ARQ197 in Metastatic Triple-Negative Breast Cancer

• Objective Response Based on RECIST [ Time Frame: Patients will be followed until disease progression ] [ Designated as safety issue: No ]
  To evaluate objective response based on RECIST 1.1 criteria
• Evaluate c-Met [ Time Frame: Will be done on archival tumor tissue ] [ Designated as safety issue: No ]
  To evaluate c-Met and phosph c-Met expression in archival tumor tissue
• Evaluate Incidence of c-Met Positive Circulating Tumor Cells [ Time Frame: Will be done on baseline blood sample ] [ Designated as safety issue: No ]
  To evaluate the incidence of c-Met positive circulating tumor cells at baseline
• Effect of ARQ 197 on Serum Markers [ Time Frame: Will be done on blood samples obtained at the start of each cycle of therapy ] [ Designated as safety issue: No ]
  Evaluate the effect of ARQ-197 on serum markers relevant to c-Met pathway
• Proportion of Patients with Basal-like Breast Cancer [ Time Frame: Will be done on archival tumor tissue ] [ Designated as safety issue: No ]
  Evaluate the proportion of patients with basal-like breast cancer

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not yet approved ARQ 197 for use in patients, including patients with your type of cancer.

ARQ 197 is a drug that has been shown to slow down tumor cell growth and motility signals, which affects movement. This drug has been used in other research studies and information from those studies suggests that ARQ 197 may help to treat your cancer.

The purpose of this research study is to find out what effects ARQ 197 has on you and your cancer.

If you take part in this research study, you will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 3 weeks during which time you will be taking the study drug twice daily for 21 days. During all cycles you will have a physical exam and will be asked questions about your general healthy and specific questions about any problems that you might be having and any medications you may be taking. Physical exams will occur in clinic on screening, day 15, day 29, day 43 and every two weeks.

After the final dose of the study drug your research doctor will ask you to visit the office for a follow-up exam approximately 30 to 37 days after discontinuing therapy. At this visit you will have a physical exam, vital signs, blood tests and be asked about any symptoms you may be experiencing since stopping ARQ 197. You will be followed approximately every 6 months after removal from the study.

Inclusion Criteria:

• Histologically or cytologically confirmed, triple-negative (ER-, PR-, HER2-) invasive breast cancer with recurrent or metastatic disease
• Measurable disease
• Must have received 1-3 prior chemotherapeutic regimens for metastatic breast cancer m
• Must have been off treatment with chemotherapy, biologic therapy, investigational therapy and radiation therapy for at least 14 days before enrollment in the study
• ECOG performance status of less than or equal to 2
• Either the primary tumor or the metastasis must be triple-negative
• Confirmed availability of FFPE tumor tissue

Exclusion Criteria:

• Pregnant or breastfeeding
• Have received treatment within the past 14 days
• Known brain metastases that are untreated, symptomatic or require therapy to control symptoms
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ197
• History of congestive heart failure, active coronary artery disease, uncontrolled hypertension, myocardial infarction within 6 months
• Uncontrolled intercurrent illness
• HIV positive on combination antiretroviral therapy