NCT02216786

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

A Randomized Phase II Study of Fulvestrant in Combination With the Dual mTOR Inhibitor AZD2014 or Everolimus or Fulvestrant Alone in Estrogen Receptor-positive Advanced or Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 333 (actual)
• Sponsor: Queen Mary University of London · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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)

Detailed description

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) Sensitivity to prior endocrine therapy is defined as (i) at least 24 months of endocrine therapy before recurrence in the adjuvant setting or (ii) a complete or partial response to prior metastatic endocrine treatment, or (iii) stabilization for at least 24 weeks of endocrine therapy for advanced disease. Treatment will be continued until disease progression unless there is evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study. If one of the treatments (fulvestrant or mTOR inhibitor) is discontinued prior to disease progression, patients should be continued on single agent treatment until progression, evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study. At the time of documented disease progression (using RECIST 1.1), patients randomised to receive fulvestrant + everolimus who still meet eligibility criteria may be permitted to receive open-label crossover treatment with fulvestrant + AZD2014. Crossover therapy must begin no later than 28 days after the clinic visit at which progression was determined. Patients will receive crossover therapy until progression, intolerable toxicity, elective withdrawal from the study, or until the completion or termination of the study, whichever occurs first. Tumour evaluations will be performed before the initiation of treatment, every 8 weeks during the first 40 weeks and every 12 weeks thereafter until disease progression. The study will also assess the relationship between the anticipated anti-tumour activity of the treatment regimen and biological characteristics of patients' tumour at baseline

Conditions

• Estrogen Receptor Positive Breast Cancer

Interventions

Type	Name	Description
DRUG	AZD2014	Oral tablet
DRUG	Everolimus	Oral tablet
DRUG	Fulvestrant	Im injection

Timeline

• Start date: 2014-01-16
• Primary completion: 2021-12-31
• Completion: 2021-12-31
• First posted: 2014-08-15
• Last updated: 2024-12-02

Locations

79 sites across 9 countries: France, Georgia, Germany, Hungary, Portugal, Romania, South Korea, Spain, United Kingdom