A Randomized Study of AZD2014 in Combination With Fulvestrant in Metastatic or Advanced Breast Cancer

Summary

This is an open-label, multicentre, 4-arm randomised phase II trial of fulvestrant + AZD2014 versus fulvestrant + everolimus versus fulvestrant alone in patients with ER-positive, HER2-negative advanced or metastatic breast cancer, whose disease relapsed during treatment with (or within 12 months after discontinuation of) an AI in the adjuvant setting or progressed during treatment with an AI in the metastatic setting. Patients will be randomised (2:3:3:2) to one of the four treatment arms: * Fulvestrant * Fulvestrant + AZD2014 (continuous daily schedule) * Fulvestrant + AZD2014 (intermittent schedule - 2 days on, 5 days off) * Fulvestrant + everolimus Randomization will be stratified by the following criteria: * Measurable disease (vs. non-measurable). * Sensitivity to prior endocrine therapy (sensitive versus resistant)

Timeline

Start

2014-01-16

Primary completion

2021-12-31

Completion

2021-12-31

Outcome

Missed primary endpoint

paper There was no significant difference in PFS between those receiving fulvestrant plus daily or intermittent vistusertib and fulvestrant alone PMID 31465093 ↗

paper The trial failed to demonstrate a benefit of adding the dual mTORC1 and mTORC2 inhibitor vistusertib to fulvestrant. PMID 31465093 ↗

Publications

• Results Schmid P, Zaiss M, Harper-Wynne C, Ferreira M, Dubey S, Chan S, Makris A, Nemsadze G, Brunt AM, Kuemmel S, Ruiz I, Perello A, Kendall A, Brown J, Kristeleit H, Conibear J, Saura C, Grenier J, Mahr K, Schenker M, Sohn J, Lee KS, Shepherd CJ, Oelmann E, Sarker SJ, Prendergast A, Marosics P, Moosa A, Lawrence C, Coetzee C, Mousa K, Cortes J. Fulvestrant Plus Vistusertib vs Fulvestrant Plus Everolimus vs Fulvestrant Alone for Women With Hormone Receptor-Positive Metastatic Breast Cancer: The MANTA Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1556-1564. doi: 10.1001/jamaoncol.2019.2526.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Everolimus	Small molecule	—	Oral
Subject	Fulvestrant	Small molecule	—	Intramuscular
Subject	Vistusertib	Small molecule	—	Oral

Indications