Study Evaluating Bosutinib-Letrozole Combination Versus Letrozole Alone In Post Menopausal Women With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Bosutinib; Letrozole; Letrozole
Intervention description: 400mg (4x100)mg tablets once daily during the active phase of treatment until Disease Progression, unacceptable toxicity or withdraw of consents occurs; 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; 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
Intervention MeSH terms: Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)
Enrollment: 16.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 2 study of bosutinib administered in combination with letrozole versus
      letrozole alone in post-menopausal women with breast cancer. This is a 2-part study. Subjects
      in part 1 will receive bosutinib and letrozole daily, and will be closely monitored for 28
      days. The second part will proceed with subjects receiving a dose that is determined to be
      safe based on the safety evaluation of the first part. Eligible subjects will be randomly
      assigned to receive either bosutinib daily combined with daily letrozole, or daily letrozole
      alone for a specified period of time. Subjects will be followed up for survival after study
      drug discontinuation.
    

Eligibility criteria:

        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.