Clinical trial NCT02792114: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Metastatic HER2-negative Breast
Keywords: T-Cell
Chimeric antigen receptor (CAR)
CAR T cells
Triple-negative breast cancer
Immunotherapy T-cell therapy
16-040
immunotherapy
CAR
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2016-06-07
Enrollment: 186
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Maximum tolerated does (MTD)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center (Consent and follow-up only)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Consent and follow-up only)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Consent and follow-up only)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center at Commack (Consent and follow-up only)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Consent and follow-up only)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Consent and Follow-Up only)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Shanu Modi, MD
role: PRINCIPAL_INVESTIGATOR
References: