Colorectal CancerPhase 1NCT05240950
Anti-CEA CAR-T Cells to Treat Colorectal Liver Metastases
A Phase 1 study testing Anti-CEA CAR-T Cells in people with Colorectal Cancer and Metastatic Liver Cancer, run by Changhai Hospital at 1 site in China.
Trial summary
Recurrence of liver metastasis in colorectal cancer after R0 resection is mainly due to the invisible minimal residual disease, which are the main factors leading to metastasis and recurrence. Positive circulating tumor DNA (ctDNA) is the direct evidence of the minimal residual disease (MRD). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Metastatic Liver Cancer
- What is being tested?
- Anti-CEA CAR-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 25 Aug 2022to 25 Dec 2026
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years old, ≤75 years old, male or female;
- Patients diagnosed with liver metastasis of colorectal cancer underwent radical surgery for the primary lesion of colorectal cancer, and R0 resection was performed for the liver metastasis (R0 resection was required for other organ metastasis). There was no measurable disease or tumor remnants (except invisible or unmeasurable disease) were found by imaging examination after surgery;
- Patients with CEA expression detected by immunohistochemistry in primary tumor and liver metastasis tumor tissues (CEA expression detected by pathology was more than 50%);
- Life expectancy ≥6 months;
- Performance status (PS) score 0-2, Karnofsky performance status (KPS) score above 60;
- Patients with ctDNA MRD still positive or positive again after adjuvant chemotherapy (including preoperative neoadjuvant chemotherapy);
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- Important organ functions are sufficient, such as New York Heart Association (NYHA) heart function grade III or above, hemoglobin ≥90g/L, hypoxia; Liver function: total bilirubin ≤1.5×ULN (total bilirubin ≤3×ULN in liver metastasis), ALT≤2.5×ULN, AST≤2.5×ULN (ALT or/and AST≤5×ULN in liver metastasis); Renal function: serum creatinine ≤1.5×ULN and creatinine clearance rate ≥50 mL/min. The creatinine clearance rate was only calculated when serum creatinine ≤1.5×ULN. Minimum reserve of lung function (dyspnea no higher than grade 1 and oxygen saturation > 91% without oxygen);
- Sufficient mononuclear cells (PBMC) can be obtained from peripheral veins without contraindications;
- Patients of childbearing age had no birth plan within 1 year after cell infusion and took effective contraceptive measures.
Who cannot join
- Have a history of severe central nervous system diseases;
- Residual disease or tumor remnants can be seen in imaging, or tumor lesions cannot be resected in other tissues or organs;
- The presence of serious non-malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
- Prior treatment with CAR-T or other gene-modified T cells;
- Participated in other clinical studies within 30 days prior to screening or plan to participate in other clinical studies during the study period;
- Patients with active Hepatitis B (HBV-DNA copy number >105copies/ml), active Hepatitis C (HCV-RNA copy number >ULN), HIV infection, treponema pallidum infection at screening time;
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- The existence of uncontrollable systemic infectious diseases;
- Other multiple malignant tumors in addition to colorectal cancer and its metastasis;
- Chinese herbal medicine, systemic glucocorticoids or other immunosuppressants may be required within 2 weeks prior to enrollment or during the trial period, which may negatively affect lymphocyte activity or number;
- Pregnancy and lactation;
- The existence of severe gastroduodenal ulcer, severe ulcerative colitis and other serious intestinal inflammation;
- The existence of serious respiratory diseases;
- Those who cannot provide enough white tablets for tumor pathology for next-generation sequencing (NGS) detection (at least 3 white tablets are expected);
- The investigator judged that there were other conditions that were not suitable for the clinical 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
Department of Colorectal Surgery in Changhai Hospital
Shanghai, Shanghai Municipality, 200433
Wei Zhang, 021-31161613, weizhang2000cn@163.com
About this study
Official title: A Clinical Study to Evaluate the Safety and Efficacy of Anti-CEA CAR-T Cells in the Treatment of Postoperative Minimal Residual Lesions in Colorectal Cancer Patients With Liver Metastases
Recurrence of liver metastasis in colorectal cancer after R0 resection is mainly due to the invisible minimal residual disease, which are the main factors leading to metastasis and recurrence. Positive circulating tumor DNA (ctDNA) is the direct evidence of the minimal residual disease (MRD). In recent years, Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) has made great breakthroughs, and has achieved good therapeutic effects in hematological tumors, but the research on solid tumors is limited. CEA expression is generally elevated in gastrointestinal tumors and is associated with high aggressiveness of tumors. At present, solid tumor cell therapy targeting CEA has been carried out at home and abroad, and has achieved certain efficacy. Anti-CEA CAR-T cells targeting CEA have been constructed in the pre-clinical study of this project, and the pre-clinical study results suggest good safety and effectiveness. Formation of minimal residual disease is associated with circulating blood in the residual tumor cells. Using this feature, this project intends to conduct a phase I clinical study on patients with minimal residual disease /positive ctDNA after R0 resection of colorectal cancer liver metastasis, so as to conduct preliminary exploration of anti-CEA CAR-T cell therapy, evaluate the safety and effectiveness of the therapy, determine the maximum tolerated dose (MTD), and provide guidance for subsequent drug dosage and clinical trials.
- Conditions
- Colorectal Cancer, Metastatic Liver Cancer
- Being tested
- Anti-CEA CAR-T Cells
- Keywords
- colorectal cancer, liver metastasis, CAR-T cell, minimal residue disease
- Medical subject headings
- Colorectal Neoplasms, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CEA CAR-T CellsDrug
The study will evaluate the safety of intravenous infusion of anti-CEA CAR-T (+) cells in humans at doses of 1×10^6/kg, 3×10^6/kg, and 6×10^6/kg using a standard "3+3" design and preliminarily observe the efficacy.
| Study group | Role | What they receive |
|---|---|---|
| MRD or positive ctDNA patients to inject anti-CEA CAR-T cells | Experimental | Patients with liver metastasis of colorectal cancer after R0 surgery and adjuvant chemotherapy could not clear MRD (including patients with MRD still positive after the intermediate and final evaluation of adjuvant chemotherapy, and patients with MRD positive again after the end of adjuvant chemotherapy), and no measurable lesions or tumor remnants were found on imaging after surgery. Receives: Drug: Anti-CEA CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Security (Incidence and severity of adverse events)
To evaluate the possible reatment related adverse events(TEAEs) occurred within the first 28 days after anti-CEA CAR-T infusion, including replicative lentiviruses(RCL), anti-drug antibody(ADA), and the incidence and severity of symptoms such as cytokine release syndrome(CRS) and CAR-T related encephalopathy syndrome(CRES).
Measured: Observation 28 days after CAR-T cells infusion
Effectiveness (minimal residual disease)
Recurrence by ctDNA MRD detection or imaging diagnosis
Measured: 24 months after R0 resection
Efficacy (recurrence-free survival)
2-year recurrence-free survival rate based on imageological examination.
Measured: 2 years after CAR-T cells infusion
Secondary outcomes (2)
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of anti-CEA CAR-T cells amplified in the peripheral blood (Cmax, detected by flow cytometry and qPCR).
Measured: 2 years after CAR-T cells infusion
Pharmacokinetics (PK) indicator (AUC)
The exposed quantity of anti-CEA CAR-T cells amplified in the peripheral blood(aera under the curve, AUC, detected by flow cytometry and qPCR).
Measured: 2 years after CAR-T cells infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2022
- Study start25 Aug 2022 (estimated)
- Primary completion25 Dec 2023 (estimated)
- Study completion25 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Changhai 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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei Zhang, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05240950
- Sponsor's protocol ID
- CHCRS-CEA CAR-T
- Status last verified
- Mar 2022
- First submitted
- 26 Dec 2021
- Last updated
- 11 Mar 2022
- 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 11 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Evaluate the Safety and Efficacy of Anti-CEA CAR-T Cells in the Treatment of Postoperative Minimal Residual Lesions in Colorectal Cancer Patients With Liver Metastases
- ClinicalTrials.gov ID
- NCT05240950
- Acronym / sponsor ID
- CHCRS-CEA CAR-T
- Conditions
- Colorectal Cancer, Metastatic Liver Cancer
- Keywords
- colorectal cancer, liver metastasis, CAR-T cell, minimal residue disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Study start
- 25 Aug 2022 (estimated)
- Primary completion
- 25 Dec 2023 (estimated)
- Study completion
- 25 Dec 2026 (estimated)
- First posted
- 15 Feb 2022 (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.
Recurrence of liver metastasis in colorectal cancer after R0 resection is mainly due to the invisible minimal residual disease, which are the main factors leading to metastasis and recurrence. Positive circulating tumor DNA (ctDNA) is the direct evidence of the minimal residual disease (MRD). In recent years, Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) has made great breakthroughs, and has achieved good therapeutic effects in hematological tumors, but the research on solid tumors is limited. CEA expression is generally elevated in gastrointestinal tumors and is associated with high aggressiveness of tumors. At present, solid tumor cell therapy targeting CEA has been carried out at home and abroad, and has achieved certain efficacy. Anti-CEA CAR-T cells targeting CEA have been constructed in the pre-clinical study of this project, and the pre-clinical study results suggest good safety and effectiveness. Formation of minimal residual disease is associated with circulating blood in the residual tumor cells. Using this feature, this project intends to conduct a phase I clinical study on patients with minimal residual disease /positive ctDNA after R0 resection of colorectal cancer liver metastasis, so as to conduct preliminary exploration of anti-CEA CAR-T cell therapy, evaluate the safety and effectiveness of the therapy, determine the maximum tolerated dose (MTD), and provide guidance for subsequent drug dosage and clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MRD or positive ctDNA patients to inject anti-CEA CAR-T cells | Experimental | Drug: Anti-CEA CAR-T CellsPatients with liver metastasis of colorectal cancer after R0 surgery and adjuvant chemotherapy could not clear MRD (including patients with MRD still positive after the intermediate and final evaluation of adjuvant chemotherapy, and patients with MRD positive again after the end of adjuvant chemotherapy), and no measurable lesions or tumor remnants were found on imaging after surgery. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥18 years old, ≤75 years old, male or female;
- Patients diagnosed with liver metastasis of colorectal cancer underwent radical surgery for the primary lesion of colorectal cancer, and R0 resection was performed for the liver metastasis (R0 resection was required for other organ metastasis). There was no measurable disease or tumor remnants (except invisible or unmeasurable disease) were found by imaging examination after surgery;
- Patients with CEA expression detected by immunohistochemistry in primary tumor and liver metastasis tumor tissues (CEA expression detected by pathology was more than 50%);
- Life expectancy ≥6 months;
- Performance status (PS) score 0-2, Karnofsky performance status (KPS) score above 60;
Key exclusion criteria (14 listed)
- Have a history of severe central nervous system diseases;
- Residual disease or tumor remnants can be seen in imaging, or tumor lesions cannot be resected in other tissues or organs;
- The presence of serious non-malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
- Prior treatment with CAR-T or other gene-modified T cells;
- Participated in other clinical studies within 30 days prior to screening or plan to participate in other clinical studies during the study period;
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 |
|---|---|---|
| Anti-CEA CAR-T CellsThe study will evaluate the safety of intravenous infusion of anti-CEA CAR-T (+) cells in humans at doses of 1×10^6/kg, 3×10^6/kg, and 6×10^6/kg using a standard "3+3" design and preliminarily observe the efficacy. | Drug | MRD or positive ctDNA patients to inject anti-CEA CAR-T cells |
Primary outcome
Security (Incidence and severity of adverse events)
Time frame: Observation 28 days after CAR-T cells infusion
To evaluate the possible reatment related adverse events(TEAEs) occurred within the first 28 days after anti-CEA CAR-T infusion, including replicative lentiviruses(RCL), anti-drug antibody(ADA), and the incidence and severity of symptoms such as cytokine release syndrome(CRS) and CAR-T related encephalopathy syndrome(CRES).
Effectiveness (minimal residual disease)
Time frame: 24 months after R0 resection
Recurrence by ctDNA MRD detection or imaging diagnosis
Efficacy (recurrence-free survival)
Time frame: 2 years after CAR-T cells infusion
2-year recurrence-free survival rate based on imageological examination.
2 secondary outcomes
Pharmacokinetics (PK) indicator (Cmax)
Time frame: 2 years after CAR-T cells infusion
Pharmacokinetics (PK) indicator (AUC)
Time frame: 2 years after CAR-T cells 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 11 Mar 2022.
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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.
Department of Colorectal Surgery in Changhai Hospital
Shanghai, China
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 Anti-CEA CAR-T Cells in people with Colorectal Cancer and Metastatic Liver Cancer, run by Changhai 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 9 inclusion and 14 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 11 Mar 2022. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Security (Incidence and severity of adverse events) (time frame: Observation 28 days after CAR-T cells infusion). The study lists 3 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 11 Mar 2022.