Anti-CEA CAR-T Cells to Treat Colorectal Liver Metastases
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorChanghai Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
≥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;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
Anti-CEA CAR-T Cells
DrugThe 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.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: MRD or positive ctDNA patients to inject anti-CEA CAR-T cellsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
Observation 28 days after CAR-T cells infusion2
Effectiveness (minimal residual disease)
Recurrence by ctDNA MRD detection or imaging diagnosis
Time frame
24 months after R0 resection3
Efficacy (recurrence-free survival)
2-year recurrence-free survival rate based on imageological examination.
Time frame
2 years after CAR-T cells infusionSecondary outcomes
1
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).
Time frame
2 years after CAR-T cells infusion2
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).
Time frame
2 years after CAR-T cells infusionSponsors and contacts
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Source ClinicalTrials.gov