Pembrolizumab and Tamoxifen With or Without Vorinostat for the Treatment of Estrogen Receptor Positive Breast Cancer
Condition: Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8
MeSH terms: Breast Neoplasms
Intervention: Pembrolizumab; Tamoxifen; Vorinostat
Intervention description: Given IV; Given PO; Given PO
Intervention MeSH terms: Tamoxifen; Pembrolizumab; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab and tamoxifen with or without vorinostat
      work for the treatment of estrogen receptor positive breast cancer. Immunotherapy with
      monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Estrogen can
      cause the growth of breast cancer cells. Hormone therapy with tamoxifen may may fight breast
      cancer by blocking the use of estrogen by the tumor cells. Vorinostat may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. This trial is being done
      to find a drug combination to better control estrogen receptor positive breast cancer and
      reduce the number of pills taken.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pre and postmenopausal women or men with stage IV ER+ breast cancer histological or
             cytological confirmation

          -  > 10% expression of PD-1/Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dual
             staining in Cluster of differentiation 8 (CD8) cells in tumor or blood or >5%
             expression of PD-1/CTLA-4 dual staining in CD4 in blood (only).

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1

          -  Understand and voluntarily sign an informed consent prior to any study-related
             assessments or procedures are conducted and are able to adhere to the study visit
             schedule and other protocol requirements

          -  Consent to paired tumor biopsy

          -  Measurable tumor by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

          -  Per Good Clinical Practice, any toxicity related to prior therapies that, in the
             opinion of the investigator, would potentially be worsened with anti-PD1 therapy
             should be resolved to less than grade 1

          -  Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

          -  Hemoglobin (Hgb) >= 9 g/dL (may transfuse if clinically indicated)

          -  Platelets (plt) >= 100 x 10^9/L

          -  Potassium within normal range, or correctable with supplements

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
             limit normal (ULN) or =< 5.0 x ULN if liver tumor is present

          -  Serum total bilirubin =< 1.5 x ULN

          -  Serum creatinine =< 1.5 x ULN, or 24-hr clearance >= 60 ml/min

          -  Females of childbearing potential (defined as sexually mature women who):

               -  Has not undergone a hysterectomy (the surgical removal of the uterus) or
                  bilateral oophorectomy (the surgical removal of both ovaries) or,

               -  Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
                  has had menses at any time during the preceding 24 consecutive months) must have

                    -  Negative serum pregnancy test within 14 days before starting study treatment
                       in females of childbearing potential (FCBP) and willingness to adhere to
                       acceptable forms or birth control (a physician-approved contraceptive method
                       (oral, injectable, or implantable hormonal contraceptive; tubal ligation;
                       intra-uterine device; barrier contraceptive with spermicide; or vasectomized
                       partner)

          -  All female and male participants must agree to use approved contraception during the
             treatment period and for at least 18 weeks after the last dose of study treatment and
             refrain from donating sperm during this period

        Exclusion Criteria:

          -  Prior treatment with pembrolizumab or other PD-(L)1

          -  Any significant medical condition, laboratory abnormalities, which places the subject
             at unacceptable risk if he/she were to participate in the study

          -  Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
             steroids or current pneumonitis/ interstitial lung disease

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or
             hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) [qualitative] is
             detected)

          -  Has a history of hepatitis B virus (HBV)

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Symptomatic central nervous system metastases. Subjects with brain metastases that
             have been previously treated and are stable for 6 weeks are allowed

          -  Persistent diarrhea or malabsorption >= National Cancer Institute (NCI) Common
             Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management

          -  Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA)
             class 3 or 4 congestive heart failure

          -  Prior systemic cancer-directed treatments or investigational modalities =< 5
             half-lives or 4 weeks, whichever is shorter, prior to starting study drug or who have
             not recovered from side effects of such therapy (except alopecia)

          -  Active autoimmune disease except for vitiligo or hypothyroidism

          -  Active and ongoing steroid use, except for non-systemically absorbed treatments (such
             as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary
             disease (COPD), allergic rhinitis)

          -  Major surgery =< 2 weeks prior to starting a study drug or who have not recovered from
             side effects of such therapy

          -  Pregnant or breastfeeding

          -  Known human immunodeficiency virus (HIV) infection

          -  Known history of tuberculosis

          -  Known allergic reaction or intolerability to tamoxifen

          -  Patients with prior history of deep vein thrombosis (DVT)s must be on therapeutic or
             preventive anticoagulation