Advanced Hepatocellular CarcinomaPhase 1NCT03993743
A Study of CD147-targeted CAR-T by Hepatic Artery Infusions for Very Advanced Hepatocellular Carcinoma
A Phase 1 study testing CD147-CART in people with Advanced Hepatocellular Carcinoma, run by Xijing Hospital at 1 site in China.
Trial summary
This is a single-center, single-arm, open label and dose escalation clinical study of anti-CD147 CART cells by hepatic artery infusions in patients with advanced hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- CD147-CART
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteChina
- Study dates
- 27 May 2019to 27 May 2022
- Phase
- Phase 1
- 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
- Age ≥ 18 year and ≤ 65 years, both male and female.
- Advanced hepatocellular carcinoma(HCC) patient, which is untreatable by surgery or local therapy, or has postoperative progressions, failed at least one and two line of standard systemic chemotherapy, and unwilling or intolerance to targeting therapy or immune-therapy of cancer.
- The portal vein is not total occlusion, or collateral circulation has formed between hepatic artery and blocked portal vein.
- Patient with measurable HCC focus defined by mRECIST.
- Patient with histologically confirmed diagnosis of CD147+ hepatocellular carcinoma.
- Adequate venous access for apheresis, and no other contraindications for apheresis.
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- Child-Pugh score ≤7.
- Eastern Cooperative Oncology Group(ECOG) performance status of 0-2.
- Patient with a life expectancy of greater than three months.
- Patients must able to understand and be willing to sign an informed consent.
Who cannot join
- Patients with fibrolamellar carcinoma of liver，mixed hepatocellular carcinoma or cholangiocarcinoma.
- Patients with severe hypohepatia including jaundice, hepatic encephalopathy, refractory ascites or hepatorenal syndrome.
- Patients with severe comorbidity, including any of the following.
- Unstable angina pectoris and/or congestive heart failure need hospitalization;
- Myocardial infarction or cerebrovascular accident (CVA) in the last 6 months;
- chronic obstructive pulmonary disease progressions or need hospitalization;
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- severe cardiovascular, nervous system, hematological, gastrointestinal, endocrine diseases or metabolic disorders;
- autoimmune disease or immunodeficiency disease;
- acute bacterial infections or fungal infections needs intravenous injection of antibiotics during CAR-T cell therapy;
- tuberculosis not cured;
- other malignancies;
- Patients who have received gene therapy, cell therapy or immune therapy.
- Patients who have received organ transplantation.
- Patients who have received treatment of targeted drugs, glucocorticoid or immunosuppressive drugs within 2 weeks before enrolling in clinical trial.
- Patients who have received chemotherapy except for lymphocyte clearance within 2 weeks before enrolling in clinical trial.
- Patients who have received radiotherapy.
- Patients who did not recover to CTCAE(v5.0) grade 1 from adverse events （except hair）of previous anti-tumor therapy before enrolling in trial.
- Syphilis test (TRUST) positive, Anti-HIV positive, Anti-HCV positive with HCV-RNA level higher than the lower limit of detection(LOD), or HBcAb positive with HBV-DNA level higher than the LOD.
- Patients with following abnormalities:
- Absolute neutrophil count (ANC) < 1.5E9/L, platelet(PLT) < 50E9/L, or hemoglobin(HGB)< 80 g/dL;
- Prothrombin time (PT), activated partial thromboplastin time (APTT) or international normalized ratio (INR) > 1.5×ULN (upper normal value);
- Total bilirubin(TBIL) > 2×ULN; ALT, AST or ALP>5×ULN;
- Serum creatinine (Cr)≥1.5×ULN or glomerular filtration rate (GFR) < 60 mL/min·1.73m^2;
- left ventricular ejection fraction (LVEF) < 50%;
- Patients with a history of allergic reactions attributed to any agents or compounds involved in this study.
- Patients with a history of mental disorders.
- Patients with a history of drug abuse.
- Pregnant and lactating women.
- Patients of childbearing age who unwilling or unable to take birth control from during this study and 3 months post this study.
- Patients who receive any other investigational agents within the 3 months before enrolling in this clinical trial.
- Investigator considers not suitable for this trial.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of hepato-biliary & Pancreato Splenic Surgery Organ Transplant Center, Xijing Hospital
Xi'an, Shaanxi, 710032
Kaishan Tao, Dr, taokaishan0686@163.com
About this study
Official title: An Open-label, Dose Escalation Clinical Study to Access the Safety and Clinical Activity of CD147-targeted CART by Hepatic Artery Infusions for Very Advanced Hepatocellular Carcinoma
This is a single-center, single-arm, open label and dose escalation clinical study of anti-CD147 CART cells by hepatic artery infusions in patients with advanced hepatocellular carcinoma.
Read the detailed description
Patients autologous T cells are activated and then engineered to express chimeric antigen receptors (CARs) specific for CD147(CD147-CART). CAR-T cells are expanded in culture and returned to the patient by hepatic artery infusion at specific cell doses. Four CD147-CART doses patient are planned at 1-week intervals. Tumor biopsies will be obtained at the time of the initial diagnostic angiogram and during the first infusion session. Serum cytokine level and CAR-T cell number will be measured in whole treatment session.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- CD147-CART
- Keywords
- liver cancer, CD147, CAR-T
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD147-CARTBiological
Also called anti-CD147 chimeric antigen receptor T cell
Three infusions of CD147-CART cells over the course of three weeks into the hepatic artery.
| Study group | Role | What they receive |
|---|---|---|
| CD147-CART | Experimental | Infusions of CD147-CART cells over the course of each week for 3 times into the hepatic artery Receives: Biological: CD147-CART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and type of adverse events induced by CD147-CART hepatic artery infusions
To assess the safety of CD147-CART (anti-CD147 CAR-T cell) hepatic artery infusions (HAI) for very advanced hepatocellular carcinoma which measured by number and type of adverse events.
Measured: 12 weeks
Secondary outcomes (3)
DLT and MTD of CD147-CART cell hepatic artery infusions
To determine the dose limited toxicity (DLT) and maximum tolerated dose (MTD) of CD147-CART hepatic artery infusions.
Measured: 12 weeks
Activity of CD147-CART cell hepatic artery infusions
To evaluate treatment response of CD147-CART hepatic artery infusions for very advanced hepatocellular carcinoma.
Measured: 2 years
CD147-CART detection in extrahepatic sites
Quantification of CD147-CART cells in blood samples.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start27 May 2019
- Primary completion27 Oct 2020 (estimated)
- Study completion27 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Zhinan, Air Force Military Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03993743
- Sponsor's protocol ID
- Chen Zhinan-1
- Status last verified
- Aug 2019
- First submitted
- 19 Jun 2019
- Last updated
- 28 Aug 2019
- 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 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose Escalation Clinical Study to Access the Safety and Clinical Activity of CD147-targeted CART by Hepatic Artery Infusions for Very Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03993743
- Acronym / sponsor ID
- Chen Zhinan-1
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- liver cancer, CD147, CAR-T
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Study start
- 27 May 2019 (actual)
- Primary completion
- 27 Oct 2020 (estimated)
- Study completion
- 27 May 2022 (estimated)
- First posted
- 21 Jun 2019 (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.
This is a single-center, single-arm, open label and dose escalation clinical study of anti-CD147 CART cells by hepatic artery infusions in patients with advanced hepatocellular carcinoma.
Detailed description
Patients autologous T cells are activated and then engineered to express chimeric antigen receptors (CARs) specific for CD147(CD147-CART). CAR-T cells are expanded in culture and returned to the patient by hepatic artery infusion at specific cell doses. Four CD147-CART doses patient are planned at 1-week intervals. Tumor biopsies will be obtained at the time of the initial diagnostic angiogram and during the first infusion session. Serum cytokine level and CAR-T cell number will be measured in whole treatment session.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD147-CART | Experimental | Biological: CD147-CARTInfusions of CD147-CART cells over the course of each week for 3 times into the hepatic artery |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 year and ≤ 65 years, both male and female.
- Advanced hepatocellular carcinoma(HCC) patient, which is untreatable by surgery or local therapy, or has postoperative progressions, failed at least one and two line of standard systemic chemotherapy, and unwilling or intolerance to targeting therapy or immune-therapy of cancer.
- The portal vein is not total occlusion, or collateral circulation has formed between hepatic artery and blocked portal vein.
- Patient with measurable HCC focus defined by mRECIST.
- Patient with histologically confirmed diagnosis of CD147+ hepatocellular carcinoma.
Key exclusion criteria (31 listed)
- Patients with fibrolamellar carcinoma of liver，mixed hepatocellular carcinoma or cholangiocarcinoma.
- Patients with severe hypohepatia including jaundice, hepatic encephalopathy, refractory ascites or hepatorenal syndrome.
- Patients with severe comorbidity, including any of the following.
- Patients who have received gene therapy, cell therapy or immune therapy.
- Patients who have received organ transplantation.
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 |
|---|---|---|
| CD147-CARTAlso: anti-CD147 chimeric antigen receptor T cellThree infusions of CD147-CART cells over the course of three weeks into the hepatic artery. | Biological | CD147-CART |
Primary outcome
Incidence and type of adverse events induced by CD147-CART hepatic artery infusions
Time frame: 12 weeks
To assess the safety of CD147-CART (anti-CD147 CAR-T cell) hepatic artery infusions (HAI) for very advanced hepatocellular carcinoma which measured by number and type of adverse events.
3 secondary outcomes
DLT and MTD of CD147-CART cell hepatic artery infusions
Time frame: 12 weeks
Activity of CD147-CART cell hepatic artery infusions
Time frame: 2 years
CD147-CART detection in extrahepatic sites
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD147-CART in people with Advanced Hepatocellular Carcinoma, run by Xijing Hospital 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 10 inclusion and 31 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 28 Aug 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Zhi-Nan Chen, PhD (86-029-84774547, znchen@fmmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and type of adverse events induced by CD147-CART hepatic artery infusions (time frame: 12 weeks). 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 28 Aug 2019.