The Efficacy and Safety of TACE Combined With Arginine Hydrochloride and Trimetazidine Hydrochloride Tablets in With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Progression-free Survival
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with arginine hydrochloride and trimetazidine hydrochloride tablets in the treatment of patients with hepatocellular carcinoma.
详细描述
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related deaths in the world. Because HCC is insidious and early diagnosis is difficult, most patients have locally advanced or distant metastasis at the time of diagnosis. So they are not suitable candidates for curative treatments by resection or transplantation. Currently, Sorafenib is the only choice approved by FDA for advanced HCC, although it prolongs the survival for less than 3 months. Transarterial chemoembolization (TACE) is an important method of minimally invasive therapy in the comprehensive treatment of liver cancer. As a kind of combined treatment, it can obviously prolong the survival time of the patients. Recently, metabolomics studies of HCC have shown that typical Warburg effect was observed in hepatoma carcinoma cells. Arginine hydrochloride is a new anticancer drug in the treatment of liver cancer, which is mainly aimed at the pathway of energy metabolism. Trimetazidine hydrochloride may play an anti-tumor role by inhibiting fatty acid oxidation. The investigators have been proceeding this trial to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with arginine hydrochloride and trimetazidine hydrochloride tablets in the treatment of patients with hepatocellular carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18-65 years
- •The diagnosis of HCC: in accordance with "diagnostic and treating standards on primary liver cancer" (2011 Edition) or histological/cytological diagnosis of primary liver cancer
- •Un-resectable HCC who are eligible for TACE: patients with developing primary liver cancer of Barcelona stage(BCLC) B; multiple nodules (less than 5, the total diameter of less than 20 cm), no invasion, no symptoms; refusing open surgical treatment and volunteering for the treatment
- •There are CT or MRI measurable lesions
- •No major vascular invasion or extra hepatic metastasis
- •Child-Pugh liver function class A/B(score: ≤7)
- •Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale in one week before admission
- •Estimated survival time > 3 months
- •HBV DNA<2000 IU/ml（10^4 copies/ml); or HBV DNA≥2000 IU/ml and are accepting effective antiviral therapy
- •The major organ function is normal. that is meeting the following standards:
- •Blood routine examination: (No blood transfusion, no G-CSF and no medication were corrected within 14 days before screening)
- •a.HB≥80g/L； b.ANC≥1.5×109/L；c.PLT≥50×109/L；
- •Biochemical examination: (ALB was not transfused within 14 days before screening) a.ALB ≥29 g/L； b.ALT 和 AST<5ULN；c.TBIL ≤3ULN；d.creatinine ≤1.5ULN( albumin and bilirubin, two indicators of Child-Pugh liver function class, can only have one for 2 points)
- •For women of childbearing age, the results of serum/urine pregnancy tests must be negative within 7 days before initiation of treatment. All men and women who participate in the study have to take reliable contraceptive measures within the trial and eight weeks after the trial is completed
- •volunteers must signed informed consent
排除标准
- •Diffuse hepatocellular carcinoma
- •Vascular invasion, including portal vein tumor thrombus
- •Extra hepatic metastasis
- •Decompensated Cirrhosis: Child-Pugh liver function class B/C(score: >8); jaundice; hepatic encephalopathy; refractory ascites; hepatorenal syndrome
- •With a history of alimentary tract hemorrhage or a definite tendency of gastrointestinal bleeding, such as varices of fundus of stomach and esophagus with bleeding risk; local active ulcer lesions; fecal occult blood ≥（++）
- •Contraindication of embolization: patients with severe hepatic flow or portosystemic shunt; the lesion was too large, and the majority of two lobe were occupied by the lesions
- •Patients whose target lesion has been treated locally: resection of hepatic carcinoma; radio frequency ablation; TACE; local treatment was taken within 4 weeks; patients who have previously been given radiotherapy, chemotherapy, or targeted drugs
- •Patients with hepatobiliary cell carcinoma, mixed cell carcinoma or lamellar cell carcinoma; in the past (within 5 years) or at the same time suffering from other untreated malignant tumors; excluding cured basal cell carcinoma and carcinoma in situs of cervix
- •Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
- •Patients with an allergic history of arginine hydrochloride and trimetazidine hydrochloride
- •The blood pressure can not be reduced to the normal range by the antihypertensive drug treatment in patients with hypertension(systolic pressure>140 mmHg, diastolic pressure>90 mmHg)
- •Patients with myocardial ischemia or myocardial infarction over grade II or a poorly controlled arrhythmia (including QTc interval: men ≥ 450 ms; women ≥ 470 ms)
- •Cardiac functional insufficiency of grade III to IV according to NYHA standard; echocardiography: LVEF<50%
- •Many factors that influence oral medication, such as unable to swallow; chronic diarrhea; intestinal obstruction; the situations which significantly affect the use and absorption of drugs
- •Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before participating the study
- •Dysfunction of blood coagulation(INR>2.0 or PT> 16s，APTT > 43s、TT > 21s，Fbg < 2g/L), having a tendency to bleed or undergoing thrombolysis or anticoagulant therapy; ascites with clinical symptoms, that is requiring therapeutic abdominal paracentesis or drainage or Child-Pugh score ≥2
- •Objective evidence of pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug associated pneumonia, and severe lung function impairment in the past and at present
- •Urine routine showed that urine protein ≥++ or the urine protein in 24 hours>1.0 g
- •Patients who have been treated with potent CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, telithromycin, troleandomycin, erythromycin, cimetidine and so on) within 28 days before participating the study, or potent CYP3A4 inducers (dexamethasone, phenytoin, rifampin, rifabutin, carbamazepine, phenobarbitone and so on) within 12 days before participating the study
- •Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives
- •Patients with mental sickness or the history of psychotropic drug abuse
- •Patients with severe infection (unable to control the infection effectively)
- •The treatment history affecting this program or its efficacy, such as stem cell transplantation, immune regulation (including PD-1 and other test regimens) recently (within half a year)
- •The researchers believe that any other factors unsuitable for entering into the study.
研究组 & 干预措施
One-drug Regimes
Basic drugs therapy of HCC by TACE.
干预措施: Basic drugs therapy of HCC by TACE (Device)
Two-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride
干预措施: Basic drugs therapy of HCC by TACE (Device)
Two-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride
干预措施: Arginine hydrochloride (Drug)
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
干预措施: Basic drugs therapy of HCC by TACE (Device)
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
干预措施: Arginine hydrochloride (Drug)
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
干预措施: Trimetazidine hydrochloride (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: 24 months
Time from start of treatment until the first documented event of symptomatic progression or death.
次要结局
- large vascular invasion or extrahepatic metastasis (MVI/EHV)(24 months)
- Disease Control Rate (DCR)(28 days)
- Overall Survival(36 months)
- Objective Response Rate(ORR)(28 days)
- quality of life(approximately 36 months)
- biomarker(approximately 24 months)
研究者
Zujiang YU
The director of infectious diseases department
The First Affiliated Hospital of Zhengzhou University