Colorectal NeoplasiaPhase 1NCT06946615
Exploratory Clinical Study of Claudin18.2-Targeted CAR-DC and CAR-T Therapy in Advanced Colorectal Cancer
A Phase 1 study testing Claudin18.2-targeted CAR-T Cells and Claudin18.2-targeted CAR-DCs in people with Colorectal Neoplasia, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Neoplasia
- What is being tested?
- Claudin18.2-targeted CAR-T Cells and Claudin18.2-targeted CAR-DCs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 8 Apr 2025to Apr 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have a histologically or cytologically confirmed diagnosis of colonic or rectal adenocarcinoma, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
- Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
- Disease progression following standard treatments, including prior administration of fluoropyrimidines, irinotecan, and oxaliplatin. Disease progression may occur during or after treatment. Prior molecular targeted therapies are allowed.
- ECOG performance status of 0 to 1.
- Expected survival of at least 6 months.
- Toxicities related to prior antitumor treatments must have resolved to baseline or ≤ Grade 1 (except for residual alopecia); peripheral neurotoxicity ≤ Grade 2 is acceptable. The minimum washout period is 4 weeks for chemotherapy and immunotherapy, and 2 weeks for targeted therapy.
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- Adequate organ function, defined as follows:
- Hematologic function: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 75 × 10^9/L, and hemoglobin ≥ 9 g/dL. No blood transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), or erythropoietin (EPO) allowed within 14 days prior to hematology testing.
- Hepatic function: Total bilirubin (TBIL) < 1.5 × upper limit of normal (ULN); AST and ALT < 2.5 × ULN. For patients with Gilbert's syndrome, TBIL < 2 × ULN. For patients with liver metastases, AST and ALT must be < 5 × ULN.
- Renal function: Serum creatinine ≤ 1.5 × ULN; or if > 1.5 × ULN, creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockcroft-Gault formula.
- Coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) < 1.5 × ULN; international normalized ratio (INR) < 1.5 or within the therapeutic range if on anticoagulation therapy.
- Participants of childbearing potential must agree to use effective contraception during the study period.
- Participants must have adequate comprehension and voluntarily sign the informed consent form.
- Willingness to comply with all study-related procedures, including scheduled visits, drug administration, laboratory assessments, and other protocol requirements.
Who cannot join
- Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
- Clinically significant cardiovascular disease, including:
- Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmias, or history of angioplasty, stent implantation, or coronary artery bypass grafting (CABG);
- Prolonged QT/QTcF interval with clinical significance (QT/QTcF > 470 ms in females or > 450 ms in males).
- Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
- Active infections including HIV, syphilis, or active hepatitis B or C:
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- Hepatitis B: HBV-DNA ≥ 1000 IU/mL;
- Hepatitis C: Positive HCV RNA with abnormal liver function.
- History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
- Presence of autoimmune diseases or chronic use of immunosuppressive agents or corticosteroids.
- Poor medication compliance or inability to adhere to the treatment protocol.
- Any other condition that, in the opinion of the investigator, warrants exclusion from the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
Ying Yuan, +86-13858193601, yuanying1999@zju.edu.cn
About this study
Official title: Exploratory Clinical Study of Combined Claudin18.2-Targeted CAR-DC and CAR-T Therapy in Patients With Advanced Colorectal Cancer
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colorectal cancer.
Read the detailed description
Main purpose:
To evaluate the safety of Claudin18.2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced colorectal cancer during the dose-escalation phase.
To determine the maximum tolerated dose of Claudin18.2-targeted CAR-DCs when administered in combination with CAR-T cells.
Secondary purpose:
To assess the overall response rate (ORR), including complete response (CR) and partial response (PR), as well as overall survival (OS) and disease-free survival (DFS) in patients receiving the combination therapy.
To evaluate the in vivo persistence, immunophenotype, and functional activity of CAR-T cells and CAR-DCs following infusion.
- Conditions
- Colorectal Neoplasia
- Being tested
- Claudin18.2-targeted CAR-T Cells, Claudin18.2-targeted CAR-DCs
- Keywords
- Chimeric Antigen Receptor Dendritic Cells, Chimeric Antigen Receptor T-Cells, Colorectal Neoplasms
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Claudin18.2-targeted CAR-T CellsBiological
Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2.
Claudin18.2-targeted CAR-DCsBiological
Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2.
| Study group | Role | What they receive |
|---|---|---|
| CAR-T and CAR-DC Combination Therapy | Experimental | This arm involves the sequential administration of two biological interventions, with Claudin18.2-targeted CAR-DCs administered first, followed by Claudin18.2-targeted CAR-T cells. Receives: Biological: Claudin18.2-targeted CAR-T Cells; Biological: Claudin18.2-targeted CAR-DCs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Incidence and severity of adverse events
To evaluate adverse events occurring within the first three months following infusion of Claudin18.2-targeted CAR-T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Measured: First 3 month post CAR-T cells and CAR-DCs infusion
Efficacy: Remission Rate
To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)
Measured: 3 months post CAR-T cells and CAR-DCs infusion
Secondary outcomes (7)
Progression-Free Survival
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
Overall Survival
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
Relapse Rate
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
Duration of Response
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring
The copy number of CAR-T cells and CAR-DCs in PBMCs will be measured by qPCR to assess in vivo persistence.
Serum cytokine levels, including IL-2, IL-4, IL-6, IFN-γ, TNF-α, IL-10, IL-12, and IL-17A, will be quantified by ELISA to evaluate immune activation following cell infusion.
Measured: First 2 weeks post CAR-T cells and CAR-DCs infusion
Objective Response Rate in Participants Receiving Different Doses of CAR-DCs
The proportion of participants in each CAR-DCs dose cohort (5×10^6, 1×10^7, 3×10^7, and 9×10^7 cells) who achieve an objective tumor response, including complete remission (CR) or partial remission (PR). All participants received a fixed dose of Claudin18.2-targeted CAR-T cells (2×10^6 cells/kg) following CAR-DCs infusion.
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs
To evaluate adverse events occurring following infusion of Claudin18.2-targeted CAR-DCs and CAR-T cells. Participants will receive CAR-DCs at one of four dose levels (5×10^6, 1×10^7, 3×10^7, and 9×10^7 cells), followed by a fixed dose of Claudin18.2-targeted CAR-T cells (2×10^6 cells/kg). The assessment includes the incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Measured: Up to 24 months post CAR-T cells and CAR-DCs infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2025
- Study start8 Apr 2025
- Primary completionApr 2026 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasiaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ying Yuan, Principal investigator, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06946615
- Sponsor's protocol ID
- 2024-0255
- Status last verified
- Apr 2025
- First submitted
- 10 Apr 2025
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Clinical Study of Combined Claudin18.2-Targeted CAR-DC and CAR-T Therapy in Patients With Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06946615
- Acronym / sponsor ID
- 2024-0255
- Conditions
- Colorectal Neoplasia
- Keywords
- Chimeric Antigen Receptor Dendritic Cells, Chimeric Antigen Receptor T-Cells, Colorectal Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 8 Apr 2025 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 27 Apr 2025 (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 an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colorectal cancer.
Detailed description
Main purpose:
To evaluate the safety of Claudin18.2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced colorectal cancer during the dose-escalation phase.
To determine the maximum tolerated dose of Claudin18.2-targeted CAR-DCs when administered in combination with CAR-T cells.
Secondary purpose:
To assess the overall response rate (ORR), including complete response (CR) and partial response (PR), as well as overall survival (OS) and disease-free survival (DFS) in patients receiving the combination therapy.
To evaluate the in vivo persistence, immunophenotype, and functional activity of CAR-T cells and CAR-DCs following infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T and CAR-DC Combination Therapy | Experimental | Biological: Claudin18.2-targeted CAR-T Cells, Biological: Claudin18.2-targeted CAR-DCsThis arm involves the sequential administration of two biological interventions, with Claudin18.2-targeted CAR-DCs administered first, followed by Claudin18.2-targeted CAR-T cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Participants must have a histologically or cytologically confirmed diagnosis of colonic or rectal adenocarcinoma, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
- Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
- Disease progression following standard treatments, including prior administration of fluoropyrimidines, irinotecan, and oxaliplatin. Disease progression may occur during or after treatment. Prior molecular targeted therapies are allowed.
- ECOG performance status of 0 to 1.
- Expected survival of at least 6 months.
Key exclusion criteria (12 listed)
- Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
- Clinically significant cardiovascular disease, including:
- Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
- Active infections including HIV, syphilis, or active hepatitis B or C:
- History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
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 |
|---|---|---|
| Claudin18.2-targeted CAR-T CellsAutologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2. | Biological | CAR-T and CAR-DC Combination Therapy |
| Claudin18.2-targeted CAR-DCsAutologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2. | Biological | CAR-T and CAR-DC Combination Therapy |
Primary outcome
Safety: Incidence and severity of adverse events
Time frame: First 3 month post CAR-T cells and CAR-DCs infusion
To evaluate adverse events occurring within the first three months following infusion of Claudin18.2-targeted CAR-T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.
Efficacy: Remission Rate
Time frame: 3 months post CAR-T cells and CAR-DCs infusion
To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)
7 secondary outcomes
Progression-Free Survival
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Overall Survival
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Relapse Rate
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Duration of Response
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring
Time frame: First 2 weeks post CAR-T cells and CAR-DCs infusion
Objective Response Rate in Participants Receiving Different Doses of CAR-DCs
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Incidence and Severity of Treatment-Related Adverse Events in Participants Receiving Different Doses of CAR-DCs
Time frame: Up to 24 months post CAR-T cells and CAR-DCs infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
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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.
Ying Yuan principal investigator
Second Affiliated Hospital, Zhejiang University, School of Medicine
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 Claudin18.2-targeted CAR-T Cells and Claudin18.2-targeted CAR-DCs in people with Colorectal Neoplasia, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 14 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 27 Apr 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ying Yuan (+86-13858193601, yuanying1999@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Incidence and severity of adverse events (time frame: First 3 month post CAR-T cells and CAR-DCs infusion). The study lists 2 primary outcomes in all. 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 27 Apr 2025.