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:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • ORG STUDY ID: 16-040
  • NCT ID: NCT02792114

Conditions

  • Breast Cancer
  • Metastatic HER2-negative Breast

Interventions

DrugSynonymsArms
CyclophosphamideT-cell infusion
Mesothelin-targeted T cellsT-cell infusion
AP1903T-cell infusion

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.

Trial Arms

NameTypeDescriptionInterventions
T-cell infusionExperimentalA 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 minimum of 48 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
  • Mesothelin-targeted T cells
  • 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 (pathology from
             outside institutions is acceptable for the screening phase of the protocol) 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 (>1.0 nM/L)

          -  Presence of measurable 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 1 month before
             the T-cell infusion.

             *Chemotherapy must have been completed at least 7 days prior to 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) <5x ULN

               -  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 1 month 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 of T-cell infusion
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated does (MTD)
Time Frame:2 years
Safety Issue:
Description:We have designed the dose-escalation using a standard 3+3 design. In this design, patients will be treated in sequential groups of 3 to 6 patients per T cell dose. With 4 dose levels, the projected trial size for this study is a minimum of 4 and a maximum of 24 patients.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • T-Cell
  • Chimeric antigen receptor (CAR)
  • CAR T cells
  • Triple-negative breast cancer
  • Immunotherapy T-cell therapy
  • 16-040
  • immunotherapy
  • CAR

Last Updated

August 13, 2021