Fulvestrant and EVerolimus Plus EXemestane in Metastatic Breast Cancer

NCT ID: NCT02404051

Last Updated: 2016-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

745 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2019-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Metastatic Breast Cancer Breast Cancer Hormone Receptor Positive Tumor Human Epidermal Growth Factor 2 Negative Carcinoma of Breast Locally Advanced Malignant Neoplasm

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ARM 1

Everolimus plus Exemestane -\> progression disease (PD) -\> fulvestrant (ARM 1)

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

10 mg daily tablets

Exemestane

Intervention Type DRUG

25 mg daily tablets

Fulvestrant

Intervention Type DRUG

500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter

ARM 2

Fulvestrant -\> progression disease (PD) -\> everolimus plus exemestane (ARM 2)

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

10 mg daily tablets

Exemestane

Intervention Type DRUG

25 mg daily tablets

Fulvestrant

Intervention Type DRUG

500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Everolimus

10 mg daily tablets

Intervention Type DRUG

Exemestane

25 mg daily tablets

Intervention Type DRUG

Fulvestrant

500 mg i.m. on Days 1, 15 and 29 and every 28 days thereafter

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Afinitor Aromasin Faslodex

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Adult women (≥ 18 years of age) with LABC or MBC not amenable to curative treatment by surgery or radiotherapy, refractory to NSAI
2. Histological or cytological confirmation of ER+ BC and/or PgR+.
3. Postmenopausal women.
4. Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to randomization
5. 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.
6. Adequate bone marrow and coagulation according RCP
7. Adequate liver function, according RCP
8. Adequate renal function, according RCP
9. ECOG Performance Status ≤ 2
10. Written informed consent

Exclusion Criteria

1. HER2-overexpressing patients by local laboratory testing (IHC3+ staining or in situ hybridization positive).
2. Patients who received chemotherapy for MBC
3. Patients who received more than one NSAI treatment for LABC or MBC
4. Pre-menopausal, pregnant, lactating women.
5. Known hypersensitivity to mTOR inhibitors
6. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
7. Radiotherapy within four weeks prior to enrollment
8. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
9. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in some cases
10. Patients with symptomatic visceral disease in need of urgent disease control
11. Symptomatic brain or other CNS metastases.
12. Patients with a known history of HIV seropositivity.
13. Active, bleeding diathesis, or on oral anti-vitamin K medication (except cases).
14. 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.

* 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
16. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
17. History of non-compliance to medical regimens.
18. 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Clinical Research Technology S.r.l.

INDUSTRY

Sponsor Role collaborator

Consorzio Oncotech

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sabino De Placido, MD

Role: PRINCIPAL_INVESTIGATOR

Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

ASL19 - Ospedale Cardinal Massaia

Asti, , Italy

Site Status RECRUITING

Azienda Ospedaliera Policlinico di Bari

Bari, , Italy

Site Status NOT_YET_RECRUITING

Istituto Tumori Giovanni Paolo II

Bari, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera "G. Rummo"

Benevento, , Italy

Site Status NOT_YET_RECRUITING

Ospedale Fatebenefratelli 'Sacro Cuore di Gesù' di Benevento

Benevento, , Italy

Site Status NOT_YET_RECRUITING

A.O. Ospedale Papa Giovanni XXIII

Bergamo, , Italy

Site Status RECRUITING

Presidio Ospedaliero Antonio Perrino

Brindisi, , Italy

Site Status RECRUITING

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

Cagliari, , Italy

Site Status NOT_YET_RECRUITING

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

Candiolo, , Italy

Site Status RECRUITING

ASL di Taranto - Polo Occidentale

Castellaneta, , Italy

Site Status NOT_YET_RECRUITING

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

Catania, , Italy

Site Status RECRUITING

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

Catanzaro, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera S. Croce e Carle

Cuneo, , Italy

Site Status RECRUITING

Ospedale Infermi di Rimini

Faenza, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliero - Universitaria Ospedali Riuniti di Foggia

Foggia, , Italy

Site Status NOT_YET_RECRUITING

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

Genova, , Italy

Site Status RECRUITING

Ospedale Civile di guastalla

Guastalla, , Italy

Site Status RECRUITING

Presidio Ospedaliero "Renzetti"

Lanciano, , Italy

Site Status RECRUITING

Ospedale Vito Fazzi

Lecce, , Italy

Site Status RECRUITING

Ospedale Civile San Salvatore - Università degli Studi L'Aquila

L’Aquila, , Italy

Site Status NOT_YET_RECRUITING

Ospedale di Macerata

Macerata, , Italy

Site Status NOT_YET_RECRUITING

AO Papardo

Messina, , Italy

Site Status RECRUITING

AORN . Ospedali dei colli Monaldi-Cotugno

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliera 'A. Cardarelli' (AORN)

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Federico II

Napoli, , Italy

Site Status RECRUITING

Istituto Nazionale per lo studio dei Tumori - Fondazione 'Pascale'

Napoli, , Italy

Site Status RECRUITING

A.O.U. 'Maggiore della Carità'

Novara, , Italy

Site Status RECRUITING

A.O.U.P. 'Paolo Giaccone'

Palermo, , Italy

Site Status RECRUITING

Azienda Ospedaliera S. Chiara

Pisa, , Italy

Site Status RECRUITING

Ospedale F. Lotti

Pontedera, , Italy

Site Status RECRUITING

Ospedale di Ravenna

Ravenna, , Italy

Site Status RECRUITING

Campus Biomedico di Roma

Roma, , Italy

Site Status RECRUITING

Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia A

Roma, , Italy

Site Status RECRUITING

Istituto Regina Elena per lo studio e la cura dei tumori - Oncologia B

Roma, , Italy

Site Status RECRUITING

Azienda Ospedaliera 'San Giovanni di Dio e Ruggi D'Aragona'

Salerno, , Italy

Site Status RECRUITING

IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico 'Casa Sollievo della Sofferenza'

San Giovanni Rotondo, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria di Sassari

Sassari, , Italy

Site Status NOT_YET_RECRUITING

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

Udine, , Italy

Site Status NOT_YET_RECRUITING

"Ospedale Borgo Roma Verona Sezione di Oncologia Medica"

Verona, , Italy

Site Status RECRUITING

Ospedale Sacro Cuore Don Calabria di Negrar

Verona, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Clinical Research Technology

Role: CONTACT

0039089301545

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014-004035-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GIM16-FEVEX

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

500mg Fulvestrant in HR+ MBC
NCT03708432 COMPLETED