Exemestane With Sunitinib (SUTENT®) in Metastatic Breast Cancer

The study design is a phase II design. Eligible patients will undergo staging work up and start treatment. Every 28-day period (4 weeks) will count as a cycle. Medical evaluations will be performed every 4 weeks and staging work up will be repeated every 12 weeks.

The primary objective of the study is to assess progression free survival (PFS) of treatment with exemestane and sunitinib in post¬menopausal subjects with hormone receptor positive (ER-positive and/or PR-positive) unresectable locally advanced or metastatic breast cancer subjects who have progressed on prior hormonal treatment.

In addition we want to:

1. Obtain assessments of overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS).
2. Determine the safety and tolerability of the combination regimen.
3. Study molecular changes in tissue biopsies, circulating tumor cells (CTCs), and circulating endothelial cells (CECs), and explore associations with treatment response and resistance.

1. Blood samples will be drawn for enumeration and profiling of circulating tumor cells and circulating endothelial cells at study entry (prior to starting study medications), four weeks after starting study medications, twelve weeks after starting study medications and at disease progression. These samples will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study.

2. If the patient participating on the study has an easily accessible breast mass or metastatic lesion (e.g. lymphadenopathy, skin metastasis, chest wall metastasis), a core needle or punch biopsy will be obtained at study entry (prior to starting study medications), four weeks after starting study medications, and at disease progression. These biopsies will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study.

• Drug: Exemestane
  Exemestane 25 mg by mouth every day.
  Other Name: Aromasin
• Drug: Sutent
  Sunitinib 37.5 mg by mouth every day.
  Other Name: (Sunitinib)

Inclusion Criteria:

1. Must have metastatic breast cancer or locally advanced not amenable to curative therapy.
2. Measurable or evaluable disease are eligible.
3. Tumors must be Estrogen Receptor (ER)-positive and/or Progesterone Receptor (PR)-positive.
4. Human Epidermal Growth Factor Recepter 2 (HER2)-positive tumors are allowed but must have failed Herceptin therapy.
5. Postmenopausal
6. No more than 3 lines of chemotherapy
7. No more than 3 lines of hormonal therapy
8. Bisphosphonates may be given according to their product license
9. Left ventricular ejection fraction within institutional normal limits
10. Liver function and kidney function tests within the upper limit of normal. In patients with liver metastasis, liver function tests should be < 5 times the upper limit of normal.
11. Adequate blood counts
12. Normal thyroid function tests.
13. Patients with Central Nervous System (CNS) metastatic disease are allowed if the disease is stable for more than 3 months by CT or MRI.
14. Adequate general health (Eastern Cooperative Oncology Group (ECOG) performance status 0-2).
15. Able to give informed consent and follow the procedures of the study.

Exclusion Criteria:

1. Patients previously treated with exemestane in any setting.
2. Patients previously treated with sunitinib.
3. Patients with cardiac dysfunction or active cardiac disease
4. Patients with uncontrolled CNS metastasis.
5. Poorly controlled hypertension
6. Blood counts or liver and kidney tests that fall outside the ranges outlined in inclusion criteria 9-10 above.
7. ECOG performance status 3 or 4.
8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin.
9. History of a cerebrovascular accident, non-catheter related deep vein thrombosis, or pulmonary embolism in the last 5 years.
10. Major surgical procedure or significant traumatic injury within 28 days prior to study entry.
11. Premenopausal status.
12. History of receiving any investigational treatment within 28 days of study medication initiation.
13. Current known infection.
14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
15. Medical or psychiatric condition that in the opinion of the principal investigator impair their ability to participate in the study.