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EpCAM CAR-T for Treatment of Nasopharyngeal Carcinoma and Breast Cancer

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ClinicalTrials.gov Identifier: NCT02915445
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : September 27, 2016
Sponsor:
Information provided by (Responsible Party):
Wei Wang, Sichuan University

Brief Summary:
This study is for patients that have nasopharyngeal carcinoma or breast cancer. 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 3rd 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 or breast cancer.

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M) Breast Cancer Recurrent Biological: CAR-T cells recognizing EpCAM Phase 1

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  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: T Cells Armed With Chimeric Antigen Receptor Recognizing EpCAM for Patients With Nasopharyngeal Carcinoma and Breast Cancer
Study Start Date : July 2016
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: CAR-T cells recognizing EpCAM
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: CAR-T cells recognizing EpCAM
Patients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed.




Primary Outcome Measures :
  1. 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 and breast cancer expressing EpCAM.


Secondary Outcome Measures :
  1. Response rate of participants treated with EpCAM CAR-T cells assessed by RECIST v1.1 [ Time Frame: 6-12 weeks 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 nasopharyngeal and breast cancer.

  2. Persistence of EpCAM CAR-T cells and correlation with the Response rate [ Time Frame: 6-12 weeks post CAR-T infusion ]
  3. Persistence of EpCAM positive circulating tumor cells [ Time Frame: 6 weeks post CAR-T infusion ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion criteria at the time of procurement:

  • Recurrent or refractory nasopharyngeal carcinoma and breast cancer.
  • 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 and breast cancer 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915445


Contacts
Contact: Wei Wang, Ph.D +86 028 85164063 weiwang@scu.edu.cn

Locations
China, Sichuan
West China Hospital, Sichuan University Recruiting
Chengdu, Sichuan, China, 610041
Contact: Nianyong Chen, MD    +86 028 85422952    nchenyy@yahoo.com   
Principal Investigator: Nianyong Cheng, MD         
Sponsors and Collaborators
Sichuan University
Investigators
Principal Investigator: Wei Wang, Ph.D State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University

Publications:

Responsible Party: Wei Wang, Dr, Sichuan University
ClinicalTrials.gov Identifier: NCT02915445     History of Changes
Other Study ID Numbers: SKLB-083
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: September 27, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Wei Wang, Sichuan University:
EpCAM CAR-T, solid tumors, cancer immunotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Nasopharyngeal Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases