Gastric CancerEarly Phase 1NCT06224738
Human HER2-targeted Macrophages Therapy for HER2-positive Advanced Gastric Cancer With Peritoneal Metastases
A Early Phase 1 study testing human HER2-targeted CAR-M cells in people with Gastric Cancer, run by First People's Hospital of Hangzhou at 1 site in China.
Trial summary
The goal of this exploratory clinical trial is to evaluate the safety and efficacy of human anti-human epidermal growth factor receptor 2(HER2) Chimeric antigen receptor macrophage cells (CAR-M) in advanced HER2+ gastric cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastric Cancer
- What is being tested?
- human HER2-targeted CAR-M cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2024to 1 Mar 2026
- Phase
- Early 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age between 18 and 75 years (including borderline values), male or female.
- expected survival of more than 12 weeks.
- histologically confirmed HER2-positive gastric cancer; HER2-positive is defined as immunohistochemistry (IHC) 3+ or (IHC) 2+ with in situ hybridization (ISH) +.
- confirmation of peritoneal metastasis by imaging or cytologic testing of peritoneal fluid.
- presence of measurable lesions.
- patients with peritoneal metastases of gastric cancer who had previously failed second-line or higher therapy. Treatment failure is defined as an intolerable toxic reaction or disease progression during treatment or tumor recurrence or metastasis after completion of treatment. Prior therapy of targeted agents, immunosuppressants, or radiotherapy is permitted; prior systemic therapy with at least 1-2 chemotherapeutic agents of fluorouracil, platinum, and paclitaxel in combination with targeted agents.
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- have an Eastern Cooperative Oncology Group (ECOG) activity status score of 0-2
- at least 2 weeks have elapsed since receiving the most recent drug therapy to the time of single nucleated cell collection.
- patients of childbearing age are required to use appropriate contraception (protection or other birth control) prior to enrollment and during the study.
- the patient is willing to accept intraperitoneal administration of the drug.
- the patient understands the trial and has signed an informed consent form.
- the patient is able to follow the study protocol and follow-up procedures.
Who cannot join
- previous or current other types of malignant tumors, except for the following: completely resected or eradicated basal and squamous cell carcinoma of the skin, and carcinoma in situ of the cervix.
- patients requiring immunosuppressive drugs (except physiologic replacement doses).
- history of central nervous system (CNS) disorders such as seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychosis; untreated or symptomatic CNS metastases or cytologically confirmed carcinomatous meningitis (asymptomatic CNS metastases that do not require treatment may be enrolled).
- left ventricular ejection fraction <50%.
- White blood cell count <3×10^9/L and platelet count <80×10^9/L.
- AST and ALT > 3 × upper limit of normal (ULN)
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- Total bilirubin > 1.5 × ULN.
- creatinine clearance <60 ml/min.
- Abnormal coagulation function (activated partial thromboplastin time (APTT) > 1.5 × ULN, international normalized ratio (INR) > 1.5 × ULN).
- patients with intestinal obstruction (gastrointestinal obstruction within 30 days prior to administration).
- patients with infectious diseases including, but not limited to: 1) known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related disease; 2) known active liver disease, including hepatitis B and hepatitis C; 3) active tuberculosis infection, who are on anti-tuberculosis treatment or who have received anti-tuberculosis treatment within 1 year prior to the first dose of the study drug; 4) known syphilis infections requiring treatment; and 5) Other infectious diseases that, in the judgment of the investigator, make participation in this study unsuitable.
- Diseases that, in the judgment of the investigator, preclude enrollment: including, but not limited to, severe hepatic, renal, or metabolic disease requiring drug therapy, uncontrolled coronary artery disease or asthma, and uncontrolled cerebrovascular disease.
- pregnant or breastfeeding females; females or males of childbearing age with a pregnancy plan during the study.
- psychotropic substance abuse, clinical or psychological or social factors that would compromise informed consent or study conduct (at the discretion of the investigator).
- individuals who may be allergic to the study medication.
- is participating in another clinical trial.
- patients with inaccessible peripheral or deep venous access.
- any uncertainty that has an impact on patient safety or compliance.
- any other condition that the investigator considers inappropriate for enrollment.
Trial locations and contacts
1 site in 1 country.
Song Zheng, Doctor contact
China1 site
Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310002
About this study
Official title: Human HER2-targeted Chimeric Antigen Receptor Macrophages Therapy for HER2-positive Advanced Gastric Cancer With Peritoneal Metastases: an Exploratory Clinical Trial
The goal of this exploratory clinical trial is to evaluate the safety and efficacy of human anti-human epidermal growth factor receptor 2(HER2) Chimeric antigen receptor macrophage cells (CAR-M) in advanced HER2+ gastric cancer. Participants will mobilize bone marrow stem cells and engineer autologous macrophages to express Chimeric antigen receptor (CAR), and CAR-M will be infused intraperitoneally back into the patient for systemic anti-tumor effects.
Read the detailed description
The standard approach for managing advanced peritoneal metastatic gastric cancer typically involves systemic administration of antitumor drugs. In the case of HER2-positive gastric cancer patients, a combination of trastuzumab, platinum, and fluorouracil chemotherapeutic agents is commonly employed. Nevertheless, conventional therapy encounters obstacles stemming from tumor heterogeneity and the intricate microenvironment. The self-developed humanized anti-HER2 chimeric antigen receptor macrophage (human anti-HER2 CAR-M) uses an adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to human HER2 antigens to recognize and kill tumor cells. Cell and animal experiments as well as preclinical trials showed that anti-human HER2 CAR M cells have significant anti-tumor efficacy and good safety. This study can provide abundant clinical data for the safety and feasibility of CAR macrophage therapy for solid tumors, and promote the progress of CAR macrophage therapy for solid tumors.
- Conditions
- Gastric Cancer
- Being tested
- human HER2-targeted CAR-M cells
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
human HER2-targeted CAR-M cellsBiological
Also called anti-HER2 CAR-M cells
The human anti-HER2 chimeric antigen receptor macrophages (anti-HER2 CAR-M cells) independently developed use adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to the human HER2 antigen to recognize and kill tumor cells.
| Study group | Role | What they receive |
|---|---|---|
| human HER2-targeted CAR-M cell | Experimental | Recombinant human granulocyte stimulating factor treatment mobilized bone marrow stem cells, when the mononuclear cells rose to more than 8×10^8/L, the collection of peripheral blood single nuclei cells, the total number of mononuclear cells collected 1.5×10^9-1.8×10^9. Intraperitoneal infusion of anti-human HER2 CAR-M cells 3×10^8 cells/person, in a single administration.According to the principle of "3+3 dose increment", enter dose 2 and dose 3. Dose2: the monocyte rises to more than 9.5×10^8/L and collect peripheral blood single nucleus cells. Reinfuse anti-human HER2 CAR-M cells 5×10^8 cells/person, 1 person/bag/dose, 100 ml/bag. Dose3: the mononuclear cell rises to more than 1.3×10^9/L and collect peripheral blood single nucleus cells. Reinfuse anti-human HER2 CAR-M cells 1×10^9 cells/person, 1 person/bag/dose, 200 ml/bag. Receives: Biological: human HER2-targeted CAR-M cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse effects
Collect information on the type, frequency, and severity of adverse events.Identify and grade adverse events following CTCAE 5.0 criteria.
Measured: The evaluation was conducted within 28 days of administration, with a total of 30 recording points
Secondary outcomes (5)
Time to Sustained Remission (DOR)
Solid tumor efficacy was assessed following the RECIST 1.1 criteria, calculating the time from first onset of efficacy (i.e., complete remission (CR) or partial remission (PR)), to earliest disease progression or death.
Measured: 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months post-infusion.
Overall response rate (ORR)
Solid tumor efficacy was assessed following RECIST 1.1 criteria, and the proportion of subjects in complete or partial remission was calculated.
Measured: Initiation of the first evaluation of the tumor as CR or PR to the beginning of the -th evaluation as progressive disease (PD) or death from any cause.
Disease Control Rate (DCR)
The RECIST 1.1 criteria were followed to assess the efficacy of solid tumors, and DCR was defined as the number of cases that achieved remission (CR+PR) and stable disease (SD) after treatment as a percentage of the number of evaluable cases.
Measured: Assessed every month, up to 3 months.
Progression-free survival (PFS)
Solid tumor efficacy was assessed following the RECIST 1.1 criteria by calculating the time between infusion and the first record of disease progression or death.
Measured: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival (OS)
Calculation of time from infusion to death from any cause.
Measured: From date of randomization until the date of death from any cause, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start1 Mar 2024 (estimated)
- Primary completion1 Mar 2025 (estimated)
- Study completion1 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First People's Hospital of Hangzhou
- Sponsor type
- University, hospital or other
- Collaborators
- Macera therapeutics
- Responsible party
- Principal investigator, Bing Xia, First People's Hospital of Hangzhou
- Investigators
- Bing Xia, Principal investigator, First People's Hospital of Hangzhou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06224738
- Sponsor's protocol ID
- ITT-20231107-0257-02
- Status last verified
- Jan 2024
- First submitted
- 24 Dec 2023
- Last updated
- 25 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhang W, Liu L, Su H, Liu Q, Shen J, Dai H, Zheng W, Lu Y, Zhang W, Bei Y, Shen P. Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix. Br J Cancer. 2019 Nov;121(10):837-845. doi: 10.1038/s41416-019-0578-3. Epub 2019 Oct 1.
PubMed 31570753Dong X, Fan J, Xie W, Wu X, Wei J, He Z, Wang W, Wang X, Shen P, Bei Y. Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer. Br J Cancer. 2023 Aug;129(3):551-562. doi: 10.1038/s41416-023-02319-6. Epub 2023 Jun 29.
PubMed 37386139
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human HER2-targeted Chimeric Antigen Receptor Macrophages Therapy for HER2-positive Advanced Gastric Cancer With Peritoneal Metastases: an Exploratory Clinical Trial
- ClinicalTrials.gov ID
- NCT06224738
- Acronym / sponsor ID
- ITT-20231107-0257-02
- Conditions
- Gastric Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- First People's Hospital of HangzhouUniversity, hospital or other
- Collaborators
- Macera therapeutics
- Study start
- 1 Mar 2024 (estimated)
- Primary completion
- 1 Mar 2025 (estimated)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 25 Jan 2024 (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 goal of this exploratory clinical trial is to evaluate the safety and efficacy of human anti-human epidermal growth factor receptor 2(HER2) Chimeric antigen receptor macrophage cells (CAR-M) in advanced HER2+ gastric cancer. Participants will mobilize bone marrow stem cells and engineer autologous macrophages to express Chimeric antigen receptor (CAR), and CAR-M will be infused intraperitoneally back into the patient for systemic anti-tumor effects.
Detailed description
The standard approach for managing advanced peritoneal metastatic gastric cancer typically involves systemic administration of antitumor drugs. In the case of HER2-positive gastric cancer patients, a combination of trastuzumab, platinum, and fluorouracil chemotherapeutic agents is commonly employed. Nevertheless, conventional therapy encounters obstacles stemming from tumor heterogeneity and the intricate microenvironment. The self-developed humanized anti-HER2 chimeric antigen receptor macrophage (human anti-HER2 CAR-M) uses an adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to human HER2 antigens to recognize and kill tumor cells. Cell and animal experiments as well as preclinical trials showed that anti-human HER2 CAR M cells have significant anti-tumor efficacy and good safety. This study can provide abundant clinical data for the safety and feasibility of CAR macrophage therapy for solid tumors, and promote the progress of CAR macrophage therapy for solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| human HER2-targeted CAR-M cell | Experimental | Biological: human HER2-targeted CAR-M cellsRecombinant human granulocyte stimulating factor treatment mobilized bone marrow stem cells, when the mononuclear cells rose to more than 8×10^8/L, the collection of peripheral blood single nuclei cells, the total number of mononuclear cells collected 1.5×10^9-1.8×10^9. Intraperitoneal infusion of anti-human HER2 CAR-M cells 3×10^8 cells/person, in a single administration.According to the principle of "3+3 dose increment", enter dose 2 and dose 3. Dose2: the monocyte rises to more than 9.5×10^8/L and collect peripheral blood single nucleus cells. Reinfuse anti-human HER2 CAR-M cells 5×10^8 cells/person, 1 person/bag/dose, 100 ml/bag. Dose3: the mononuclear cell rises to more than 1.3×10^9/L and collect peripheral blood single nucleus cells. Reinfuse anti-human HER2 CAR-M cells 1×10^9 cells/person, 1 person/bag/dose, 200 ml/bag. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- age between 18 and 75 years (including borderline values), male or female.
- expected survival of more than 12 weeks.
- histologically confirmed HER2-positive gastric cancer; HER2-positive is defined as immunohistochemistry (IHC) 3+ or (IHC) 2+ with in situ hybridization (ISH) +.
- confirmation of peritoneal metastasis by imaging or cytologic testing of peritoneal fluid.
- presence of measurable lesions.
Key exclusion criteria (19 listed)
- previous or current other types of malignant tumors, except for the following: completely resected or eradicated basal and squamous cell carcinoma of the skin, and carcinoma in situ of the cervix.
- patients requiring immunosuppressive drugs (except physiologic replacement doses).
- history of central nervous system (CNS) disorders such as seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychosis; untreated or symptomatic CNS metastases or cytologically confirmed carcinomatous meningitis (asymptomatic CNS metastases that do not require treatment may be enrolled).
- left ventricular ejection fraction <50%.
- White blood cell count <3×10^9/L and platelet count <80×10^9/L.
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 |
|---|---|---|
| human HER2-targeted CAR-M cellsAlso: anti-HER2 CAR-M cellsThe human anti-HER2 chimeric antigen receptor macrophages (anti-HER2 CAR-M cells) independently developed use adenoviral vector system to genetically engineer autologous macrophages to express CAR molecules containing single-chain antibodies, which specifically bind to the human HER2 antigen to recognize and kill tumor cells. | Biological | human HER2-targeted CAR-M cell |
Primary outcome
Adverse effects
Time frame: The evaluation was conducted within 28 days of administration, with a total of 30 recording points
Collect information on the type, frequency, and severity of adverse events.Identify and grade adverse events following CTCAE 5.0 criteria.
5 secondary outcomes
Time to Sustained Remission (DOR)
Time frame: 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months post-infusion.
Overall response rate (ORR)
Time frame: Initiation of the first evaluation of the tumor as CR or PR to the beginning of the -th evaluation as progressive disease (PD) or death from any cause.
Disease Control Rate (DCR)
Time frame: Assessed every month, up to 3 months.
Progression-free survival (PFS)
Time frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Overall Survival (OS)
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- Background: PubMed 31570753Zhang W, Liu L, Su H, Liu Q, Shen J, Dai H, Zheng W, Lu Y, Zhang W, Bei Y, Shen P. Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix. Br J Cancer. 2019 Nov;121(10):837-845. doi: 10.1038/s41416-019-0578-3. Epub 2019 Oct 1.
- Background: PubMed 37386139Dong X, Fan J, Xie W, Wu X, Wei J, He Z, Wang W, Wang X, Shen P, Bei Y. Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer. Br J Cancer. 2023 Aug;129(3):551-562. doi: 10.1038/s41416-023-02319-6. Epub 2023 Jun 29.
- Individual participant dataSharing planned: No
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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.
Song Zheng, Doctor contact
Bing Xia principal investigator
First People's Hospital of Hangzhou
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing human HER2-targeted CAR-M cells in people with Gastric Cancer, run by First People's Hospital of Hangzhou 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 12 inclusion and 19 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 25 Jan 2024. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Bing Xia, Doctor ((+86)18857210928, bxia_hzch@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse effects (time frame: The evaluation was conducted within 28 days of administration, with a total of 30 recording points). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06224738, which also lists 2 linked publications.
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 25 Jan 2024.