesis inhibitor, and has been recommended for third-line treatment of metastatic colorectal cancer (mCRC). Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, meanwhile, tislelizumab shows significant and durable antitumor activity in patients with CRC, and is well tolerated.
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
- •Informed consent has been signed
- •Histologically or cytologically confirmed unresectable advanced colorectal liver metastases cancer
- •Age ≥ 18 years, ≤75 years
- •ECOG PS：0-1
- •Expected overall survival ≥3 months
- •Patients must have at least one measurable liver metastases (RECIST 1.1)
- •Patients who have previously failed standard treatment, or who cannot tolerate standard treatment
- •Patients must have adequate organ and bone marrow function
- •Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration
排除标准
- •Patients who are allergic or suspected to be allergic to the study drug or similar drugs
- •Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
- •Participating in other clinical trials and received at least one treatment within 4 weeks before enrollment
- •Patients with autoimmune disease or history of autoimmune disease within 4 weeks before enrollment
- •patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months
- •Patients cannot take fruquintinib orally
- •Patients who have received organ transplantation and bone marrow transplantation in the past
- •Have taken other strong inducers or inhibitors of CYP3A4, P-gp substrates and BCRP substrates within 2 weeks before the First medication
- •Received any operation (except biopsy) or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before enrollment
- •Pleural effusion or ascites causing relevant clinical symptoms, including respiratory syndrome (dyspnea≥CTC AE grade 2)
- •Clinically significant electrolyte abnormality；
- •Systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless of any antihypertensive drugs; Or patients need more than two antihypertensive drugs
- •Proteinuria ≥ 2+ (1.0g/24hr);
- •Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage in GI, or other conditions that may cause GI bleeding and perforation as determined by the investigator;
- •Have evidence or history of bleeding tendency within 3 months or thromboembolic events within 12 months before enrollment
- •Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; NYHA classification > 2 Grade; ventricular arrhythmia requiring medical therapy; ECG showing QTc interval ≥ 480 ms
- •Active or uncontrolled serious infection (≥CTCAE grade 2 infection)
- •Pregnant or lactating women
- •Any other disease, with clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the judgment of investigator that the patient is not suitable for the the study drug (such as having epileptic seizures and require treatment), or would affect the interpretation of study results, or put patients at high risk
- •Clinical uncontrolled active infections, including human immunodeficiency virus (HIV) infection, active hepatitis B / C (HBV DNA Positive[1×104 copies/mL or >2000 IU/ml], HCV RNA positive[>1×103 copies/mL]);
- •Patients have other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental diseases) that require concomitant treatment, and serious laboratory abnormalities. Accompanied by family or social factors, which will affect the safety of patients.
研究组 & 干预措施
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: HAIC (Procedure)
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: Fruquintinib (Drug)
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: Tislelizumab (Drug)
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: Raltitrexed (Drug)
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: Oxaliplatin (Drug)
combination therapy
Combination: Fruquintinib plus Tislelizumab and HAIC (TOMOX/TOMIRI)
Maintenance: Fruquintinib plus Tislelizumab
干预措施: Irinotecan (Drug)
结局指标
主要结局
objective response rate (ORR)
时间窗: 24 months
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
次要结局
- overall survival (OS)(24 months)
- Progression-Free Survival (PFS)(24 months)
- Adverse events as assessed by NCI CTCAE v5.0(24 months)
- disease control rate (DCR)(24 months)
- Progression-Free Survival rate at 6 months(6 months)
研究者
Lu Wang, MD, PhD
Head of liver surgery department
Fudan University