We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
ClinicalTrials.gov Menu

T-Cell Therapy for Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02792114
Recruitment Status : Active, not recruiting
First Posted : June 7, 2016
Last Update Posted : March 24, 2023
United States Department of Defense
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic HER2-negative Breast Drug: Cyclophosphamide Biological: Mesothelin-targeted T cells Drug: AP1903 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 186 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 2016
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: T-cell infusion
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 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.
Drug: Cyclophosphamide
Biological: Mesothelin-targeted T cells
Drug: AP1903

Primary Outcome Measures :
  1. Maximum tolerated does (MTD) [ Time Frame: 2 years ]
    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

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): NCT02792114

Layout table for location information
United States, New Jersey
Memoral Sloan Kettering Cancer Center (Consent and follow-up only)
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth (Consent and follow-up only)
Middletown, New Jersey, United States, 07748
Memorial Sloan Kettering Bergen (Consent and follow-up only)
Montvale, New Jersey, United States, 07645
United States, New York
Memorial Sloan Kettering Cancer Center at Commack (Consent and follow-up only)
Commack, New York, United States
Memorial Sloan Kettering Westchester (Consent and follow-up only)
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Nassau (Consent and Follow-Up only)
Uniondale, New York, United States, 11553
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
United States Department of Defense
Layout table for investigator information
Principal Investigator: Shanu Modi, MD Memorial Sloan Kettering Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02792114    
Other Study ID Numbers: 16-040
First Posted: June 7, 2016    Key Record Dates
Last Update Posted: March 24, 2023
Last Verified: March 2023
Keywords provided by Memorial Sloan Kettering Cancer Center:
Chimeric antigen receptor (CAR)
CAR T cells
Triple-negative breast cancer
Immunotherapy T-cell therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists