Treatment of Intermediate-stage Hepatocellular Carcinoma

NCT03274427 | Unknown Phase 3

• 1 other identifier: HETCT-002
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

HCC

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Time from start of treatment until the first documented event of symptomatic progression or death.

  24 months

Secondary Outcomes (6)

• Overall Survival

  36 months

• large vascular invasion or extrahepatic metastasis (MVI/EHV)

  24 months

• Disease Control Rate (DCR)

  28 days

• Objective Response Rate(ORR)

  28 days

• biomarker

  approximately 24 months

Study Arms (3)

One-drug Regimes

EXPERIMENTAL

Basic drugs therapy of HCC by TACE.

Device: Basic drugs therapy of HCC by TACE

Two-Drug Regimens

EXPERIMENTAL

Basic drugs therapy of HCC by TACE; Arginine hydrochloride

Device: Basic drugs therapy of HCC by TACE; Drug: Arginine hydrochloride

Three-Drug Regimens

EXPERIMENTAL

Basic drugs therapy of HCC by TACE; Arginine hydrochloride;Trimetazidine hydrochloride

Device: Basic drugs therapy of HCC by TACE; Drug: Arginine hydrochloride; Drug: Trimetazidine hydrochloride

Interventions

Basic drugs therapy of HCC by TACE DEVICE

Basic drugs include: 1. Molecular targeted drugs for HCC：apatinib; 2. Antiviral drugs (ETV or TDF) should be given to patients who were infected with HBV or HCV; 3. Patients with liver dysfunction should be treated with conventional hepatoprotective agents drugs (including glycyrrhizin, reduced glutathione, vitamin C，etc); 4. Patients with ascites symptoms should be treated with furosemide and spironolactone according to the urine volume, and they also should be treated with proton pump inhibitors in the prevention of gastrointestinal bleeding; 5. Other basic diseases were treated routinely.

Also known as: TACE

One-drug Regimes; Three-Drug Regimens; Two-Drug Regimens

Arginine hydrochloride DRUG

Arginine hydrochloride injection 5g/dose; 40g/d; ivgtt; sustained medication for 24 days; drug withdrawal for 4 days.

Also known as: AH

Three-Drug Regimens; Two-Drug Regimens

Trimetazidine hydrochloride DRUG

Trimetazidine hydrochloride, 20mg/tablet, 40mg, twice a day.

Also known as: TH

Three-Drug Regimens

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead
• First Affiliated Hospital of Xinjiang Medical University: collaborator
• Luoyang Central Hospital: collaborator
• Nanyang Central Hospital: collaborator
• Anyang Tumor Hospital: collaborator
• Shenma Medical Group General Hospital: collaborator
• First People's Hospital of Shangqiu: collaborator
• Jiaozuo third people's hospital: collaborator

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

RECRUITING

MeSH Terms

Interventions

Arginine; Trimetazidine

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zujiang Yu

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zujiang Yu, Pro,Dr

CONTACT

0086-0371-67966942; johnyuem@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The director of infectious diseases department

Study Record Dates

• First Submitted: August 27, 2017
• First Posted: September 7, 2017
• Study Start: July 18, 2017
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: September 15, 2017

Record last verified: 2017-09

Locations

CN (1)