The Efficacy and Safety of TACE Combined With Arginine Hydrochloride and Trimetazidine Hydrochloride Tablets in With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
Overview
- Phase
- Phase 3
- Intervention
- Basic drugs therapy of HCC by TACE
- Conditions
- HCC
- Sponsor
- The First Affiliated Hospital of Zhengzhou University
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Progression-free Survival
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Zujiang YU
The director of infectious diseases department
The First Affiliated Hospital of Zhengzhou University
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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
Arms & Interventions
One-drug Regimes
Basic drugs therapy of HCC by TACE.
Intervention: Basic drugs therapy of HCC by TACE
Two-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride
Intervention: Basic drugs therapy of HCC by TACE
Two-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride
Intervention: Arginine hydrochloride
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
Intervention: Basic drugs therapy of HCC by TACE
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
Intervention: Arginine hydrochloride
Three-Drug Regimens
Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride
Intervention: Trimetazidine hydrochloride
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: 24 months
Time from start of treatment until the first documented event of symptomatic progression or death.
Secondary Outcomes
- 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)