Enhancing Efficacy of Chemotherapy in Triple Negative/Basal-Like Breast Cancer by Targeting Macrophages: A Multicenter Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer

Inclusion Criteria:

- Pathologically confirmed diagnosis of breast cancer with documented progressive
disease.

- Patients with stable brain metastases are eligible for this trial.

- At least one prior chemotherapy regimen for metastatic breast cancer. Prior
treatment must be discontinued at least 2 weeks before treatment start.

- Concomitant therapy with bisphosphonates is allowed.

- Stable dose coumadin anticoagulation is allowed, providing that anticoagulation can
be safely held to an INR within normal range for the purpose of tumor biopsy. LMWH is
the preferred method of anticoagulation.

- PT/INR and PTT within institutional normal limits within two weeks before initial
biopsy.

- Measurable disease, as defined by RECIST guidelines or evaluable disease. Bone
metastases must be evaluable.

- Disease amenable to core biopsy. Patients with pulmonary metastases as their only
site of disease may enroll on this trial and will not undergo biopsy.

- For Phase I: patients with HER2 overexpressing disease must have been previously
treated with trastuzumab. Patients with HER2 overexpressing disease are not
eligible for the Phase II trial.

- Age eighteen years or older.

- ECOG performance status
- Life expectancy of >/= 12 weeks.

- Patients with < grade 1 peripheral neuropathy are eligible for this trial.

- Adequate bone marrow reserve: ANC >/= 1000, platelets >/= 100,000.

- Adequate renal function: serum creatinine calculated creatinine clearance ≥ 50 ml/min.

- Sodium, potassium, and chloride levels within institutional normal limits.

- Adequate hepatic function: AST and ALT upper limit of normal. In patients with liver dysfunction due to hepatic metastases,
AST and ALT are permitted to be
- At baseline: EF ≥ 50%, no evidence of QT prolongation, no history of congenital long
QT syndrome, and no use of drugs known to increase the risk of Torsades de Point -
patients may be eligible for study if the drug can be changed to another agent with
less risk (such as changing from citalopram to an alternate antidepressant).

- Able to take oral medications and maintain hydration.

- Ability to give written informed consent and willingness to comply with the
requirements of the protocol

- Women of child-bearing potential must agree to use an effective method of birth
control during treatment and for six months after receiving their last dose of study
drug

Specific inclusion criteria for Phase II

• Patients enrolling on the phase II portion of this trial must have ER, PR and HER2
negative disease defined as less than 10% staining for ER and PR, and HER2 not amplified
by FISH, 0-1% by IHC, or 2+ by IHC and no evidence of amplification by FISH.

Exclusion Criteria:

- Treatment with another chemotherapy or hormonal therapy within the past 2 weeks.

- Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2
weeks.

- Concurrent treatment with radiotherapy.

- Ongoing treatment with any other investigational therapy.

- Prior treatment with eribulin

- Severe, concurrent illness including congestive heart failure, significant cardiac
disease and uncontrolled hypertension, that would likely prevent the patient from
being able to comply with the study protocol.

- Inadequate bone marrow, renal, or hepatic function as defined above, or an active
coagulopathy that precludes tissue biopsy.

- Pregnant or lactating women and women of child-bearing potential who are not using an
effective method of birth control. Women of childbearing potential must undergo a
serum pregnancy test within seven days of starting the study drug.