Clinical Trials /

T-Cell Therapy for Advanced Breast Cancer

NCT02792114

Description:

The purpose of this study is to test the safety of different doses of specially prepared T cells collected from the blood. The investigators want to find a safe dose of these modified T cells for patients who have metastatic HER2-negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

T-Cell Therapy for Advanced Breast Cancer

Title

  • Brief Title: T-Cell Therapy for Advanced Breast Cancer
  • Official Title: A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Mesothelin-Specific Chimeric Antigen Receptor-Positive T Cells in Patients With Metastatic Mesothelin-Expressing Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02792114

    ORG ID: 16-040

    Trial Conditions

    Breast Cancer

    Metastatic HER2-negative Breast

    Trial Interventions

    Drug Synonyms Arms
    Cyclophosphamide T-cell infusion
    AP1903 T-cell infusion

    Trial Purpose

    The purpose of this study is to test the safety of different doses of specially prepared T
    cells collected from the blood. The investigators want to find a safe dose of these modified
    T cells for patients who have metastatic Her2-negative breast cancer.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    T-cell infusion Experimental A single blood volume leukapheresis for harvesting of PBMCs will be performed, As the transduced T cells will be frozen, the timing of leukapheresis is not defined & can vary from patient to patient. Subsequently, a single dose of mesothelin-targeted T cells will be infused via intravenous catheter or central line (i.e., mediport). Patients will be monitored in the hospital and discharged home after a maximum of 72 hours. Patients will be monitored closely as outpatients for the next 2 months. Patients will be followed weekly as outpatients for the first 8 weeks after treatment. All patients will be hydrated intravenously, premedicated with acetaminophen & diphenhydramine, & administered cyclophosphamide at 1.5 g/m2 2 to 7 days (Day -7 to Day -2) before administration of mesothelin-targeted T cells. Cyclophosphamide, AP1903

    Eligibility Criteria

    Inclusion Criteria:

    - Patients aged 18 years with metastatic breast cancer

    - Karnofsky performance status 70%

    - Patients with breast cancer that is pathologically confirmed at MSKCC and defined by
    the following:

    - HER2 negative (in cases of mixed HER2 results, the most recent pathology results
    considered reflective of the active cancer will be considered)

    - Previously treated with at least 1 chemotherapy regimen for metastatic disease
    and documented progression

    - Expression of mesothelin must be confirmed by meeting 1 of the following criteria:

    - Mesothelin expression (>10% of the tumor expressing mesothelin) by IHC

    - Elevated serum SMRP levels (>0.4 nM/L)

    - Presence of measureable or evaluable disease

    - Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor), or radiotherapy
    must have been completed at least 14 days before administration of T-cells. Prior
    immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or
    CTL4-antagonist or similar agent) must have been completed more than 2 months before
    the T-cell infusion.

    *Chemotherapy must have been completed at least 7 days prior leukapheresis

    - Any major operation must have occurred at least 28 days before study enrollment.

    - All acute toxic effects of any previous radiotherapy, chemotherapy, or surgical
    procedures must have resolved to grade 1 or lower according to CTCAE

    - Lab requirements (hematology):

    - White blood cell (WBC) count 3000 cells/mm^3

    - Absolute neutrophil count 1500 neutrophils/mm^3

    - Platelet count 100,000 platelets/mm^3

    - Lab requirements (serum chemistry):

    - Bilirubin <1.5x upper limit of normal (ULN)

    - Serum alanine aminotransferase/serum aspartate aminotransferase (ALT/AST) <2.5x
    ULN; for patients with liver metastases, ALT/AST <5x ULN is acceptable.

    - Serum creatinine <1.5x ULN or Cr >1.5x ULN, but calculated clearances of >60

    - Negative screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV)
    antigen, and hepatitis C virus (HCV). If testing was performed during the previous 3
    months, there is no need to repeat testing, as long as documentation of results is
    provided to the study site. Subjects must receive counseling and sign a separate
    informed consent form for HIV testing.

    - Subjects and their partners with reproductive potential must agree to use an
    effective form of contraception during the period of drug administration and for 4
    weeks after completion of the last administration of the study drug. An effective
    form of contraception is defined as oral contraceptives plus 1 form of barrier or
    double-barrier method contraception (condom with spermicide or condom with
    diaphragm).

    - Subjects must be able to understand the potential risks and benefits of the study and
    must be able to read and provide written, informed consent for the study.

    - Availability of archival tumor tissues (FFPE tissue block or 10-15 unstained slides)

    Exclusion Criteria:

    - Untreated or active CNS metastases (progressing or requiring anticonvulsants or
    corticosteroids for symptomatic control); patients with a history of treated CNS
    metastases are eligible, provided that all of the following criteria are met:

    - Presence of measurable or evaluable disease outside of the CNS;

    - Radiographic demonstration of improvement upon completion of CNS- directed
    therapy and no evidence of interim progression between completion of
    CNS-directed therapy and the screening radiographic study;

    - Completion of radiotherapy 8 weeks prior to the screening radiographic study;

    - Discontinuation of corticosteroids and anticonvulsants 4 weeks prior to the
    screening radiographic study.

    - History of seizure disorder

    - Patients currently receiving treatment for concurrent active malignancy. Prior
    immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or
    CTL4-antagonist or similar agent) must have been completed more than 2 months prior
    to the T-cell infusion.

    - Autoimmune or antibody-mediated disease, including but not limited to systemic lupus
    erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and
    temporal arteritis (patients with a history of hypothyroidism will not be excluded)

    - Clinically significant cardiac disease (New York Heart Association class III/IV) or
    severe debilitating pulmonary disease

    - Pregnant or lactating women

    - Known active infection requiring antibiotics within 7 days of the start of treatment
    (Day 0)

    - A requirement for daily systemic corticosteroids for any reason or a requirement for
    other immunosuppressive or immunomodulatory agents. Topical, nasal, and inhaled
    steroids are permitted.

    - Administration of live, attenuated vaccine within 8 weeks before the start of
    treatment (Day 0) and throughout the study

    - Any other medical condition that, in the opinion of the PI, may interfere with a
    subject's participation in or compliance with the study

    - Participation in a therapeutic research study or receipt of an investigational drug
    within 30 days before the screening visit

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Maximum tolerated does (MTD)

    Secondary Outcome Measures

    Trial Keywords

    T-Cell

    Chimeric antigen receptor (CAR)

    CAR T cells

    Triple-negative breast cancer

    Immunotherapy T-cell therapy

    16-040