Tivantinib in Treating Patients With Recurrent or Metastatic Breast Cancer
Condition: Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma
MeSH terms: Carcinoma; Breast Neoplasms
Intervention: Laboratory Biomarker Analysis; Tivantinib
Intervention description: Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well tivantinib works in treating patients with recurrent or
      metastatic breast cancer. Tivantinib may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed invasive breast
             cancer, with recurrent or metastatic disease; participants without pathologic or
             cytologic confirmation of metastatic disease should have unequivocal evidence of
             metastasis from physical examination or radiologic evaluation

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography (CT) scan

          -  Participants must have recent evidence of progressive disease

               -  Participants must have received 1-3 prior chemotherapeutic regimens for
                  metastatic breast cancer and must have been off treatment with chemotherapy for
                  at least 14 days before enrollment in the study

          -  Participants must have discontinued all biologic therapy (including vaccines) at least
             14 days before enrollment in the study

          -  Participants must have discontinued any investigational therapy at least 14 days
             before enrollment in the study

          -  Participants may have received prior radiation therapy in either the metastatic or
             early-stage setting

               -  Radiation therapy must be completed at least 14 days before enrollment in the
                  study

               -  Participant must not have received radiation to > 25% of his or her bone marrow
                  within 30 days of starting study treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Hemoglobin >= 9.0 g/dL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
             =< 2.5 times institutional ULN; for participants with documented liver metastases,
             AST/ALT =< 5.0 times ULN

          -  Serum creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for
             participants with creatinine levels above institutional normal

          -  Either the primary tumor and/or the metastasis must be triple-negative; the invasive
             tumor must be hormone-receptor poor, defined as estrogen-receptor negative (ER-) and
             progesterone-receptor negative (PR-), or staining < 10% by immunohistochemistry (IHC)

               -  Human epidermal growth factor receptor 2 (HER2) status: the invasive tumor must
                  be HER2-negative, defined as 0 or 1+ by IHC, or FISH < 2.0

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) during the study and for 90
             days after the last investigational drug dose received

          -  Female subjects of childbearing potential must have a negative serum pregnancy test
             within 21 days of cycle 1 day 1

          -  Participants on bisphosphonates may continue receiving bisphosphonate therapy during
             study treatment; bisphosphonate therapy may also be initiated on study treatment if
             needed

          -  Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Participants who have received chemotherapy, biologic, investigational, or
             radiotherapy within 14 days prior to entering the study

          -  Participants who are receiving any other investigational agents

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms

               -  Participants with a history of treated central nervous system (CNS) metastases
                  are eligible

                    -  Treated brain metastases are defined as those having no evidence of
                       progression or hemorrhage for >= 2 months after treatment, and no ongoing
                       requirement for corticosteroids, as ascertained by clinical examination and
                       brain imaging (magnetic resonance imaging or computed tomography [CT] scan)
                       during the screening period

                    -  Treatment for brain metastases may include whole-brain radiotherapy,
                       radiosurgery, or a combination as deemed appropriate by the treating
                       physician

               -  Participants may be taking anti-convulsant medications, which must be
                  non-enzyme-inducing anti-epileptic drugs

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ARQ 197

          -  History of congestive heart failure defined as Class II to IV per New York Heart
             Association (NYHA) classification; active coronary artery disease (CAD); clinically
             significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade
             3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction
             occurring within 6 months prior to study entry (myocardial infarction occurring > 6
             months prior to study entry is permitted)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study

          -  Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral
             therapy are ineligible