This randomized Phase III trial studies how well the combination of fulvestrant and everolimus together or the combination of anastrozole, fulvestrant and everolimus together, improve progression-free survival (PFS) versus fulvestrant alone.
OBJECTIVES: Primary * To test the benefit of interfering with the function of the estrogen receptor (ER) and providing downstream target inhibition (PI3K/AKT/mTOR) with a combination of optimal dose fulvestrant and everolimus (Arm 2) to improve progression-free survival compared to the optimal dose fulvestrant alone (Arm 1). * To test the benefit of adding the non-steroidal aromatase inhibitor anastrozole to optimal dose fulvestrant and everolimus (Arm 3) in order to improve progression free survival over optimal dose fulvestrant (Arm 1). Secondary * To compare progression-free survival among those receiving fulvestrant + everolimus + anastrozole (Arm 3) versus fulvestrant + everolimus (Arm 2). * To compare overall survival among the treatment arms in post-menopausal patients with hormone-receptor positive (HR+) Stage IV breast cancer. * To assess and compare toxicities, feasibility and compliance among the study regimens. * To compare response rates and clinical benefit rates among the study regimens. * To test molecular determinants of response to endocrine therapy and everolimus in circulating tumor cells: 1. CTC-Endocrine Therapy Index (CTC ETI) on the CellSearch® platform. 2. CTC-Next Generation Sequencing Analysis (CTC-NGS) of single cells captured on the HD-CTC® platform. OUTLINE: This is a multicenter study. Patients will be stratified according to the following factors: * Measurable versus evaluable non-measurable disease * Prior adjuvant hormonal therapy completed more than 5 years ago vs. prior adjuvant hormonal therapy completed 1-5 years ago vs. de novo presentation of metastatic disease or no prior adjuvant hormonal therapy. ARMS: * Arm 1: fulvestrant + placebo (everolimus) + placebo (anastrozole) * Arm 2: fulvestrant + everolimus + placebo (anastrozole) * Arm 3: fulvestrant + everolimus + anastrozole Blood and tissue samples are collected for correlative science studies. After completion of study treatment, patients are followed up every 6 months for 2 years and then yearly thereafter for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
37
Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus )
From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive are censored at date of last contact.
Time frame: up to 5 years
Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole)
From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time frame: up to 5 years
Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole)
From date of registration to date of first documentation of progression or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time frame: up to 5 years
Overall Survival
From date of registration to date of death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
Time frame: up to 5 years
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Duration of treatment and follow up until death or 5 years post registration
Response Rate
Proportion of participants who have confirmed or unconfirmed partial or complete response to therapy
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Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Virginia G. Piper Cancer Center
Scottsdale, Arizona, United States
University of Arizona Cancer Center - Orange Grove
Tucson, Arizona, United States
University of Arizona Cancer Center - North Campus
Tucson, Arizona, United States
Southern Arizona VA Health Care System
Tucson, Arizona, United States
University of Arizona Medical Center - Univ Campus
Tucson, Arizona, United States
...and 213 more locations
Time frame: assessed every 12 weeks, up to 5 years
Clinical Benefit Rate
Proportion of participants who have confirmed and unconfirmed partial response, complete response or stable disease.
Time frame: assessed every 12 weeks, up to 5 years
Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI
CTC-Endocrine Therapy Index (CTC-ETI) on the CellSearch® platform. Based on enumeration of CTC/7.5 mL of whole blood, with \>= 5 being elevated. (Due to limited samples collected, full analysis was not able to be performed as planned, so outcome measure reported here is number with elevated Day 1 CTC.)
Time frame: Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.)