Clinical trial NCT01575522 (phase 2, status: completed)
Conditions: estrogen receptor negative, her2/neu negative, progesterone receptor negative, recurrent breast carcinoma, stage iv breast cancer, triple-negative breast carcinoma
ICD codes: Z17.1, A41.50, A41.59, E70.320, Z17.1, Z67.11, Z67.21, Z67.31, Z17.0, Z17.1, T47.0X6S, T50.7X6S, T47.0X3S, T47.0X4S, T47.0X5S, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31
Drugs: tivantinib
SMILES: O=C1NC(=O)[C@H]([C@@H]1C1=CNC2=CC=CC=C12)C1=CN2CCCC3=C2C1=CC=C3
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