Carcinoma, HepatocellularPhase 1/2GPC3-CARTNCT02715362
A Study of GPC3 Redirected Autologous T Cells for Advanced HCC
A Phase 1/2 study testing TAI-GPC3-CART cells in people with Carcinoma, Hepatocellular, run by Shanghai GeneChem Co., Ltd. at 1 site in China.
Trial summary
Intravenous infusion of CART cells in the treatment of solid tumors may be not a suitable choice. Because by intravenous infusion, T cells first entered into the blood circulation, but the number of T cells accumulated at the tumor site is limited, while the probability is high that CART cells contact with normal… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- TAI-GPC3-CART cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- Mar 2016to Mar 2019
- Phase
- Phase 1/2
- 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- GPC3 expression positive and histologically confirmed as hepatocellular carcinoma;
- Aged between 18 and 69;
- Persistent cancer after at least one prior standard of care chemotherapy, has no willing for surgery or cannot be suitable for surgery patients;
- Life expectancy greater than 6 months;
- Satisfactory organ and bone marrow function as defined by the following: (1) creatinine <1.5mg/dl; (2) albumin >2; (3) cardiac ejection fraction of >55%; (4) hemoglobin>9g/dl, bilirubin 2.0×the institution normal upper limit;
- Without bleeding disorder or coagulation disorders;
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- Dont allergy to Radiocontrast agent;
- Birth control;
- Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- Voluntary informed consent is given.
Who cannot join
- Pregnant or lactating women;
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary;
- Patients in the situation of: (1) 30 days before apheresis is still in the period of other antitumor drug observation; (2) patient dont recuperate from earlier acute adverse influence brought by any treatments accepted before;
- Four weeks before recruit accepted radiation therapy;
- Previously treatment with any gene therapy products;
- Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation;
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- Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade III or IV cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases, CNS diseases);
- Patient with severe acute hypersensitive reaction;
- Taking part in other clinical trials;
- Study leader considers not suitable for this tiral.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality
Xu Aimin, Doctor, 86-13918183196, xuarmy@163.com
Yu Xuejun, Master, 86-18616108610, yuxuejun@genechem.com.cn
About this study
Official title: An Open-label, Uncontrolled, Single-arm Pilot Study to Evaluate Vascular Interventional Therapy Mediated GPC3-targeted Chimeric Antigen Receptor T Cells in Advanced Hepatocellular Carcinoma
Intravenous infusion of CART cells in the treatment of solid tumors may be not a suitable choice. Because by intravenous infusion, T cells first entered into the blood circulation, but the number of T cells accumulated at the tumor site is limited, while the probability is high that CART cells contact with normal tissue where target protein is expressed, leading to a more potential off-target side effect. In this study, CART cells infused to the body is mediated by the method of transcatheter arterial infusion(TAI), which is one kind of tumor intervention therapy pathway. We hope by this means could improve the local CAR-T cell numbers，meanwhile reduce the potential side effects.
Read the detailed description
Patients treated with leukapheresis from which peripheral blood mononuclear cells are purified. T cells are activated and then re-engineered to express chimeric antigen receptors (CARs) specific for GPC3. Cells are expanded in culture and returned to the participant by transcatheter arterial infusion at the dose of .(1-10)×106 CAR positive T cells/kg. The cells perfusion process would last for 15min to 2 h via an ambulatory infusion pump. A single dose of 1.5 grams/m2 of cyclophosphamide will be given two days before CART cell infusion.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- TAI-GPC3-CART cells
- Keywords
- immunotherapy GPC3 CAR-T HCC
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAI-GPC3-CART cellsDrug
Also called Gene modified patient T cells
TAI as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrated to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And GPC3-CART is a 2nd CAR, with GPC3 as the target protein, 4-1BB as a co- stimulator
| Study group | Role | What they receive |
|---|---|---|
| TAI-GPC3-CART cells | Experimental | A single dose of GPC3-CART cells will be administered by transcatheter arterial infusion(TAI) mediated as one dose infusion. The dose is 1-10x106/kg GPC3-CAR positive T cells. The infusion will be scheduled to occur 2 days after a single dose of 1.5 grams/m2 of cyclophosphamide. Patients will undergo cannula--DSA radiography--CAR-T cells perfused into hepatic artery. The cells perfusion process would last 15min to 2 h, and the specific time depends on patent's tumor-burdened state. Receives: Drug: TAI-GPC3-CART cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events
To determine the safety and regimen limiting toxicity (RLT) of anti-GPC3 CAR-T transcatheter arterial infusion (TAI) for GPC3-expressing HCC.
Measured: 6 weeks
Secondary outcomes (3)
Number of participants with tumor response as measured by RECIST
Measured: 8 weeks
Detection of CART cells in the circulation using quantitative -PCR
Measured: 8 weeks
Serum cytokine levels
Measurement of cytokines as indicators of immune response, including IL-2/IL-6/IL-10/TNF/IL-2R
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionJul 2018 (estimated)
- Study completionMar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai GeneChem Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xu Aimin, Doctor, Principal investigator, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02715362
- Sponsor's protocol ID
- GeneChem GPC3-CART
- Acronym
- GPC3-CART
- Status last verified
- Mar 2016
- First submitted
- 11 Mar 2016
- Last updated
- 22 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Uncontrolled, Single-arm Pilot Study to Evaluate Vascular Interventional Therapy Mediated GPC3-targeted Chimeric Antigen Receptor T Cells in Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT02715362
- Acronym / sponsor ID
- GPC3-CART / GeneChem GPC3-CART
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- immunotherapy GPC3 CAR-T HCC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Shanghai GeneChem Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 22 Mar 2016 (estimated)
- 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.
Intravenous infusion of CART cells in the treatment of solid tumors may be not a suitable choice. Because by intravenous infusion, T cells first entered into the blood circulation, but the number of T cells accumulated at the tumor site is limited, while the probability is high that CART cells contact with normal tissue where target protein is expressed, leading to a more potential off-target side effect. In this study, CART cells infused to the body is mediated by the method of transcatheter arterial infusion(TAI), which is one kind of tumor intervention therapy pathway. We hope by this means could improve the local CAR-T cell numbers，meanwhile reduce the potential side effects.
Detailed description
Patients treated with leukapheresis from which peripheral blood mononuclear cells are purified. T cells are activated and then re-engineered to express chimeric antigen receptors (CARs) specific for GPC3. Cells are expanded in culture and returned to the participant by transcatheter arterial infusion at the dose of .(1-10)×106 CAR positive T cells/kg. The cells perfusion process would last for 15min to 2 h via an ambulatory infusion pump. A single dose of 1.5 grams/m2 of cyclophosphamide will be given two days before CART cell infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAI-GPC3-CART cells | Experimental | Drug: TAI-GPC3-CART cellsA single dose of GPC3-CART cells will be administered by transcatheter arterial infusion(TAI) mediated as one dose infusion. The dose is 1-10x106/kg GPC3-CAR positive T cells. The infusion will be scheduled to occur 2 days after a single dose of 1.5 grams/m2 of cyclophosphamide. Patients will undergo cannula--DSA radiography--CAR-T cells perfused into hepatic artery. The cells perfusion process would last 15min to 2 h, and the specific time depends on patent's tumor-burdened state. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- GPC3 expression positive and histologically confirmed as hepatocellular carcinoma;
- Aged between 18 and 69;
- Persistent cancer after at least one prior standard of care chemotherapy, has no willing for surgery or cannot be suitable for surgery patients;
- Life expectancy greater than 6 months;
- Satisfactory organ and bone marrow function as defined by the following: (1) creatinine <1.5mg/dl; (2) albumin >2; (3) cardiac ejection fraction of >55%; (4) hemoglobin>9g/dl, bilirubin 2.0×the institution normal upper limit;
Key exclusion criteria (10 listed)
- Pregnant or lactating women;
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary;
- Patients in the situation of: (1) 30 days before apheresis is still in the period of other antitumor drug observation; (2) patient dont recuperate from earlier acute adverse influence brought by any treatments accepted before;
- Four weeks before recruit accepted radiation therapy;
- Previously treatment with any gene therapy products;
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 |
|---|---|---|
| TAI-GPC3-CART cellsAlso: Gene modified patient T cellsTAI as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrated to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And GPC3-CART is a 2nd CAR, with GPC3 as the target protein, 4-1BB as a co- stimulator | Drug | TAI-GPC3-CART cells |
Primary outcome
Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events
Time frame: 6 weeks
To determine the safety and regimen limiting toxicity (RLT) of anti-GPC3 CAR-T transcatheter arterial infusion (TAI) for GPC3-expressing HCC.
3 secondary outcomes
Number of participants with tumor response as measured by RECIST
Time frame: 8 weeks
Detection of CART cells in the circulation using quantitative -PCR
Time frame: 8 weeks
Serum cytokine levels
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2016.
- Individual participant dataSharing planned: Undecided
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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.
Xu Aimin, Doctor principal investigator
RenJi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TAI-GPC3-CART cells in people with Carcinoma, Hepatocellular, run by Shanghai GeneChem Co., Ltd. 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 10 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 22 Mar 2016. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Xu Aimin, Doctor (+86 13918183196, xuarmy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of CAR-T cell infusion mediated by TAI as measured by number of participants with adverse Events (time frame: 6 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 22 Mar 2016.