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continued until disease progression unless there is evidence of unacceptable toxicity or if the patient requests to be withdrawn from the study.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)
Tbilisi Cancer Center
🇬🇪Tbilisi, Georgia
Ipo Porto
🇵🇹Porto, Portugal
Bacs-Kiskun County Hospital
🇭🇺Kalocsa, Hungary
Institut Sainte Catherine
🇫🇷Avignon, France
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, Germany
Schwarzwald Baar Klinikum, Villingen-Schwenningen
🇩🇪Villingen-Schwenningen, Germany
Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
Antoine Lacassagne Centre De Lutte Contre Le Cancer De Nice
🇫🇷Nice, France
ICO Paul Papin
🇫🇷Angers, France
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
Klinik für Gynäkologie & Geburtshilfe/Brustzentrum
🇩🇪Frankfurt, Germany
Hospital Ico Josep Trueta
🇪🇸Girona, Spain
Praxis für Innere Medizin
🇩🇪Singen, Germany
Onkologische Praxis
🇩🇪Oldenburg, Germany
Cafeteria Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Son Llàtzer
🇪🇸Palma, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Centre Paul Strauss
🇫🇷Strasbourg, France
Praxis für interdisziplinäre Onkologie & Hämatologie
🇩🇪Freiburg, Germany
National Cancer Center South Korea
🇰🇷Goyang, Korea, Republic of
Kliniken Essen-Mitte Senologie
🇩🇪Essen, Germany
Hospital Center Private Saint-Grégoire
🇫🇷Saint-Grégoire, France
St. Vincentius Kliniken
🇩🇪Karlsruhe, Germany
Dokusan GmbH
🇩🇪Herne, Germany
Wansbeck General Hospital
🇬🇧Ashington, United Kingdom
Korea University Medical Center Guro Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Clinico Universitario San Carlos
🇪🇸Madrid, Spain
Frauenärztliche Gemeinschaftspraxis - Onkologie
🇩🇪Braunschweig, Germany
MediProjekt GbR Hannover
🇩🇪Hannöver, Germany
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castelló, Spain
MVZ Klinik Dr. Hancken GmbH
🇩🇪Stade, Germany
Mutterhaus der Borromäerinnen
🇩🇪Trier, Germany
Hospital da Luz
🇵🇹Lisboa, Portugal
Center of Oncology Euroclinic
🇷🇴Bucharest, Romania
Oncology Center Oncolab Craiova
🇷🇴Craiova, Romania
Instituto Oncologico Dr. Rosell
🇪🇸Barcelona, Spain
University Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital Son Espases
🇪🇸Palma De Mallorca, Spain
Princess of Wales Hospital
🇬🇧Bridgend, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, United Kingdom
Royal Glamorgan Hospital
🇬🇧Llantrisant, United Kingdom
Charring Cross Hospital
🇬🇧London, United Kingdom
Mount Vernon Hospital
🇬🇧London, United Kingdom
Saint Bartholomew's Hospital
🇬🇧London, United Kingdom
The Royal Free Hospital
🇬🇧London, United Kingdom
The Kent Oncology Centre
🇬🇧Maidstone, United Kingdom
North Tyneside General Hospital
🇬🇧North Shields, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Southend University Hospital
🇬🇧Southend-on-Sea, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
King's Mill Hospital
🇬🇧Sutton in Ashfield, United Kingdom
Queen Elizabeth Hospital, Woolwich
🇬🇧London, United Kingdom
Cumberland Infirmary
🇬🇧Carlisle, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, United Kingdom
University Hospital of North Durham
🇬🇧Durham, United Kingdom
Calderdale Royal Hospital
🇬🇧Halifax, United Kingdom
Kidderminster Hospital
🇬🇧Kidderminster, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Solihull Hospital
🇬🇧Solihull, United Kingdom
Great Western Hospital
🇬🇧Swindon, United Kingdom
Wrexham Maelor
🇬🇧Wrexham, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, United Kingdom
S. Khechinashvili University Clinic
🇬🇪Tbilisi, Georgia
Zala County Szent Rafael Hospital
🇭🇺Zalaegerszeg, Hungary
Clinic Health House
🇬🇪Tbilisi, Georgia
University of Pecs, Institute of Oncology
🇭🇺Pécs, Hungary
Oncology Center Sf Nectarie
🇷🇴Caracal, Romania
Queen Mary University of London
🇬🇧London, United Kingdom
Oncology Institute "Prof. Dr. Ion Chiricuta"
🇷🇴Cluj-Napoca, Romania
Cluj County Clinical Emergency Hospital, Clinical Department of Medical Oncology
🇷🇴Cluj-Napoca, Romania
Uzsoki Street Hospital
🇭🇺Budapest, Hungary
Schwerpunktpraxis Hämatologie / Onkologie MVZ Lahr
🇩🇪Lahr, Germany
Klinikum Neumarkt
🇩🇪Neumarkt, Germany
Hospital Universitario de Canarias
🇪🇸San Cristobal de la Laguna, Spain
Hospital Universitari Sant Joan de Reus
🇪🇸Tarragona, Spain