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
Overview
- Phase
- Phase 1
- Intervention
- Alisertib
- Conditions
- Estrogen Receptor Positive
- Sponsor
- Mayo Clinic
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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 has spread from where it started to nearby tissue or lymph nodes 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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose of alisertib in combination with fulvestrant. SECONDARY OBJECTIVES: 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. TERTIARY OBJECTIVES: 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic proof of metastatic or locally advanced, unresectable breast cancer which is estrogen receptor positive and/or progesterone positive per institutional standards
- •Non-measurable or measurable disease
- •Post-menopausal women, as verified by:
- •Post bilateral surgical oophorectomy, or
- •No spontaneous menses \>= 1 year, or
- •No menses for \< 1 year with follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range, according to institutional standards
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3
- •Platelet (PLT) \>= 100,000/mm\^3
- •Total bilirubin =\< 1.5 upper limit of normal (ULN)
- •Alanine transaminase (ALT) =\< 3 x ULN (=\< 5 x ULN for patients with liver involvement)
Exclusion Criteria
- •Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Any of the following prior therapies:
- •Chemotherapy =\< 21 days prior to registration
- •Mitomycin C/nitrosoureas =\< 42 days prior to registration
- •Immunotherapy =\< 28 days prior to registration
- •Biologic therapy =\< 28 days prior to registration
- •Radiation therapy =\< 21 days prior to registration
- •Radiation to \> 25% of bone marrow prior to registration
- •Hormonal therapy =\< 14 days prior to registration
Arms & Interventions
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.
Intervention: Alisertib
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.
Intervention: Fulvestrant
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.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Tumor response (complete or partial response) using Response Evaluation Criteria in Solid Tumors version 1.1(Up to 1 month post-treatment)