A Clinical Study of CEA-targeted CAR-T in the Treatment of CEA-positive Advanced Malignant Solid Tumors

Sponsor
Weijia Fang, MD (Other)
Overall Status
Recruiting
CT.gov ID
NCT05396300
Collaborator
Chongqing Precision Biotech Co., Ltd (Industry)
60
1
2
35.7
1.7

Study Details

Study Description

Brief Summary

This is a phase I clinical study to evaluate the safety and tolerability of CAR-T in patients with CEA-positive advanced malignant solid tumors, and to obtain the maximum tolerated dose of CAR-T and phase II Recommended dose.

Condition or Disease Intervention/Treatment Phase
  • Biological: CEA CAR-T cells
Phase 1

Detailed Description

This is a single-center, double-arm, open-label study. The study plans to set up 2 groups,Intravenous infusion group have 3 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 9-18 subjects with CEA-positive advanced malignant solid tumors.Intraperitoneal injection group have 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12-24 subjects with CEA-positive advanced malignant solid tumors.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Clinical Study of Anti-CEA CAR-T Therapy in the Treatment of CEA-positive Advanced Malignant Solid Tumors
Actual Study Start Date :
May 25, 2022
Anticipated Primary Completion Date :
May 15, 2024
Anticipated Study Completion Date :
May 15, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intravenous of CEA-targeted CAR-T

Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg

Biological: CEA CAR-T cells
Administration method: intravenous infusion or intraperitoneal injection; Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

Experimental: intraperitoneal injection of CEA-targeted CAR-T

Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg

Biological: CEA CAR-T cells
Administration method: intravenous infusion or intraperitoneal injection; Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

Outcome Measures

Primary Outcome Measures

  1. Incidence of Adverse events after CEA-CAR-T cells infusion [Safety and Tolerability] [28 days]

    Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

  2. Obtain the maximum tolerated dose of CEA-CAR-T cells[Safety and Tolerability] [28 days]

    Dose-limiting toxicity after cell infusion

Secondary Outcome Measures

  1. Disease control rate of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness] [3 months]

    Disease control rate: including CR, PR and SD

  2. Changes in serum tumor markers of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness] [3 months]

    Changes in serum tumor markers:CEA、 CA199、 CA125

  3. AUCS of CEA-CAR-T cells [Cell dynamics] [1 years]

    AUCS is defined as the area under the curve in 28 days and 90 days

  4. CMAX of CEA-CAR-T cells [Cell dynamics] [1 years]

    CMAX is defined as the highest concentration of CEA-CAR-T cells expanded in peripheral blood

  5. TMAX of CEA-CAR-T cells[Cell dynamics] [1 years]

    TMAX is defined as the time to reach the highest concentration

  6. Pharmacodynamics of CEA-CAR-T cells[Cell dynamics] [1 years]

    The content of free CEA in peripheral blood at each time point measured by Chemiluminescence immunoassay

Other Outcome Measures

  1. Objective response rate (ORR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness] [1 years]

    Objective response rate includes:CR、PR

  2. Duration of Response (DOR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness] [1 years]

    DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause

  3. Progress-free survival(PFS) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness] [1 years]

    PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression.

  4. Overall survival(OS)of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness] [1 years]

    OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause

  5. Proportion of tumor cells in tumor tissue of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies [1 years]

    The rate of tumor cell in tumor tissue will be measured by biopsy and immunohistochemistry

  6. CEA expression level of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies [1 years]

    The CEA expression in tumor tissue will be measured by biopsy and immunohistochemistry

  7. Changes in the number of tumor-infiltrating immune cells of CEA- CAR-T treatment in patients with CEA-positive [1 years]

    the number of tumor-infiltrating immune cells will be measured by biopsy and immunohistochemistry

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Age ≥18 years old, male or female;

  2. Advanced, metastatic or recurrent malignant tumors diagnosed by histology or pathology, mainly colorectal cancer, esophageal cancer, gastric cancer, and pancreatic cancer;

  3. After receiving at least second-line standard treatment and failing (disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of effective treatment methods;

  4. Immunohistochemical staining of tumor samples within 3 months confirmed that the tumor was CEA positive (clear membrane staining, positive rate ≥ 10%); the patient's serum CEA should exceed 10ug/L.

  5. At least one assessable lesion according to RECIST 1.1 criteria;

  6. ECOG score 0-2 points;

  7. No serious mental disorder;

  8. Unless otherwise specified, the function of the vital organs of the subject shall meet the following conditions:

  9. Blood routine: white blood cells>2.0×109/L, neutrophils>0.8×109/L, lymphocytes cells>0.5×109/L, platelets>50×109/L, hemoglobin>90g/L;

  10. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;

  11. Renal function: serum creatinine≤2.0×ULN;

  12. Liver function: ALT and AST ≤3.0×ULN (for those with liver tumor infiltration, it can be relaxed to≤5.0×ULN);

  13. Total bilirubin≤2.0×ULN;

  14. Oxygen saturation > 92% in non-oxygen state.

  15. Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;

  16. Subjects agree to use reliable and effective contraceptive methods for contraception within 1 year after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);

  17. The patients themselves or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.

Exclusion Criteria:
  1. CNS metastases or meningeal metastases with clinical symptoms at the time of screening, or there is other evidence that the patient's central nervous system metastases or meningeal metastases have not been controlled, and are judged by the investigator to be unsuitable for inclusion;

  2. Participated in other clinical studies within 1 month before screening;

  3. vaccinated with live attenuated vaccine within 4 weeks before screening;

  4. Received the following anti-tumor treatments before screening: Received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);

  5. Active infection or uncontrollable infection requiring systemic treatment;

  6. Patients with intestinal obstruction, active gastrointestinal bleeding, or a history of gastrointestinal bleeding within 3 months;

  7. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor therapy has not improved to the baseline level or ≤ grade 1;

  8. Suffering from any of the following heart diseases:

  9. New York Heart Association (NYHA) stage III or IV congestive heart failure;

  10. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;

  11. Clinically significant ventricular arrhythmia, or history of syncope of unknown origin (caused by vasovagal except those caused by neurosis or dehydration);

  12. History of severe non-ischemic cardiomyopathy;

  13. Patients with active autoimmune disease, or other patients requiring long-term immunosuppressive therapy;

  14. Suffering from other uncured malignant tumors in the past 3 years or at the same time, except cervical carcinoma in situ and basal cell carcinoma of the skin;

  15. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive;

  16. Women who are pregnant or breastfeeding;

  17. Other investigators deem it unsuitable to participate in the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 First affiliated hospital, Zhejiang University Hangzhou Zhejiang China 310006

Sponsors and Collaborators

  • Weijia Fang, MD
  • Chongqing Precision Biotech Co., Ltd

Investigators

  • Principal Investigator: Weijia Fang, M.D, The First Affiliated Hospital, Zhejiang University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Weijia Fang, MD, MD, Zhejiang University
ClinicalTrials.gov Identifier:
NCT05396300
Other Study ID Numbers:
  • PBC039
First Posted:
May 31, 2022
Last Update Posted:
Jun 2, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Weijia Fang, MD, MD, Zhejiang University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 2, 2022