Alisertib and Fulvestrant in Treating Patients With Hormone Receptor Positive Breast Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery
|Estrogen Receptor Positive Progesterone Receptor Positive Recurrent Breast Carcinoma Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer||Drug: Alisertib Drug: Fulvestrant Other: Laboratory Biomarker Analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Trial to Evaluate the Safety of the Addition of Alisertib to Fulvestrant in Women With Advanced Hormone Receptor Positive (HR+) Breast Cancer|
- Maximum tolerated dose (MTD) of alisertib in combination with fulvestrant graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ]The MTD is defined as the highest dose level among those under consideration where at most 1 of 6 patients develops a dose limiting toxicity and 2 or more of the 3-6 patients treated at the next higher dose level develop a dose limiting toxicity. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.
- Tumor response (complete or partial response) using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 1 month post-treatment ]The number of confirmed tumor response will be tabulated for each dose level.
- Aurora A kinase (AURKA) expression levels [ Time Frame: Baseline ]The percentage of patients who develop a DLT among those who have high AURKA expressing breast cancer and those who do not will be tabulated. The progression free survival times of those who have high aurora A kinase expressing breast cancer and those who do not will be determined and visually compared and contrasted.
- Expression levels of ER-alpha, SMAD family member 5 (P~SMAD5), (sex determining region Y)-box 2 (SOX-2), E-cadherin, vimentin, cluster of differentiation (CD)44, CD24, and protein C receptor, endothelial (PROCR) [ Time Frame: Up to 1 month post-treatment ]Cross tables of AURKA expression levels with expression levels of ER-alpha, P~SMAD5, SOX2, E-cadherin, Vimentin, CD44, CD24, and PROCR will be constructed to examine patterns of association between the biomarkers.
|Actual Study Start Date:||September 2014|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||September 2019 (Final data collection date for primary outcome measure)|
Experimental: Treatment (alisertib, fulvestrant)
Patients receive fulvestrant IM on day 1 (days 1 and 15 of course 1 only) and 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.
Other Names:Drug: Fulvestrant
Other Names:Other: Laboratory Biomarker Analysis
I. To determine the maximally tolerated dose of alisertib in combination with fulvestrant.
I. To describe the safety and tolerability of alisertib in combination with fulvestrant.
II. To examine tumor response in postmenopausal women treated with alisertib in combination with fulvestrant.
I. To assess aurora A kinase expression in archived breast cancer tissue biospecimens of participants, and to describe levels in those who do or do not experience dose-limiting toxicities (DLTs) or objective response.
OUTLINE: This is a dose-escalation study of alisertib.
Patients receive fulvestrant intramuscularly (IM) on day 1 (days 1 and 15 of course 1 only) and 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.
After completion of study treatment, patients are followed up at 1 month.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02219789
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Tufia Haddad||Mayo Clinic|