HCCPhase 3TAHCCNCT03278444
Treatment of Advanced Hepatocellular Carcinoma
A Phase 3 study testing Basic drugs therapy of HCC, Arginine hydrochloride and Trimetazidine hydrochloride in people with HCC, run by The First Affiliated Hospital of Zhengzhou University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HCC
- What is being tested?
- Basic drugs therapy of HCC, Arginine hydrochloride and Trimetazidine hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 18 Jul 2017to Jul 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Ages 18-65 years
- 2. 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
- 3. 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
- 4. 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）
- 5. Child-Pugh liver function class A/B (score: ≤ 9)
- 6. Barcelona stage (BCLC) B-C
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- 7. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale in one week before admission
- 8. Estimated survival time > 3 months
- 9. HBV DNA<2000 IU/ml（10^4 copies/ml); or HBV DNA≥2000 IU/ml and are accepting effective antiviral therapy
- 10. 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)
- 11. 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
- 12. volunteers must signed informed consent
Who cannot join
- 1. 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
- 2. Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
- 3. Patients with an allergic history of arginine hydrochloride and trimetazidine hydrochloride
- 4. Patients with renal insufficiency
- 5. 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)
- 6. Patients with myocardial ischemia or myocardial infarction over grade II or a poorly controlled arrhythmia (including QTc interval: men ≥ 450 ms; women ≥ 470 ms)
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- 7. Cardiac functional insufficiency of grade III to IV according to NYHA standard; echocardiography: LVEF<50%
- 8. 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
- 9. 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 ≥（++）
- 10. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before participating the study
- 11. 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
- 12. Patients of central nervous system metastasis or brain metastasis
- 13. 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
- 14. Urine routine showed that urine protein ≥++ or the urine protein in 24 hours>1.0 g
- 15. 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
- 16. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives
- 17. Patients with mental sickness or the history of psychotropic drug abuse
- 18. Patients who had bone metastases received palliative radiotherapy within 4 weeks before participating the study (radiotherapy area > 5% bone marrow region)
- 19. Patients with severe infection (unable to control the infection effectively)
- 20. 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)
- 21. The researchers believe that any other factors unsuitable for entering into the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450000
About this study
Official title: The Efficacy and Safety of Arginine Hydrochloride Combined With Trimetazidine Hydrochloride Tablets in the Treatment of Patients With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
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.
Read the 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. 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 arginine hydrochloride combined with trimetazidine hydrochloride tablets in the treatment of patients with hepatocellular carcinoma.
- Conditions
- HCC
- Being tested
- Basic drugs therapy of HCC, Arginine hydrochloride, Trimetazidine hydrochloride
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Basic drugs therapy of HCCOther
Also called BDT
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.
Arginine hydrochlorideDrug
Also called AH
Arginine hydrochloride injection 5g/dose; 40g/d; ivgtt; sustained medication for 24 days; drug withdrawal for 4 days.
Trimetazidine hydrochlorideDrug
Also called TH
Trimetazidine hydrochloride tablets 20mg/tablet, 40mg, twice a day.
| Study group | Role | What they receive |
|---|---|---|
| One-drug Regimes | Experimental | Basic drugs therapy of HCC Receives: Other: Basic drugs therapy of HCC |
| Two-Drug Regimens | Experimental | Basic drugs therapy of HCC; Arginine hydrochloride Receives: Other: Basic drugs therapy of HCC; Drug: Arginine hydrochloride |
| Three-Drug Regimens | Experimental | Basic drugs therapy of HCC; Arginine hydrochloride;Trimetazidine hydrochloride Receives: Other: Basic drugs therapy of HCC; Drug: Arginine hydrochloride; Drug: Trimetazidine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
from start of treatment to death from any cause, or last known date of survival
Measured: 36 months
Secondary outcomes (5)
Progression-free Survival
Time from start of treatment until the first documented event of symptomatic progression or death.
Measured: 24 months
Disease Control Rate (DCR)
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease
Measured: 28 days
Objective Response Rate(ORR)
Proportion of patients with reduction in tumor burden of a predefined amount
Measured: 28 days
biomarker
decrease in tumor markers
Measured: approximately 24 months
Chinese Quality of Life Questionnaire - EORTC QLQ-C30 score
The overall enjoyment of life.
Measured: approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start18 Jul 2017
- Primary completionJul 2021 (estimated)
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCCStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Zhengzhou UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- First Affiliated Hospital of Xinjiang Medical University, Third People's Hospital of Jiaozuo, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Pingmei Shenma Medical Group General Hospital, First People's Hospital of Shangqiu
- Responsible party
- Principal investigator, Zujiang YU, The First Affiliated Hospital of Zhengzhou University
- Investigators
- Zujiang Yu, Pro,Dr, Principal investigator, The First Affiliated Hospital of Zhengzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03278444
- Sponsor's protocol ID
- HETCT-001
- Acronym
- TAHCC
- Status last verified
- Sep 2017
- First submitted
- 27 Aug 2017
- Last updated
- 12 Sep 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Arginine Hydrochloride Combined With Trimetazidine Hydrochloride Tablets in the Treatment of Patients With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
- ClinicalTrials.gov ID
- NCT03278444
- Acronym / sponsor ID
- TAHCC / HETCT-001
- Conditions
- HCC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Zhengzhou UniversityUniversity, hospital or other
- Collaborators
- First Affiliated Hospital of Xinjiang Medical University, Third People's Hospital of Jiaozuo, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Pingmei Shenma Medical Group General Hospital, First People's Hospital of Shangqiu
- Study start
- 18 Jul 2017 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Jul 2021 (estimated)
- First posted
- 11 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. 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 arginine hydrochloride combined with trimetazidine hydrochloride tablets in the treatment of patients with hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| One-drug Regimes | Experimental | Other: Basic drugs therapy of HCCBasic drugs therapy of HCC |
| Two-Drug Regimens | Experimental | Other: Basic drugs therapy of HCC, Drug: Arginine hydrochlorideBasic drugs therapy of HCC; Arginine hydrochloride |
| Three-Drug Regimens | Experimental | Other: Basic drugs therapy of HCC, Drug: Arginine hydrochloride, Drug: Trimetazidine hydrochlorideBasic drugs therapy of HCC; Arginine hydrochloride;Trimetazidine hydrochloride |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 1. Ages 18-65 years
- 2. 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
- 3. 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
- 4. 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）
- 5. Child-Pugh liver function class A/B (score: ≤ 9)
Key exclusion criteria (21 listed)
- 1. 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
- 2. Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
- 3. Patients with an allergic history of arginine hydrochloride and trimetazidine hydrochloride
- 4. Patients with renal insufficiency
- 5. 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Basic drugs therapy of HCCAlso: BDTBasic 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. | Other | One-drug Regimes, Three-Drug Regimens, Two-Drug Regimens |
| Arginine hydrochlorideAlso: AHArginine hydrochloride injection 5g/dose; 40g/d; ivgtt; sustained medication for 24 days; drug withdrawal for 4 days. | Drug | Three-Drug Regimens, Two-Drug Regimens |
| Trimetazidine hydrochlorideAlso: THTrimetazidine hydrochloride tablets 20mg/tablet, 40mg, twice a day. | Drug | Three-Drug Regimens |
Primary outcome
Overall Survival
Time frame: 36 months
from start of treatment to death from any cause, or last known date of survival
5 secondary outcomes
Progression-free Survival
Time frame: 24 months
Disease Control Rate (DCR)
Time frame: 28 days
Objective Response Rate(ORR)
Time frame: 28 days
biomarker
Time frame: approximately 24 months
Chinese Quality of Life Questionnaire - EORTC QLQ-C30 score
Time frame: approximately 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zujiang Yu, Pro,Dr principal investigator
The First Affiliated Hospital of Zhengzhou University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Basic drugs therapy of HCC, Arginine hydrochloride and Trimetazidine hydrochloride in people with HCC, run by The First Affiliated Hospital of Zhengzhou University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zujiang Yu, Pro,Dr (0086-0371-67966942, johnyuem@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2017; AzTrials last refreshed its copy on 7 Nov 2026.