Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer

• Drug: Bosutinib
  400mg (4x100)mg tablets once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs
• Drug: Letrozole
  2.5 mg - one tablet per day- once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs

• Experimental: 1
  Combination of Bosutinib and Letrozole
  Interventions:

  • Drug: Bosutinib
  • Drug: Letrozole
• Active Comparator: 2
  Letrozole
  Intervention: Drug: Letrozole

Inclusion Criteria:

• Surgically sterile or post-menopausal women.
• Confirmed pathologic diagnosis of breast cancer.
• Locally advanced or metastatic, or loco-regional recurrent breast cancer not amenable to curative treatment with surgery or radiotherapy.
• Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory.
• At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

• Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior Src inhibitor.
• Prior endocrine treatment for locally advanced or metastatic breast cancer (up to one prior adjuvant Aromatase Inhibitor (AI) agent/regimen is permitted).
• More than 1 prior chemotherapy regimen in locally advanced or metastatic breast cancer.
• Adjuvant endocrine therapy <=12 months prior to day 1 of treatment.
• Disease refractory (ie, Progressive disease (PD) within 6 months from initiation of therapy) to previous adjuvant antiestrogen therapy.
• Bone or skin as the only site of disease.
• Extensive visceral disease or active Central Nervous System (CNS) disease.
• Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
• Major surgery or radiotherapy within 14 days of treatment day.
• Inadequate hepatic/renal/bone marrow function.
• History of clinically significant or uncontrolled cardiac disease.
• Serious concurrent illness.