Anti-CEA CAR-T Cells to Treat Colorectal Liver Metastases

Launched by CHANGHAI HOSPITAL · Feb 13, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new type of treatment called Anti-CEA CAR-T cell therapy for patients with colorectal cancer that has spread to the liver. After surgery to remove the main tumor, some patients still have tiny amounts of cancer that can’t be seen on scans, called minimal residual disease (MRD). This trial aims to test the safety and effectiveness of this CAR-T cell therapy in patients whose blood tests show signs of MRD after their surgery. The researchers hope to find the right dose of the treatment that patients can tolerate and gather information that can help with future studies.

To be eligible for this trial, participants must be between 18 and 75 years old and have undergone surgery for their colorectal cancer, resulting in no visible tumors but still showing signs of MRD. They should also have a specific level of a tumor marker called CEA in their tissue. Participants can expect to receive this new therapy and be closely monitored for its effects and any side effects. It’s important to note that certain health conditions and treatments might prevent someone from joining the study, so potential participants will be carefully evaluated before enrollment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. ≥18 years old, ≤75 years old, male or female;
• • 2. 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;
• • 3. Patients with CEA expression detected by immunohistochemistry in primary tumor and liver metastasis tumor tissues (CEA expression detected by pathology was more than 50%);
• • 4. Life expectancy ≥6 months;
• • 5. Performance status (PS) score 0-2, Karnofsky performance status (KPS) score above 60;
• • 6. Patients with ctDNA MRD still positive or positive again after adjuvant chemotherapy (including preoperative neoadjuvant chemotherapy);
• • 7. 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);
• • 8. Sufficient mononuclear cells (PBMC) can be obtained from peripheral veins without contraindications;
• • 9. Patients of childbearing age had no birth plan within 1 year after cell infusion and took effective contraceptive measures.
• Exclusion Criteria:
• • 1. Have a history of severe central nervous system diseases;
• • 2. Residual disease or tumor remnants can be seen in imaging, or tumor lesions cannot be resected in other tissues or organs;
• • 3. The presence of serious non-malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
• • 4. Prior treatment with CAR-T or other gene-modified T cells;
• • 5. Participated in other clinical studies within 30 days prior to screening or plan to participate in other clinical studies during the study period;
• • 6. 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;
• • 7. The existence of uncontrollable systemic infectious diseases;
• • 8. Other multiple malignant tumors in addition to colorectal cancer and its metastasis;
• • 9. 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;
• • 10. Pregnancy and lactation;
• • 11. The existence of severe gastroduodenal ulcer, severe ulcerative colitis and other serious intestinal inflammation;
• • 12. The existence of serious respiratory diseases;
• • 13. Those who cannot provide enough white tablets for tumor pathology for next-generation sequencing (NGS) detection (at least 3 white tablets are expected);
• • 14. The investigator judged that there were other conditions that were not suitable for the clinical study.