Fulvestrant and EVerolimus Plus EXemestane in Metastatic Breast Cancer
FEVEX
Fulvestrant Followed by Everolimus Plus Exemestane vs Examestane and Everolimus Followed by Fulvestrant in Postmenopausal Women With HR+ and HER2- Locally Advanced (LABC) or Metastatic Breast Cancer (MBC) Previously Treated With NSAI
2 other identifiers
interventional
745
1 country
41
Brief Summary
This is a multi-center, randomized, open-label, parallel group study designed to evaluate efficacy and safety of fulvestrant followed, at progression, by examestane and everolimus versus examestane and everolimus followed, at progression, by fulvestrant in postmenopausal women with HR+ and HER2- LABC or MBC whose disease has progressed to NSAI in the adjuvant or metastatic setting.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2015
Typical duration for phase_3
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 26, 2015
CompletedFirst Posted
Study publicly available on registry
March 31, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2019
CompletedJune 15, 2016
June 1, 2016
2.1 years
January 26, 2015
June 14, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS1)
The number of events required for the other primary endpoint (PFS1), and the expected time needed to achieve it are derived from previous calculations. Assuming an average accrual rate of 31 pts/month (677pts/22 months), a median PFS1 of 6 months in the Fulvestrant arm (control), a Hazard ratio of 0.70 (implying that a median PFS1 of 8,6 months is expected in the experimental arm, a 2-sided significance level of 0.025 and power of 0.90, 391 events are required for PFS1, that will be achieved in about 22 months (East 6 software).
Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Total Progression-free survival (PFST)
Overall study size is driven by the endpoint less frequent (PFST). Sample size is planned to identify a Hazard ratio of 0.75, assuming an overall study duration of 36 months, an accrual duration of 24 months, a 2-sided significance level of 0.025 and power of 0.80. Assuming a median PFST of 12 months in the Fulvestrant arm (control), the expected PFST in the experimental arm will be equal to 16 months and 677 subjects need to be enrolled (East 6 software) with an average accrual rate equal to 30.8 patients/month (11 months per year have been considered).
Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Secondary Outcomes (4)
Response Rate
Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Clinical Benefit Rate
Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Overall Survival
Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Safety - 5D5L questionnaire
up to 31 days since last treatment
Study Arms (2)
ARM 1
EXPERIMENTALEverolimus plus Exemestane -\> progression disease (PD) -\> fulvestrant (ARM 1)
ARM 2
EXPERIMENTALFulvestrant -\> progression disease (PD) -\> everolimus plus exemestane (ARM 2)
Interventions
500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter
Eligibility Criteria
You may qualify if:
- Adult women (≥ 18 years of age) with LABC or MBC not amenable to curative treatment by surgery or radiotherapy, refractory to NSAI
- Histological or cytological confirmation of ER+ BC and/or PgR+.
- Postmenopausal women.
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to randomization
- Patients must have:
- At least one lesion that can be accurately measured in at least one dimension ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI
- Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
- Adequate bone marrow and coagulation according RCP
- Adequate liver function, according RCP
- Adequate renal function, according RCP
- ECOG Performance Status ≤ 2
- Written informed consent
You may not qualify if:
- HER2-overexpressing patients by local laboratory testing (IHC3+ staining or in situ hybridization positive).
- Patients who received chemotherapy for MBC
- Patients who received more than one NSAI treatment for LABC or MBC
- Pre-menopausal, pregnant, lactating women.
- Known hypersensitivity to mTOR inhibitors
- Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
- Radiotherapy within four weeks prior to enrollment
- Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
- Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in some cases
- Patients with symptomatic visceral disease in need of urgent disease control
- Symptomatic brain or other CNS metastases.
- Patients with a known history of HIV seropositivity.
- Active, bleeding diathesis, or on oral anti-vitamin K medication (except cases).
- Any severe and / or uncontrolled medical conditions such as:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Consorzio Oncotechlead
- Clinical Research Technology S.r.l.collaborator
Study Sites (41)
ASL19 - Ospedale Cardinal Massaia
Asti, Italy
Azienda Ospedaliera Policlinico di Bari
Bari, Italy
Istituto Tumori Giovanni Paolo II
Bari, Italy
Azienda Ospedaliera "G. Rummo"
Benevento, Italy
Ospedale Fatebenefratelli 'Sacro Cuore di Gesù' di Benevento
Benevento, Italy
A.O. Ospedale Papa Giovanni XXIII
Bergamo, Italy
Presidio Ospedaliero Antonio Perrino
Brindisi, Italy
Azienda Ospedaliera - A. Businco - A.S.L. N. 8
Cagliari, Italy
Fondazione del Piemonte per l' Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.)
Candiolo, Italy
ASL di Taranto - Polo Occidentale
Castellaneta, Italy
A.O.R.N.A.S. Garibaldi Nesima di Catania
Catania, Italy
Fondazione per la Ricerca e la Cura dei Tumori T. Campanella - Campus S. Venuta
Catanzaro, Italy
Azienda Ospedaliera S. Croce e Carle
Cuneo, Italy
Ospedale Infermi di Rimini
Faenza, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, Italy
Azienda Ospedaliero - Universitaria Ospedali Riuniti di Foggia
Foggia, Italy
I.R.C.C.S. A.O.U San Martino - IST
Genova, Italy
Ospedale Civile di guastalla
Guastalla, Italy
Presidio Ospedaliero "Renzetti"
Lanciano, Italy
Ospedale Vito Fazzi
Lecce, Italy
Ospedale Civile San Salvatore - Università degli Studi L'Aquila
L’Aquila, Italy
Ospedale di Macerata
Macerata, Italy
AO Papardo
Messina, Italy
AORN . Ospedali dei colli Monaldi-Cotugno
Napoli, Italy
Azienda Ospedaliera 'A. Cardarelli' (AORN)
Napoli, Italy
Azienda Ospedaliera Universitaria Federico II
Napoli, Italy
Istituto Nazionale per lo studio dei Tumori - Fondazione 'Pascale'
Napoli, Italy
A.O.U. 'Maggiore della Carità'
Novara, Italy
A.O.U.P. 'Paolo Giaccone'
Palermo, Italy
Azienda Ospedaliera S. Chiara
Pisa, Italy
Ospedale F. Lotti
Pontedera, Italy
Ospedale di Ravenna
Ravenna, Italy
Campus Biomedico di Roma
Roma, Italy
Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia A
Roma, Italy
Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia B
Roma, Italy
Azienda Ospedaliera 'San Giovanni di Dio e Ruggi D'Aragona'
Salerno, Italy
IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico 'Casa Sollievo della Sofferenza'
San Giovanni Rotondo, Italy
Azienda Ospedaliera Universitaria di Sassari
Sassari, Italy
Azienda Ospedaliero Universitaria ´S. Maria della Misericordia´ di Udine
Udine, Italy
"Ospedale Borgo Roma Verona Sezione di Oncologia Medica"
Verona, Italy
Ospedale Sacro Cuore Don Calabria di Negrar
Verona, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabino De Placido, MD
Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 26, 2015
First Posted
March 31, 2015
Study Start
December 1, 2015
Primary Completion
January 1, 2018
Study Completion
January 1, 2019
Last Updated
June 15, 2016
Record last verified: 2016-06
Data Sharing
- IPD Sharing
- Will not share