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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.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

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
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
Are there results?
None posted in the registry

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
Show all 12Show fewer
  • 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.
Show all 34Show fewer
  • 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

0039089301545

41 sites in 1 country

Italy41 sites, 41 recruiting

  • ASL19 - Ospedale Cardinal Massaia

    Asti

    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

    Not yet recruiting

  • A.O. Ospedale Papa Giovanni XXIII

    Bergamo

    Recruiting

  • Presidio Ospedaliero Antonio Perrino

    Brindisi

    Recruiting

  • Azienda Ospedaliera - A. Businco - A.S.L. N. 8

    Cagliari

    Not yet recruiting

  • Fondazione del Piemonte per l' Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.)

    Candiolo

    Recruiting

  • ASL di Taranto - Polo Occidentale

    Castellaneta

    Not yet recruiting

  • A.O.R.N.A.S. Garibaldi Nesima di Catania

    Catania

    Recruiting

  • Fondazione per la Ricerca e la Cura dei Tumori T. Campanella - Campus S. Venuta

    Catanzaro

    Not yet recruiting

  • Azienda Ospedaliera S. Croce e Carle

    Cuneo

    Recruiting

  • Ospedale Infermi di Rimini

    Faenza

    Recruiting

  • Azienda Ospedaliera Universitaria Careggi

    Florence

    Not yet recruiting

  • Azienda Ospedaliero - Universitaria Ospedali Riuniti di Foggia

    Foggia

    Not yet recruiting

  • I.R.C.C.S. A.O.U San Martino - IST

    Genova

    Recruiting

  • Ospedale Civile di guastalla

    Guastalla

    Recruiting

  • Ospedale Civile San Salvatore - Università degli Studi L'Aquila

    L’Aquila

    Not yet 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

    Recruiting

  • Ospedale di Macerata

    Province of Macerata

    Not yet 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

    Recruiting

  • Azienda Ospedaliera Universitaria di Sassari

    Sassari

    Not yet recruiting

  • Azienda Ospedaliero Universitaria ´S. Maria della Misericordia´ di Udine

    Udine

    Not yet recruiting

  • "Ospedale Borgo Roma Verona Sezione di Oncologia Medica"

    Verona

    Recruiting

  • Ospedale Sacro Cuore Don Calabria di Negrar

    Verona

    Recruiting

Other trials in Italy

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.

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 groups in NCT02404051
Study groupRoleWhat they receive
ARM 1ExperimentalEverolimus plus Exemestane -> progression disease (PD) -> fulvestrant (ARM 1)
Receives: Drug: Everolimus; Drug: Exemestane; Drug: Fulvestrant
ARM 2ExperimentalFulvestrant -> 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.

  1. 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

  2. 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)

  1. 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

  2. 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

  3. 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

  4. Safety - 5D5L questionnaire

    The overall observation period will be divided into three mutually exclusive segments per treatment phase:

    1. 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
    2. 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.

  1. First posted31 Mar 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionJan 2018 (estimated)
  4. Study completionJan 2019 (estimated)

Resources

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)
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Clinical Research Technology (0039089301545), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS1) (time frame: Time elapsed from randomization to progression or death for any cause whichever occurred first assessed up to 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02404051.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2016.

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