HCCPhase 3TIHCCNCT03274427
Treatment of Intermediate-stage Hepatocellular Carcinoma
A Phase 3 study testing Basic drugs therapy of HCC by TACE, 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 transarterial chemoembolization (TACE) combined with arginine hydrochloride and 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 by TACE, Arginine hydrochloride and Trimetazidine hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- 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 primary liver cancer
- 3. 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
- 4. There are CT or MRI measurable lesions
- 5. No major vascular invasion or extra hepatic metastasis
- 6. Child-Pugh liver function class A/B(score: ≤7)
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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. Diffuse hepatocellular carcinoma
- 2. Vascular invasion, including portal vein tumor thrombus
- 3. Extra hepatic metastasis
- 4. Decompensated Cirrhosis: Child-Pugh liver function class B/C(score: >8); jaundice; hepatic encephalopathy; refractory ascites; hepatorenal syndrome
- 5. 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 ≥（++）
- 6. 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
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- 7. 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
- 8. 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
- 9. Patients who are undergoing liver transplantation or have a history of organ transplantation(excluding the patient who has undergone liver transplantation before)
- 10. Patients with an allergic history of arginine hydrochloride and trimetazidine hydrochloride
- 11. 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)
- 12. Patients with myocardial ischemia or myocardial infarction over grade II or a poorly controlled arrhythmia (including QTc interval: men ≥ 450 ms; women ≥ 470 ms)
- 13. Cardiac functional insufficiency of grade III to IV according to NYHA standard; echocardiography: LVEF<50%
- 14. 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
- 15. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before participating the study
- 16. 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
- 17. 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
- 18. Urine routine showed that urine protein ≥++ or the urine protein in 24 hours>1.0 g
- 19. 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
- 20. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives
- 21. Patients with mental sickness or the history of psychotropic drug abuse
- 22. Patients with severe infection (unable to control the infection effectively)
- 23. 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)
- 24. 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 TACE Combined With Arginine Hydrochloride and Trimetazidine Hydrochloride Tablets in With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
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.
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. 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.
- Conditions
- HCC
- Being tested
- Basic drugs therapy of HCC by TACE, 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 HCC by TACEDevice
Also called TACE
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, 20mg/tablet, 40mg, twice a day.
| Study group | Role | What they receive |
|---|---|---|
| One-drug Regimes | Experimental | Basic drugs therapy of HCC by TACE. Receives: Device: Basic drugs therapy of HCC by TACE |
| Two-Drug Regimens | Experimental | Basic drugs therapy of HCC by TACE; Arginine hydrochloride Receives: 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 Receives: Device: Basic drugs therapy of HCC by TACE; Drug: Arginine hydrochloride; Drug: Trimetazidine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Time from start of treatment until the first documented event of symptomatic progression or death.
Measured: 24 months
Secondary outcomes (6)
Overall Survival
from start of treatment to death from any cause, or last known date of survival
Measured: 36 months
large vascular invasion or extrahepatic metastasis (MVI/EHV)
The effect on large vascular invasion or extrahepatic metastasis (MVI/EHV)
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
quality of life
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 posted7 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, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Shenma Medical Group General Hospital, First People's Hospital of Shangqiu, Third People's Hospital of Jiaozuo
- Responsible party
- Principal investigator, Zujiang YU, The First Affiliated Hospital of Zhengzhou University
- Investigators
- Zujiang Yu, Principal investigator, The First Affiliated Hospital of Zhengzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03274427
- Sponsor's protocol ID
- HETCT-002
- Acronym
- TIHCC
- Status last verified
- Sep 2017
- First submitted
- 27 Aug 2017
- Last updated
- 15 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 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of TACE Combined With Arginine Hydrochloride and Trimetazidine Hydrochloride Tablets in With Hepatocellular Carcinoma. A Multicenter, Open, Randomized, Prospective Study
- ClinicalTrials.gov ID
- NCT03274427
- Acronym / sponsor ID
- TIHCC / HETCT-002
- 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, Luoyang Central Hospital, Nanyang Central Hospital, Anyang Tumor Hospital, Shenma Medical Group General Hospital, First People's Hospital of Shangqiu, Third People's Hospital of Jiaozuo
- Study start
- 18 Jul 2017 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Jul 2021 (estimated)
- First posted
- 7 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 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.
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 | Device: Basic drugs therapy of HCC by TACEBasic drugs therapy of HCC by TACE. |
| Two-Drug Regimens | Experimental | Device: Basic drugs therapy of HCC by TACE, Drug: Arginine hydrochlorideBasic drugs therapy of HCC by TACE; Arginine hydrochloride |
| Three-Drug Regimens | Experimental | Device: Basic drugs therapy of HCC by TACE, Drug: Arginine hydrochloride, Drug: Trimetazidine hydrochlorideBasic drugs therapy of HCC by TACE; 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 primary liver cancer
- 3. 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
- 4. There are CT or MRI measurable lesions
- 5. No major vascular invasion or extra hepatic metastasis
Key exclusion criteria (24 listed)
- 1. Diffuse hepatocellular carcinoma
- 2. Vascular invasion, including portal vein tumor thrombus
- 3. Extra hepatic metastasis
- 4. Decompensated Cirrhosis: Child-Pugh liver function class B/C(score: >8); jaundice; hepatic encephalopathy; refractory ascites; hepatorenal syndrome
- 5. 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 ≥（++）
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 HCC by TACEAlso: TACEBasic 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. | Device | 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, 20mg/tablet, 40mg, twice a day. | Drug | Three-Drug Regimens |
Primary outcome
Progression-free Survival
Time frame: 24 months
Time from start of treatment until the first documented event of symptomatic progression or death.
6 secondary outcomes
Overall Survival
Time frame: 36 months
large vascular invasion or extrahepatic metastasis (MVI/EHV)
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
quality of life
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 15 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 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 by TACE, 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 24 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 15 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?
Progression-free Survival (time frame: 24 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 15 Sep 2017.