Metastatic Breast CancerPhase 3FEVEXNCT02404051
Fulvestrant and EVerolimus Plus EXemestane in Metastatic Breast Cancer
A Phase 3 study testing Everolimus, Exemestane and Fulvestrant in people with Metastatic Breast Cancer and Breast Cancer, run by Consorzio Oncotech at 41 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, Breast Cancer, Hormone Receptor Positive Tumor
- What is being tested?
- Everolimus, Exemestane and Fulvestrant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 745 participants
- Where
- 41 sitesItaly
- Study dates
- Dec 2015to Jan 2019
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN
- Acute and chronic, active infectious disorders
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatments (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
- Inability to swallow oral medications
- Significant symptomatic deterioration of lung function.
- Hepatic-related exclusion criteria:
- History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
- Presence of Hepatitis B surface antigen (HbsAg) and/or of Hepatitis B Virus - Deoxyribonucleic acid (HBV-DNA)
- Presence of anti-HCV and/or HCV-RNA-PCR
- History of, or current alcohol misuse/abuse within the past 12 months
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment.
- History of non-compliance to medical regimens.
- Patients unwilling to or unable to comply with the protocol
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
- History of non-compliance to medical regimens.
- Patients unwilling to or unable to comply with the protocol.
- Screening for hepatitis B
- Prior to enrollment, peculiar patients should be tested for hepatitis B viral load and serologic markers, that is, HBV-DNA, HBsAg, HBsAb, and HBcAb:
- Screening for hepatitis C Patients with any of the following risk factors for hepatitis C should be tested
Trial locations and contacts
41 sites in 1 country.
Clinical Research Technology contact
41 sites in 1 country
Italy41 sites, 41 recruiting
- Recruiting
ASL19 - Ospedale Cardinal Massaia
Asti
- Not yet recruiting
Azienda Ospedaliera Policlinico di Bari
Bari
- Not yet recruiting
Istituto Tumori Giovanni Paolo II
Bari
- Not yet recruiting
Azienda Ospedaliera "G. Rummo"
Benevento
- Not yet recruiting
Ospedale Fatebenefratelli 'Sacro Cuore di Gesù' di Benevento
Benevento
- Recruiting
A.O. Ospedale Papa Giovanni XXIII
Bergamo
- Recruiting
Presidio Ospedaliero Antonio Perrino
Brindisi
- Not yet recruiting
Azienda Ospedaliera - A. Businco - A.S.L. N. 8
Cagliari
- Recruiting
Fondazione del Piemonte per l' Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.)
Candiolo
- Not yet recruiting
ASL di Taranto - Polo Occidentale
Castellaneta
- Recruiting
A.O.R.N.A.S. Garibaldi Nesima di Catania
Catania
- Not yet recruiting
Fondazione per la Ricerca e la Cura dei Tumori T. Campanella - Campus S. Venuta
Catanzaro
- Recruiting
Azienda Ospedaliera S. Croce e Carle
Cuneo
- Recruiting
Ospedale Infermi di Rimini
Faenza
- Not yet recruiting
Azienda Ospedaliera Universitaria Careggi
Florence
- Not yet recruiting
Azienda Ospedaliero - Universitaria Ospedali Riuniti di Foggia
Foggia
- Recruiting
I.R.C.C.S. A.O.U San Martino - IST
Genova
- Recruiting
Ospedale Civile di guastalla
Guastalla
- Not yet recruiting
Ospedale Civile San Salvatore - Università degli Studi L'Aquila
L’Aquila
- Recruiting
Presidio Ospedaliero "Renzetti"
Lanciano
- Recruiting
Ospedale Vito Fazzi
Lecce
- Recruiting
AO Papardo
Messina
- Recruiting
AORN . Ospedali dei colli Monaldi-Cotugno
Naples
- Recruiting
Azienda Ospedaliera 'A. Cardarelli' (AORN)
Naples
- Recruiting
Azienda Ospedaliera Universitaria Federico II
Naples
- Recruiting
Istituto Nazionale per lo studio dei Tumori - Fondazione 'Pascale'
Naples
- Recruiting
A.O.U. 'Maggiore della Carità'
Novara
- Recruiting
A.O.U.P. 'Paolo Giaccone'
Palermo
- Recruiting
Azienda Ospedaliera S. Chiara
Pisa
- Recruiting
Ospedale F. Lotti
Pontedera
- Not yet recruiting
Ospedale di Macerata
Province of Macerata
- Recruiting
Ospedale di Ravenna
Ravenna
- Recruiting
Campus Biomedico di Roma
Roma
- Recruiting
Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia A
Roma
- Recruiting
Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia B
Roma
- Recruiting
Azienda Ospedaliera 'San Giovanni di Dio e Ruggi D'Aragona'
Salerno
- Recruiting
IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico 'Casa Sollievo della Sofferenza'
San Giovanni Rotondo
- Not yet recruiting
Azienda Ospedaliera Universitaria di Sassari
Sassari
- Not yet recruiting
Azienda Ospedaliero Universitaria ´S. Maria della Misericordia´ di Udine
Udine
- Recruiting
"Ospedale Borgo Roma Verona Sezione di Oncologia Medica"
Verona
- Recruiting
Ospedale Sacro Cuore Don Calabria di Negrar
Verona
About this study
Official title: 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
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.
Read the detailed description
In this study everolimus will be administered in combination with exemestane, which is an irreversible steroidal aromatase inactivator that has demonstrated efficacy in the treatment of postmenopausal patients with ABC. Exemestane is indicated for adjuvant treatment of postmenopausal women with HR+ EBC who have received two to three years of tamoxifen and are switched to exemestane for completion of a total of five consecutive years of adjuvant hormonal therapy. It is also indicated for the treatment of ABC in postmenopausal women whose disease has progressed following tamoxifen therapy (in the USA) or following antiestrogen therapy (in Europe). In 2011, the BOLERO-2 trial reported (5; 33) a significant benefit for HR+ HER2- postmenopausal pretreated women in the ABC setting by combining everolimus with exemestane. In this randomized, double-blind, placebo-controlled trial a statistically significant improvement in PFS by adding everolimus to exemestane versus exemestane alone was reported. Adding everolimus determined a 2.4-fold prolongation in PFS from 3.2 up to 7.4 months and so lowered the risk of cancer progression by 56% for these women. These findings were confirmed by an independent assessment (4.1 vs. 11.0 months, risk reduction: 64%). The QoL data shows positive trend in the everolimus plus exemestane treatment arm.
- Conditions
- Metastatic Breast Cancer, Breast Cancer, Hormone Receptor Positive Tumor, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Locally Advanced Malignant Neoplasm
- Being tested
- Everolimus, Exemestane, Fulvestrant
- Keywords
- Breast cancer, HER2Negative, hormone receptor positive (HR+), Metastatic, Locally Advanced, fulvestrant, everolimus, exemestane
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Afinitor
10 mg daily tablets
ExemestaneDrug
Also called Aromasin
25 mg daily tablets
FulvestrantDrug
Also called Faslodex
500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter
| Study group | Role | What they receive |
|---|---|---|
| ARM 1 | Experimental | Everolimus plus Exemestane -> progression disease (PD) -> fulvestrant (ARM 1) Receives: Drug: Everolimus; Drug: Exemestane; Drug: Fulvestrant |
| ARM 2 | Experimental | Fulvestrant -> progression disease (PD) -> everolimus plus exemestane (ARM 2) Receives: Drug: Everolimus; Drug: Exemestane; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Secondary outcomes (4)
Response Rate
Objective Response Rate (ORR), the Clinical Benefit, the overall survival, and the safety profile and the QOLof of the sequence of fulvestrant followed, at progression by exemestane and everolimus versus the sequence of examestane and everolimus followed, at progression, by fulvestrant in postmenopausal women with HR + and HER2- LABC or MBC previously treated with NSAI in the adjuvant or metastatic setting.
Measured: Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Clinical Benefit Rate
Objective Response Rate (ORR), the Clinical Benefit, the overall survival, and the safety profile and the QOLof of the sequence of fulvestrant followed, at progression by exemestane and everolimus versus the sequence of examestane and everolimus followed, at progression, by fulvestrant in postmenopausal women with HR + and HER2- LABC or MBC previously treated with NSAI in the adjuvant or metastatic setting.
Measured: Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Overall Survival
Objective Response Rate (ORR), the Clinical Benefit, the overall survival, and the safety profile and the QOLof of the sequence of fulvestrant followed, at progression by exemestane and everolimus versus the sequence of examestane and everolimus followed, at progression, by fulvestrant in postmenopausal women with HR + and HER2- LABC or MBC previously treated with NSAI in the adjuvant or metastatic setting.
Measured: Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months
Safety - 5D5L questionnaire
The overall observation period will be divided into three mutually exclusive segments per treatment phase:
- pre-treatment period: from day of patient's informed consent to the day before first dose of study medication (phase 1) on-treatment period: from day of first dose of study medication to 30 days (minimum washout) after last dose of study medication (phase 2) or first dose of second phase treatment after cross-over
- post-treatment period: starting at day 31 after last dose of study medication (phase 2)
Measured: up to 31 days since last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startDec 2015
- Primary completionJan 2018 (estimated)
- Study completionJan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 745 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Consorzio Oncotech
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Research Technology S.r.l.
- Responsible party
- Sponsor
- Investigators
- Sabino De Placido, MD, Principal investigator, Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02404051
- Sponsor's protocol ID
- GIM16-FEVEX
- Other IDs
- 2014-004035-38, 2014
- Acronym
- FEVEX
- Status last verified
- Jun 2016
- First submitted
- 26 Jan 2015
- Last updated
- 15 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No