Treatment of Advanced Hepatocellular Carcinoma

NCT03278444 | Unknown Phase 3

• 1 other identifier: HETCT-001
• 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 arginine hydrochloride combined with trimetazidine hydrochloride tablets in the treatment of patients with hepatocellular carcinoma.

Conditions

HCC

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  from start of treatment to death from any cause, or last known date of survival

  36 months

Secondary Outcomes (5)

• Progression-free Survival

  24 months

• Disease Control Rate (DCR)

  28 days

• Objective Response Rate(ORR)

  28 days

• biomarker

  approximately 24 months

• Chinese Quality of Life Questionnaire - EORTC QLQ-C30 score

  approximately 36 months

Study Arms (3)

One-drug Regimes

EXPERIMENTAL

Basic drugs therapy of HCC

Other: Basic drugs therapy of HCC

Two-Drug Regimens

EXPERIMENTAL

Basic drugs therapy of HCC; Arginine hydrochloride

Other: Basic drugs therapy of HCC; Drug: Arginine hydrochloride

Three-Drug Regimens

EXPERIMENTAL

Basic drugs therapy of HCC; Arginine hydrochloride;Trimetazidine hydrochloride

Other: Basic drugs therapy of HCC; Drug: Arginine hydrochloride; Drug: Trimetazidine hydrochloride

Interventions

Basic drugs therapy of HCC OTHER

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: BDT

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 tablets 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 recurrent / metastatic primary liver cancer
• \. Un-resectable HCC (single or multiple metastasis of HCC after surgery, TACE, or radio frequency ablation; surgery cannot be tolerated because of some basic diseases); Patients with treatment failure or non tolerance to sorafenib. ｛note: Definition of treatment failure: progression of disease during treatment or recurrence of disease after the end of treatment(accepting sorafenib and other molecular targeted therapies must be at least 14 days); Definition of intolerance: ≥ grade Ⅳ hematological toxicity or ≥ grade III non hematologic toxicity or ≥ grade Ⅱ heart, liver, kidney and other organ damage｝;Refusing surgical treatment and volunteering join the group
• \. first-line systematic treatment failure (or residual lesion) was over 2 weeks from the study enrolled (time for signature of informed consent) and the adverse events were almost normal (NCI-CTCAE≤ grade Ⅰ）
• \. Child-Pugh liver function class A/B (score: ≤ 9)
• \. Barcelona stage (BCLC) B-C
• \. 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:

• \. 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
• \. Patients with renal insufficiency
• \. 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
• \. 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 ≥（++）
• \. 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
• \. Patients of central nervous system metastasis or brain metastasis
• \. 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

Sponsors & Collaborators

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

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

RECRUITING

MeSH Terms

Interventions

N-((2,3-dihydro-1,4-benzodioxin-2-yl)methyl)-5-methoxy-1H-indole-3-ethanamine; 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, Pro,Dr

  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 11, 2017
• Study Start: July 18, 2017
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: September 12, 2017

Record last verified: 2017-09

Locations

CN (1)