EpCAM CAR-T for Treatment of Advanced Solid Tumors

November 20, 2023 updated by: Wei Wang, Sichuan University

T Cells Armed With Chimeric Antigen Receptor Recognizing EpCAM for Patients With Advanced Solid Tumors

This study is for patients that have nasopharyngeal carcinoma, breast cancer, gastric cancer and other solid tumors. As epithelial cell adhesion molecule (EpCAM) is a well characterized molecule that is closely with poor prognosis and tumor metastasis and invasion. Many therapies targeting EpCAM have shown benefits for cancer patients. This study is to determine the safety of the engineered T cells armed with chimeric antigen receptor (CAR-T) recognizing EpCAM. At the same time, efficacy is to be evaluated by the criteria of RECIST. The EpCAM CAR-T were produced by lentiviral transduction of the novel 2nd generation of CAR genes. Different cohorts of patients receive EpCAM CAR-T with a dose-escalating manner. This study is to find the largest dose of EpCAM CAR-T, to learn what the adverse effects are and to find out whether this experimental intervention might help patients with nasopharyngeal carcinoma, breast cancer and other EpCAM positive solid tumors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

In this study, the original tumor tissue specimen should be stained to determine the expression levels of EpCAM. Only the patients having tumor with high expression levels will be included.

50-100ml blood with be drawn to get enough CD3 T cells at least 2x10^7. After separation, PBMC will be activated via antibodies of CD3 and CD28 and then transduced by lentivirus bearing the EpCAM CAR gene. Then the EpCAM CAR-T cells will proliferate up to 10-100 folds for infusion. The produced cells will be frozen or infused if available.

Included patients will be preconditioned by cyclophosphamide for lymphodepletion if the levels of white blood cells and lymphocytes are normal. Infusion of T cells, at least 1 day after lymphodepletion, is dose escalating and beginning at the lowest level. If the first level is proven to be safe, the next level will be proceeded. Once severe side effects were observed, the dose will be lowered or the dose will be stopped.

During infusion, patients will be taken care of by cardiogram monitor. Blood drawing will be taken before infusion, at 4h after infusion and on day 4, 7, 14, 30, 60, 90, 120, 150, 180 to determine the presence of CAR-T cells. At the same time, cytokines including IL-6, TNF-alpha and IFN-gamma and C-reactive protein levels will be determined. Routine imaging studies will be proceeded.

To see whether there are long-term side effects of this therapy, patients received CAR-T cells will be followed up to at least 15 years.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital, Sichuan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Inclusion criteria at the time of procurement:

  • Recurrent or refractory nasopharyngeal carcinoma and breast cancer and other solid tumors.
  • Karnofsky score of greater than or equal to 60.
  • Informed consent explained to, understood by and signed by subject/guardian. -
  • Subject/guardian given copy of informed consent

Treatment Inclusion criteria:

  • Recurrent or refractory EpCAM-positive nasopharyngeal carcinoma, breast cancer, gastric cancer and other epithelial tumors determined by Immunohistochemistry (IHC) or RT-PCR. EpCAM expression in tumors on IHC should be greater than or equal to grade 2 and greater than or equal to 2+ intensity score. Wherein grades are defines as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100% of cell staining for EpCAM and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity.
  • Age ≥ 18 years
  • Life expectancy ≥ 6 weeks
  • Karnofsky score ≥ 60
  • Bilirubin less than or equal to 3x normal, AST less than or equal to 5x normal,
  • ALT less than or equal to 5x, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 8.0
  • Pulse oximetry of greater than or equal to 90% on room air.
  • Sexually active subjects must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion. The male partner should use a condom.
  • Available autologous transduced T lymphocytes with greater than or equal to 20% expression of EpCAM CAR determined by flow-cytometry and killing of EpCAM-positive targets greater than or equal to 20% in cytotoxicity assay.
  • Subjects should have been off other investigational antineoplastic therapy for two weeks prior to entry in this study.
  • Cyclophosphamide will be allowed 72 hours preinfusion.
  • Dexamethasone up to a total dose of 2 mg per day will be allowed if medically indicated.
  • Informed consent explained to, understood by and signed by research subjects/guardian.
  • Subject/guardian given copy of informed consent.

Exclusion Criteria:

Exclusion Criteria at the time of procurement:

  • Known HIV positivity.

Treatment Exclusion Criteria:

  • Severe intercurrent infection.
  • Known HIV positivity.
  • Pregnant or lactating.
  • History of hypersensitivity reactions to murine protein-containing products.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EpCAM CAR-T cells
Autologous T cells from patient are engineered to expressing a special chimeric antigen receptor to recognizing EpCAM by lentiviral vector. The engineered T cells were then endowed cytotoxicity to the tumor cells and hold the potential to inhibit the advance of tumors.
Biological: EpCAM CAR-T cells
Patients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events/dose limiting toxicity as assessed by CTCAE v4.0
Time Frame: 6 weeks after infusion
Determine the largest dose of EpCAM CAR-T cells for patients with nasopharyngeal carcinoma, breast cancer and other tumors expressing EpCAM.
6 weeks after infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate of participants treated with EpCAM CAR-T cells assessed by RECIST v1.1
Time Frame: 24 months after infusion of the CAR-T cells
Determine whether there is therapeutic efficacies of the safe dose infusion of EpCAM CAR-T cells for patients with solid tumors.
24 months after infusion of the CAR-T cells
Persistence of EpCAM CAR-T cells and correlation with the Response rate
Time Frame: 24 months post CAR-T infusion
24 months post CAR-T infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sichuan University

Investigators

  • Principal Investigator: Wei Wang, Ph.D, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2016

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

September 21, 2016

First Submitted That Met QC Criteria

September 23, 2016

First Posted (Estimated)

September 27, 2016

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SKLB-083

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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