Alisertib and Fulvestrant in Treating Patients With Hormone Receptor Positive Breast Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery
This phase I trial studies the side effects and best dose of alisertib when given together with fulvestrant in treating patients with hormone positive breast cancer that has spread to other parts of the body or is locally advanced and cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are type of hormones made by the body and they can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen or progesterone the body makes. Giving alisertib together with fulvestrant may be a better treatment for breast cancer.
Estrogen Receptor Positive
Progesterone Receptor Positive
Recurrent Breast Carcinoma
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]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.
- Progression-free survival (PFS) [ Time Frame: Time from study entry to the documentation of disease progression, assessed up to 1 month after completion of treatment ] [ Designated as safety issue: No ]
- Overall survival time [ Time Frame: Time from study entry to death due to any cause, assessed up to 1 month ] [ Designated as safety issue: No ]
- Tumor response (complete or partial response) using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 1 month post-treatment ] [ Designated as safety issue: No ]The number of confirmed tumor response will be tabulated for each dose level.
- Aurora A kinase (AURKA) expression levels [ Time Frame: Baseline ] [ Designated as safety issue: No ]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 PFS 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 ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2014|
|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|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Tufia C. Haddad|
|Principal Investigator:||Tufia Haddad||Mayo Clinic|