Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis
Condition: Breast Carcinoma Metastatic in the Brain; Estrogen Receptor Negative; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer
MeSH terms: Carcinoma; Breast Neoplasms; Brain Neoplasms
Intervention: Cognitive Assessment; Palbociclib; Quality-of-Life Assessment; Trastuzumab
Intervention description: Ancillary studies; Given PO; Ancillary studies; Given IV
Intervention MeSH terms: Antineoplastic Agents, Immunological; Trastuzumab; Palbociclib; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate if the study drug palbociclib has anti-tumor
      activity against the breast cancer that has spread to the brain and also to determine the
      overall radiographic response rate in the CNS. Palbociclib is an anti-cancer medication that
      has been shown to stop cancer cells from growing. It has been approved in hormone positive
      breast cancer, along with other hormone therapies and has been found to be effective. The
      preclinical studies suggest that the drug may also have activity in other types of breast
      cancer, such as HER2 positive breast cancer. The purpose of this study is to see if the study
      drug is effective in patients with brain metastasis, who have HER2-positive breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed HER2-positive metastatic breast cancer (estrogen and
             progesterone receptor 0%, HER-2 3+ by immunohistochemistry (IHC); if IHC score of 2,
             fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less
             than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not
             required to have pathologic confirmation

          -  Patients should not have received > 2 lines of chemotherapy for metastatic disease

          -  Patients must have a life expectancy of at least 12 weeks at the time of registration

          -  Eastern Cooperative Oncology Group (ECOG) performance status >= 2

          -  Measurable disease in the brain, defined as at least 1 lesion measuring >= 5 mm on
             imaging at the time of registration

          -  If patients are on corticosteroids, they must have been on a stable or decreasing dose
             >= 5 days prior to obtaining their baseline gadolinium (Gd)-magnetic resonance imaging
             (MRI) of brain; this MRI is to be obtained within 28 days of registration; NOTE: If
             patient needs escalation of steroids prior to therapy, or are on unstable doses of
             steroids they are not eligible

          -  Patients who underwent neurosurgery (NSGY) or stereotactic radiosurgery (SRS) to a
             brain lesion must have a new measureable lesion; NOTE: SRS may be done to a lesion
             that will not be used for response evaluation and should be done > 2 weeks prior to
             registration; any NSGY procedure must have been completed > 3 weeks prior to
             registration

          -  Patients must not have received systemic therapy within 2 weeks of initiating
             palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain on
             the drug; no break or washout period required; however, lapatinib,
             ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out period
             of 2 weeks is required

          -  Patients must exhibit adequate bone marrow, liver, and renal function, within 14 days
             prior to registration, defined as:

               -  Absolute neutrophil count (ANC) >= 1,000/mm^3 (growth factor support is
                  permitted)

               -  Platelets >= 100,000/mm^3 (may be reached by transfusion)

               -  Hemoglobin >= 10 gm/dl (may be reached by transfusion)

               -  Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) <
                  3 x upper limit of normal (ULN) (or < 5 x ULN in case of liver metastasis)

               -  Bilirubin < 3 x ULN (or < 5 x ULN in case of liver metastasis)

               -  Creatinine < 1.5 x ULN

          -  Females of child-bearing potential (FOCBP) and males must agree to use adequate
             contraception prior to study entry, for the duration of study participation, and for 2
             weeks following completion of therapy; should a female patient become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately; likewise, if the female partner of a male patient
             becomes pregnant while participating in this study, he should inform his treating
             physician immediately; 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 patients must have a negative urine pregnancy test within 7 days prior to
             registration; if urine test is positive, it should be followed by serum pregnancy test

          -  Patients must sign an informed consent prior to registration and before undergoing any
             study-specific procedures indicating that they are aware of the investigational nature
             of this study

          -  Patient must have the ability to swallow and retain oral medication

          -  Patient must have the ability to comply with all study requirements

        Exclusion Criteria:

          -  Any uncontrolled neurological symptom attributed to CNS metastasis

          -  Brain metastasis must not be impending herniation or other significant vasogenic edema
             requiring increasing steroid doses; lesions must not have frank hemorrhage

          -  Patients with leptomeningeal disease are not eligible for participation

          -  Any significant medical illnesses or infection that, in the investigator's opinion,
             cannot be adequately controlled with appropriate therapy or would compromise the
             patient's ability to tolerate this therapy are not eligible for participation

          -  Known human immunodeficiency virus (HIV) positive status

          -  Known active hepatitis B and/or C

          -  Previous treatment with palbociclib

          -  Patients who have a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to palbociclib are not eligible; AND/OR patients who
             have had prior exposure to compounds of similar chemical or biologic composition to
             palbociclib are not eligible hypersensitivity to any component of palbociclib are not
             eligible for participation

          -  Patients being treated with any other experimental agents/clinical trials are not
             eligible for participation; if the patient is on any investigational agent, a wash-out
             period of minimum 2 weeks prior to registration is mandatory for the patient to be
             eligible for the study

          -  Patients who are on any prohibited medication; a wash-out period of minimum 2 weeks
             prior to registration is mandatory for the patient to be eligible for the study

          -  Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that
             severely affects the absorption of study drugs, major resection of the stomach or
             small bowel, or gastric bypass procedure

          -  Patients who have an uncontrolled intercurrent illness including, but not limited to
             any of the following, are not eligible:

               -  Ongoing or active infection requiring systemic treatment

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia: except atrial fibrillation (AF) and supraventricular
                  tachycardia (SVT) that are controlled by medication

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  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 are not eligible