A Randomized Study of AZD2014 in Combination With Fulvestrant in Metastatic or Advanced Breast Cancer
- Conditions
- Estrogen Receptor Positive Breast Cancer
- Interventions
- Registration Number
- NCT02216786
- Lead Sponsor
- Queen Mary University of London
- Brief 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continued until disease progression unless there is evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study.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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 333
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus and Fulvestrant Everolimus Comparator arm Fulvestrant +AZD2014 (intermittent) AZD2014 Experimental arm Fulvestrant and AZD2014 (continuous) AZD2014 Experimental arm Fulvestrant and AZD2014 (continuous) Fulvestrant Experimental arm Everolimus and Fulvestrant Fulvestrant Comparator arm Fulvestrant Fulvestrant Control 1 Fulvestrant +AZD2014 (intermittent) Fulvestrant Experimental arm
- Primary Outcome Measures
Name Time Method Progression-free survival Date of randomisation to date of first documented progression, assessed up to 100 weeks Defined as the time from the date of randomisation to the date of first documented tumour progression based on investigator assessment (using RECIST 1.1) or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Objective response Time from date of randomisation to documented objective response, assessed up to 60 months Time from date of randomisation to documented objective response, defined as a complete or partial response, based on investigator and IRF assessment (using RECIST 1.1)
Progression-free survival time from the date of randomisation to the date of first documented tumour progression, assessed up to 100 weeks Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression as assessed by an independent review facility \[IRF\] (using RECIST 1.1) or death from any cause, whichever occurs first.
Average change (%) in tumour size 16 weeks after baseline Average change (%) in tumour size at 16 weeks compared to baseline, based on investigator and IRF assessment using RECIST 1.1; tumour size is defined as the sum of the longest diameters of the target (i.e. measurable tumour) lesions
Clinical Benefit (CB) Date of randomisation to 24 weeks. Clinical Benefit (CB), defined as number of patients with complete or partial response or stable disease maintained ≥24 weeks, based on investigator and IRF assessment using RECIST 1.1.
Trial Locations
- Locations (79)
ICO Paul Papin
🇫🇷Angers, France
Institut Sainte Catherine
🇫🇷Avignon, France
Antoine Lacassagne Centre De Lutte Contre Le Cancer De Nice
🇫🇷Nice, France
Hospital Center Private Saint-Grégoire
🇫🇷Saint-Grégoire, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Clinic Health House
🇬🇪Tbilisi, Georgia
Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
S. Khechinashvili University Clinic
🇬🇪Tbilisi, Georgia
Tbilisi Cancer Center
🇬🇪Tbilisi, Georgia
Frauenärztliche Gemeinschaftspraxis - Onkologie
🇩🇪Braunschweig, Germany
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