The purpose of this study is to see whether a combination of two different drugs -
pembrolizumab and capecitabine - is safe, and if it might be effective in treating triple
negative and hormone-refractory breast cancer. Pembrolizumab is a type of drug that contains
an antibody. Antibodies are the part of your immune system that finds things that don't
belong in your body, such as bacteria or viruses. The antibody in pembrolizumab finds and
blocks a protein, which allows your immune system to target and destroy cancer cells.
Pembrolizumab is Food and Drug Administration (FDA) approved for other types of cancer. It is
not approved for breast cancer, meaning that it is an "experimental" or "investigational"
treatment. Capecitabine is a type of chemotherapy pill that is a standard treatment and
FDA-approved for breast cancer. It stops the cancer cells from being able to multiply.
Inclusion Criteria:
- Patients must have histologically-confirmed unresectable, locally advanced or
metastatic breast cancer that meets one of the following:
- Triple negative, defined as estrogen receptor (ER) negative, progesterone
receptor (PR) negative, human epidermal growth factor receptor 2 (HER2) negative;
HER2 negative defined as immunohistochemistry (IHC) 0 or 1+ or fluorescence in
situ hybridization (FISH) negative
- Hormone-refractory breast cancer which denotes progression to endocrine therapy
(e.g., tamoxifen, aromatase inhibitors, fulvestrant) unless contraindicated
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
2
- Patients must have a life expectancy of >= 90 days
- Patients must have baseline laboratory tests within the following parameters at least
4 weeks (28 days) prior to registration:
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl) >= 60
mL/min for subject with creatinine levels > 1.5 x institutional ULN
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total
bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN OR =< 5 x ULN for subjects with liver metastases
- Albumin >= 2.5 mg/dL
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants
- Females of child-bearing potential (FOCBP) must have a negative serum or urine
pregnancy test within 7 days prior to registration and must be at least within 3 days
prior to first dose of study drug. If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required
- (Note: a FOCBP is any woman [regardless of sexual orientation, having undergone a
tubal ligation, or remaining celibate by choice] who meets the following
criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and therefore
has not been naturally postmenopausal for > 12 months)
- Female subjects of childbearing potential (FOCBP) must be willing to use an adequate
method of contraception; contraception must be used for the course of the study
through 120 days after the last dose of study medication
- Note: abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject
- Male subjects of childbearing potential must agree to use an adequate method of
contraception; contraception must be used starting with the first dose of study
therapy through 120 days after the last dose of study therapy
- Note: abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject
- Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration on study
- Patients must be willing and able to comply with scheduled visits, treatment plan and
laboratory tests
- Patient must be able to swallow and retain oral medication
Exclusion Criteria:
- Patients with documented HER2-positive metastatic disease are not eligible, even if
their primary breast cancer was HER2-negative
- Patients who have received prior anti-cancer therapy (e.g., biologic or other targeted
therapy, chemotherapy) within 2 weeks prior to registration; hormone therapy is
permitted until registration
- Note: patients who received prior anti-PD-1, PD-L1 or PD-L2 agents are still
eligible
- Patients who have not recovered from adverse events to grade 1 severity or lower due
to agents administered more than 2 weeks earlier than registration, are not eligible,
except for stable sensory neuropathy (=< grade 2) and alopecia
- Patients who have received radiotherapy =< 4 weeks prior to registration, with the
exception of palliative radiotherapy, who have not recovered from side effects of such
therapy to baseline or grade =< 1 are not eligible for participation
- Patients with central nervous system (CNS) involvement may participate if they meet
all the following criteria:
- At least 4 weeks from prior therapy completion (including radiation and/or
surgery) to starting the study treatment,
- Clinically stable with respect to the CNS tumor at the time of screening
- Patients who have undergone major surgery =< 4 weeks prior to registration or have not
recovered from side effects of such procedure are not eligible for participation
- Patients may not be receiving any other investigational agents
- Patients who have a history of allergic reactions or hypersensitivity reactions
attributed to compounds of similar chemical or biologic composition to pembrolizumab
and/or humanized antibodies are not eligible
- Known hypersensitivity to capecitabine, fluorouracil, or any component of the
formulation
- Note: prior capecitabine is permitted
- History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis or glomerulonephritis
- Patients with history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone may be eligible for this study
- Patients with controlled type I diabetes mellitus on a stable dose of insulin
regimen for more than a month may be eligible for this study
- Patients who have evidence of active, noninfectious pneumonitis or have a history of
severe pneumonitis that required treatment with steroids are not eligible for this
study; (Note: replacement physiologic dose of steroids [prednisone 10 mg daily or
equivalent] are allowed)
- Patients who have an uncontrolled intercurrent illness including, but not limited to
any of the following, are not eligible:
- Hypertension that is not controlled on medication (defined as >= 140/100 at rest,
average of 3 consecutive readings)
- Ongoing or active infection requiring systemic treatment
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Clinically significant electrocardiogram (ECG) abnormality, e.g., a repeated
demonstration of a QTc interval > 500 ms
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Known positive test for human immunodeficiency virus (HIV)
- 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)
- Active tuberculosis
- Prior allogeneic bone marrow transplantation or solid organ transplant
- Administration of a live, attenuated vaccine within 4 weeks before starting the
study treatment or anticipation that a live attenuated vaccine will be required
during the study
- Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or study
endpoints
- Female patients who are pregnant or nursing (lactating) are not eligible
- Patients exhibiting any other condition that would, in the Investigator's judgment,
preclude patient's participation in the clinical study due to safety concerns or
compliance with clinical study procedures are not eligible for participation; this
might include, but is not limited to, infection/inflammation, intestinal obstruction,
and/or social/psychological complications
- Patients with impaired gastrointestinal (GI) function or GI disease that may
significantly alter absorption of oral capecitabine (e.g. ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
resection) are not eligible for participation
- Patients with a history of another malignancy that progressed or required treatment
within 5 years prior to registration are not eligible for participation; Note: the
exceptions to this include non-melanoma skin cancer or excised carcinoma in situ of
the cervix
