An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CEA-CAR-T Cells Injection in Patients With CEA+ Locally Advanced and/or Metastatic Solid Tumors

NCT06013111 | Recruiting Phase 1

• 1 other identifier: CEA-CN-A3
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label clinical study of anti-CEA-CAR-T cells for CEA+ patients with locally advanced and/or metastatic solid tumors. In this study, a single-dose regimen was designed, and the investigator had the discretion to decide whether the patient received more than once CAR T-cell therapy.This study intends to include CEA+ patients with locally advanced and/or metastatic solid tumors.They will take the anti-CEA-CAR-T cell transfusion after a screening period, mononuclear cell (PBMC) collection, bridging therapy if necessary, and lymphocyte clearance pretreatment period.

Conditions

Carcinoma

Keywords

CAR-T; solid tumor; Cell therapy; CEA

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Dose-limiting toxicity

  21 days within anti-CEA-CAR-T cell infusion

Secondary Outcomes (1)

• Objective response rate

  4week,8week,3month,6month,9month and12month after the anti-CEA-CAR-T cell infusion

Study Arms (1)

Anti-CEA-CAR-T cell infusion

EXPERIMENTAL

Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10\^7 CAR-T cells/kg, 1×10\^7 CAR-T cells/kg, and 3×10\^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.The patients will receive lymphocyte clearance therapy with cyclophosphamide and fludarabine before the infusion.

Biological: Intravenous infusion anti-CEA-CAR-T cell

Interventions

Intravenous infusion anti-CEA-CAR-T cell BIOLOGICAL

Anti-CEA-CAR-T cell is administered as a single intravenous infusion. Follow-up infusions are based on the investigator's decision.The dose group to be infusion was 0.3×10\^7 CAR-T cells/kg, 1×10\^7 CAR-T cells/kg, and 3×10\^7 CAR-T cells/kg based on the 3+3 dose escalation principle. The infusion dose refers to the number of CAR-positive cells.

Also known as: cyclophosphamide, fludarabine

Anti-CEA-CAR-T cell infusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should understand and sign informed consent forms and voluntarily participate in clinical studies;
• Age≥ 18, \< 70 years old, gender is not limited;
• Locally advanced and/or metastatic solid tumors; Cytoplasmic and/or membranous high CEA expression in tumor tissue is required (expression intensity of 2+ and above on the area ≥50%) ;
• Histology-confirmed solid tumors (gastric cancer, colorectal cancer, esophageal cancer, small bowel cancer, pancreas adenocarcinoma and other digestive system tumors are predominant), conventional treatment is ineffective or Intolerability conventional treatment or lack of effective treatment;
• According to RECIST v 1.1, at least one measurable lesion with a maximum lesion diameter not exceeding 6 cm;
• Expected survival≥ 12 weeks;
• ECOG score≤ 2 ;
• Adequate hematological function ; have no performed blood transfusion or received cell growth factor within 7 days before screening hematological evaluation:
• Neutrophil ≥ 1.0×10\^9/L
• Hemoglobin≥ 80g/L
• Platelet ≥ 75×10\^9/L
• Lymphocytes ≥ 0.5×10\^9/L
• Adequate liver function: serum total bilirubin ≤1.5× ULN (excluding Gilbert's syndrome); AST and ALT≤2.5×ULN；( AST and ALT ≤5×ULN with liver metastasis)
• Adequate renal function: creatinine ≤1.5× ULN or endogenous creatinine clearance ≥50 mL/min;
• LVEF ≥ 50%;

You may not qualify if:

• Previously using any CAR-T cell products or other genetically modified T cell therapies;
• Patients who are waiting for organ transplantation or with a history of allogeneic stem cell or solid organ transplantation;
• Patients with acute or uncontrolled active infection, including but not limited to active tuberculosis;
• Patients with Hepatitis B infection (HBV surface antigen positive and/or hepatitis B core antibody positive and hepatitis B DNA \>10\^3 copies /mL) ; hepatitis C infection(hepatitis C antibodies positive) ; Syphilis infection (antibody positive), HIV infection (antibody positive);
• Patients with hyponatremia and/or hypokalemia, blood sodium \<125mmol/L and/or blood potassium\<3.5mmol/L (Sodium and/or potassium supplementation may be given before participating in the study to restore blood sodium and/or potassium above this level);
• Imaging results the proportion of liver replaced by tumor ≥50%;
• Patients who taken continuous systemic steroids within 14 days before apheresis or within 72 hours before cell therapy (prednisone\> 5 mg/day or equivalent dose of other hormones), excepting for those who use inhaled Steroid hormones;
• Systemic sexualization is accepted 2 weeks before apheresis or 5 half-lives (whichever is shorter). Toxicity to previous antineoplastic therapy has not recovered (based on CTCAE version 5.0 assessment); excepting for alopecia, pigmentation and other tolerable events judged by the investigator or permitted laboratory abnormalities according to the protocol;
• Antibody therapy within 4 weeks before apheresis and preconditioning;
• Anti-PD-1/PD-L1 monoclonal antibody therapy within 4 weeks before apheresis and preconditioning;
• Immunostimulation or immunosuppressive therapy within 28 days prior to apheresis;
• Radiotherapy within 28 days prior to apheresis, except limited local palliative radiotherapy;
• Patients with other malignant tumors within the past 5 years or at the present (except for basal cell carcinoma of the skin, breast/cervix Carcinoma in situ and other malignant tumors that have not been treated in the past five years have been effectively controlled);
• Patients with active ulcers or active gastrointestinal bleeding that are difficult to control;
• Patients with previous medical history of central nervous system (CNS) primary or metastatic tumors including meningeal metastases, unless previously treated for brain metastases, who are currently asymptomatic, and do not need steroid or enzyme-inducing antiepileptic drug treatment within 14 days before screening;

Sponsors & Collaborators

• China Medical University, China: lead
• Shanghai First Song Therapeutics Co., Ltd: collaborator

Study Sites (1)

The First Affiliated Hospital of China Medical Univeristy

Shenyang, Liaoning, 110001, China

RECRUITING

MeSH Terms

Conditions

Carcinoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Zhenning Wang, doctor

  The First Affiliated Hospital of China Medical Univeristy

  PRINCIPAL INVESTIGATOR

• Funan Liu, doctor

  The First Affiliated Hospital of China Medical Univeristy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhui Song, bachelor

CONTACT

024-83281137; 593900927@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: August 28, 2023
• Study Start: October 23, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 21, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)