A Study of CD147-targeted CAR-T by Hepatic Artery Infusions for Very Advanced Hepatocellular Carcinoma

August 24, 2019 updated by: Chen Zhinan, Xijing Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710032
        • Recruiting
        • Department of hepato-biliary & Pancreato Splenic Surgery Organ Transplant Center, Xijing Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 18 year and ≤ 65 years, both male and female.
  2. 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.
  3. The portal vein is not total occlusion, or collateral circulation has formed between hepatic artery and blocked portal vein.
  4. Patient with measurable HCC focus defined by mRECIST.
  5. Patient with histologically confirmed diagnosis of CD147+ hepatocellular carcinoma.
  6. Adequate venous access for apheresis, and no other contraindications for apheresis.
  7. Child-Pugh score ≤7.
  8. Eastern Cooperative Oncology Group(ECOG) performance status of 0-2.
  9. Patient with a life expectancy of greater than three months.
  10. Patients must able to understand and be willing to sign an informed consent.

Exclusion Criteria:

  1. Patients with fibrolamellar carcinoma of liver，mixed hepatocellular carcinoma or cholangiocarcinoma.
  2. Patients with severe hypohepatia including jaundice, hepatic encephalopathy, refractory ascites or hepatorenal syndrome.

  3. Patients with severe comorbidity, including any of the following.

    1. Unstable angina pectoris and/or congestive heart failure need hospitalization;
    2. Myocardial infarction or cerebrovascular accident (CVA) in the last 6 months;
    3. chronic obstructive pulmonary disease progressions or need hospitalization;
    4. severe cardiovascular, nervous system, hematological, gastrointestinal, endocrine diseases or metabolic disorders;
    5. autoimmune disease or immunodeficiency disease;
    6. acute bacterial infections or fungal infections needs intravenous injection of antibiotics during CAR-T cell therapy;
    7. tuberculosis not cured;
    8. other malignancies;
  4. Patients who have received gene therapy, cell therapy or immune therapy.
  5. Patients who have received organ transplantation.
  6. Patients who have received treatment of targeted drugs, glucocorticoid or immunosuppressive drugs within 2 weeks before enrolling in clinical trial.
  7. Patients who have received chemotherapy except for lymphocyte clearance within 2 weeks before enrolling in clinical trial.
  8. Patients who have received radiotherapy.
  9. 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.
  10. 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.

  11. Patients with following abnormalities:

    1. Absolute neutrophil count (ANC) < 1.5E9/L, platelet(PLT) < 50E9/L, or hemoglobin(HGB)< 80 g/dL;
    2. Prothrombin time (PT), activated partial thromboplastin time (APTT) or international normalized ratio (INR) > 1.5×ULN (upper normal value);
    3. Total bilirubin(TBIL) > 2×ULN; ALT, AST or ALP>5×ULN;
    4. Serum creatinine (Cr)≥1.5×ULN or glomerular filtration rate (GFR) < 60 mL/min·1.73m^2;
    5. left ventricular ejection fraction (LVEF) < 50%;
  12. Patients with a history of allergic reactions attributed to any agents or compounds involved in this study.
  13. Patients with a history of mental disorders.
  14. Patients with a history of drug abuse.
  15. Pregnant and lactating women.
  16. Patients of childbearing age who unwilling or unable to take birth control from during this study and 3 months post this study.
  17. Patients who receive any other investigational agents within the 3 months before enrolling in this clinical trial.
  18. Investigator considers not suitable for this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: CD147-CART
Infusions of CD147-CART cells over the course of each week for 3 times into the hepatic artery
Biological: CD147-CART
Three infusions of CD147-CART cells over the course of three weeks into the hepatic artery.
Other Names:
  • anti-CD147 chimeric antigen receptor T cell

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
DLT and MTD of CD147-CART cell hepatic artery infusions
Time Frame: 12 weeks
To determine the dose limited toxicity (DLT) and maximum tolerated dose (MTD) of CD147-CART hepatic artery infusions.
12 weeks
Activity of CD147-CART cell hepatic artery infusions
Time Frame: 2 years
To evaluate treatment response of CD147-CART hepatic artery infusions for very advanced hepatocellular carcinoma.
2 years
CD147-CART detection in extrahepatic sites
Time Frame: 2 years
Quantification of CD147-CART cells in blood samples.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xijing Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 27, 2019

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 27, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 27, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 19, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Chen Zhinan-1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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