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
- 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
- Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue
- No 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 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
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Hemoglobin ≥ 9.0 g/dL
- Leukocytes ≥ 3,000/mcL
- 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
- Female subjects of childbearing potential must have a negative serum pregnancy test
within 21 days of cycle 1 day 1
- 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
- Ability to understand and the willingness to sign a written informed consent document
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to ARQ 197
- No 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) 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)
- No 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
- Not pregnant or nursing
- Human immunodeficiency virus (HIV)-positive participants on combination
antiretroviral therapy are ineligible
- See Disease Characteristics
- Any treatment-related toxicity should have resolved to ≤ grade 1 per Common
Terminology Criteria for Adverse Events (CTCAE)
- 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
- Participants on bisphosphonates may continue receiving bisphosphonate therapy during
study treatment
- Bisphosphonate therapy may also be initiated on study treatment if needed
- No participants who have received chemotherapy, biologic, investigational, or
radiotherapy within 14 days prior to entering the study
- No participants who are receiving any other investigational agents