S1222 Trial (Everolimus, Anastrozole and Fulvestrant) in Post-Menopausal Stage IV Breast Cancer

Breast Cancer Clinical Trial

Official title: Fulvestrant Alone Versus Fulvestrant and Everolimus Versus Fulvestrant, Everolimus and Anastrozole: A Phase III Randomized Placebo-Controlled Trial in Postmenopausal Patients

Status Terminated

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT02137837
• Study type: Interventional
• Source: Southwest Oncology Group
• Status: Terminated
• Phase: Phase 3
• Start date: May 2014
• Completion date: December 31, 2019