S1222 Trial (Everolimus, Anastrozole and Fulvestrant) in Post-Menopausal Stage IV Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Drug: Placebo - Everolimus
- Registration Number
- NCT02137837
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: fulvestrant + everolimus placebo + anastrozole placebo Placebo - Everolimus Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. Arm 1: fulvestrant + everolimus placebo + anastrozole placebo Placebo - Anastrozole Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. Arm 2: fulvestrant + everolimus + anastrozole placebo Placebo - Anastrozole Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. Arm 1: fulvestrant + everolimus placebo + anastrozole placebo Fulvestrant Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral placebo daily for both everolimus and anastrozole. This treatment regimen will continue until disease progression or toxicity. Arm 2: fulvestrant + everolimus + anastrozole placebo Fulvestrant Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. Arm 2: fulvestrant + everolimus + anastrozole placebo Everolimus Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive an oral everolimus and an oral placebo for anastrozole daily. This treatment regimen will continue until disease progression or toxicity. Arm 3: fulvestrant + everolimus + anastrozole Fulvestrant Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. Arm 3: fulvestrant + everolimus + anastrozole Anastrozole Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity. Arm 3: fulvestrant + everolimus + anastrozole Everolimus Patients receive an injection of fulvestrant in each buttock on Days 1 \&15 for Cycle 1 and then Day 1 only for subsequent cycles. Patients also receive everolimus and anastrozole by mouth daily. This treatment regimen will continue until disease progression or toxicity.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (Fulvestrant vs Fulvestrant + Everolimus ) up to 5 years 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.
Progression-free Survival (Fulvestrant Versus Fulvestrant + Everolimus + Anastrozole) up to 5 years 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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (Fulvestrant + Everolimus vs Fulvestrant + Everolimus + Anastrozole) up to 5 years 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.
Overall Survival up to 5 years 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.
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Duration of treatment and follow up until death or 5 years post registration 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.
Response Rate assessed every 12 weeks, up to 5 years Proportion of participants who have confirmed or unconfirmed partial or complete response to therapy
Clinical Benefit Rate assessed every 12 weeks, up to 5 years Proportion of participants who have confirmed and unconfirmed partial response, complete response or stable disease.
Molecular Determinants of Response in Circulating Tumor Cells: CTC-ETI Day 1, Day 29, time of progression (Day 29 to be collected only if Day 1 CTC was elevated.) 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.)
Trial Locations
- Locations (223)
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
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