Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer

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PRIMARY OBJECTIVES: I. To assess the impact on objective tumor response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria) with the addition of fulvestrant to alisertib in women with endocrine resistant, advanced estrogen receptor positive breast cancer. SECONDARY OBJECTIVES...

PRIMARY OBJECTIVES: I. To assess the impact on objective tumor response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria) with the addition of fulvestrant to alisertib in women with endocrine resistant, advanced estrogen receptor positive breast cancer. SECONDARY OBJECTIVES: I. To evaluate the safety profile of each treatment regimen. II. To assess the impact on median progression-free survival with the addition of fulvestrant to alisertib. III. To obtain estimated tumor response rate and the median progression-free survival time during alisertib and fulvestrant treatment in the cohort of patients who progress during alisertib monotherapy, and crossover to receive the combination of alisertib and fulvestrant. TERTIARY OBJECTIVES: I. To assess the changes in aurora A kinase, SMAD5 and SOX2 expression and phosphorylation in tumor tissue after first cycle of assigned treatment. II. To assess the changes in estrogen receptor (ER) expression and function in tumor tissue after the first cycle of assigned treatment. III. To generate patient derived xenografts (PDX) from tumors collected at baseline and progression of disease (PD) in order to identify mechanisms associated with both de novo and acquired alisertib resistance. IV. After the first cycle of treatment, to assess changes in aurora A kinase, phosphorylated (p)~SOX2 and ER expression on circulating tumor cells (CTCs), and to assess concordance between change in expression with tumor tissue and CTCs. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive alisertib orally (PO) twice daily (BID) on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II. ARM II: Patients receive fulvestrant intramuscularly (IM) over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 5 years.

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