Clinical trial • Phase III • Oncology

everolimus for Breast cancer (ER-positive, HER2-negative)

Phase III trial of everolimus for Breast cancer (ER-positive, HER2-negative).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer (ER-positive, HER2-negative)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
26-07-2024
First CTIS Authorization Date
29-08-2024

Trial design

Randomised, test arm: afinitor (everolimus) 5 mg tablets (oral) administered in addition to standard adjuvant endocrine therapy. comparator arm: placebo (oral tablet) plus standard adjuvant endocrine therapy. product metadata lists afinitor with maxdailydoseamount 10 mg and maxtotaldoseamount 1825 mg over a max treatment period of 24 months; exact trial dosing schedule not specified in the submission metadata.-controlled Phase III trial across 52 sites in Belgium, France.

Randomised
Yes
Comparator
Test arm: Afinitor (everolimus) 5 mg tablets (oral) administered in addition to standard adjuvant endocrine therapy. Comparator arm: Placebo (oral tablet) plus standard adjuvant endocrine therapy. Product metadata lists Afinitor with maxDailyDoseAmount 10 mg and maxTotalDoseAmount 1825 mg over a max treatment period of 24 months; exact trial dosing schedule not specified in the submission metadata.
Target Sample Size
1080
Trial Duration For Participant
730

Eligibility

Recruits 1080 Vulnerable population flag is selected. Only adults (female ≥18 years) are eligible. Signed written informed consent is required from the participant. Subject information sheets and informed consent forms (Part 1 and Part 2) are provided in multiple languages (French, English, Dutch, German) as documented in the submission. No assent procedures are described (participants provide their own consent)..

Pregnancy Exclusion
Patient who is pregnant or breast-feeding. Adequate birth control measures should be taken during the study treatment phase.
Vulnerable Population
Vulnerable population flag is selected. Only adults (female ≥18 years) are eligible. Signed written informed consent is required from the participant. Subject information sheets and informed consent forms (Part 1 and Part 2) are provided in multiple languages (French, English, Dutch, German) as documented in the submission. No assent procedures are described (participants provide their own consent).

Inclusion criteria

  • {"criterion_text":"- Female ≥ 18 years of age\n- Adequate hematological function (neutrophil count  2x109/l, platelet count  100x 109/l)\n- Adequate hepatic function: AST and ALT ≤ 2.5 ULN, alkaline phosphatases ≤ 2.5 ULN, total bilirubin ≤ 2 ULN.\n- Adequate renal function: serum creatinine ≤ 1.5 ULN\n- Signed written informed consent.\n- Histologically proven invasive unilateral or bilateral breast cancer (regardless of the morphological subtype)\n- Any T, M0\n- Patient with high risk of relapse\n- ER+ and HER2 negative : Hormone receptor positive is defined as any staining on the primary tumor, HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and FISH or CISH non-amplified]\n- Primary tumor completely resected (deep margins and overlying skin involvement allowed if fully resected)\n- Patients who will begin an adjuvant hormone therapy or have received a maximum of 4 years of adjuvant hormone therapy. Hormone therapy could be either tamoxifen +/- LH-RH agonists, letrozole, anastrozole or exemestane\n- No clinically or radiologically detectable metastases at time of inclusion.\n- WHO Performance status (ECOG) of 0 or 1."}

Exclusion criteria

  • {"criterion_text":"- Any local or regional recurrence or metastatic disease.\n- Patient with chronic infection\n- Uncontrolled diabetes defined as glycated haemoglobin , HbA1c>7%\n- Uncontrolled hypercholesterolemia (cholesterol >300 mg/dl under adequate therapy).\n- Known hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients.\n- Patient with other concurrent severe and/or uncontrolled medical disease or infection which could compromise participation in the study (e.g. patient who regularly require systemic steroids to control co-morbid disease).\n- Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.\n- Any clinical or radiological suspicion of malignant or pre-malignant disease in the contralateral breast.\n- Patients with pN1mi as sole nodal involvement\n- Previous cancer (excepted basal cell carcinoma of the skin or in situ carcinoma of the cervix) in the preceding 5 years, including invasive contralateral breast cancer.\n- Patient already included in another ongoing therapeutic trial involving an unlicensed drug for which follow-up is required.\n- Patient who is pregnant or breast-feeding. Adequate birth control measures should be taken during the study treatment phase.\n- Patient with significantly impaired lung function (e.g. Chronic Obstructive Pulmonary Disease, respiratory insufficiency, Interstitial Lung Disease)\n- Positive serology for HIV infection or hepatitis C.\n- Chronic carrier of HBV (positive Antigen HbsAg positive in the blood)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Disease free survival rate (DFS) after randomisation (disease is defined as local, regional or metastatic relapse, a new contralateral breast cancer, or death from any cause).","definition_or_measurement_approach":"Disease-free survival (DFS) after randomisation; disease defined as local, regional or metastatic relapse, a new contralateral breast cancer, or death from any cause."}

Secondary endpoints

  • {"endpoint_text":"- Efficacy : Overall survival rate (OS) for the whole population\n- Efficacy : DFS and OS for ER+ and PR+ subgroup\n- Efficacy : DFS and OS for the ER+/PR – subgroup\n- Efficacy : EFS\n- Efficacy : DMFS\n- Efficacy : BMFS\n- Efficacy : Secondary cancer\n- Toxicity : CTC-AE scale version 4.0.\n- Biological : Predictive value of mTOR activation markers on DFS: IHC analysis of primary tumor for pS6K and p4EBP\n- Biological : Other translational analyses linking cancer biology with outcomes\n- Other : Quality of life: QLQ C30\n- Other : EFS and DMFS in low risk patients (according to the EPClin score)\n- Other : Sociologic study","definition_or_measurement_approach":"Secondary endpoints include overall survival (OS); disease-free survival (DFS) and OS in subgroups (ER+/PR+ and ER+/PR-); event-free survival (EFS); distant metastasis-free survival (DMFS); bone metastasis-free survival (BMFS); incidence of secondary cancers; toxicity assessed by CTC-AE v4.0; biological/translational analyses including IHC for pS6K and p4EBP; quality of life measured by QLQ-C30; EFS and DMFS in low-risk patients per EPClin score; and a sociologic study."}

Recruitment

Planned Sample Size
1080
Recruitment Window Months
141
Consent Approach
Signed written informed consent is required from each participant. Information sheets and informed consent forms (Part 1 Selection and Part 2 Randomisation) are provided in multiple languages (French, English, Dutch, German) as included in the submission documents. Consent is provided by the adult participant (no assent procedures described).

Geography

Total Number Of Sites
52
Total Number Of Participants
1080

Belgium

Earliest CTIS Part Ii Submission Date
08-08-2024
Latest Decision Or Authorization Date
29-08-2024
Processing Time Days
21
Number Of Sites
8
Number Of Participants
26

Sites

Site Name
CHU Helora
Department Name
Oncologie
Contact Person Name
Vincent RICHARD
Contact Person Email
vincent.richard@hap.be
Site Name
CHR Verviers
Department Name
Oncologie
Contact Person Name
Annelore BARBEAUX
Contact Person Email
annelore.barbeaux@chplt.be
Site Name
Cliniques du Sud-Luxembourg
Department Name
Oncologie
Contact Person Name
Philippe GLORIEUX
Contact Person Email
philippe.glorieux@vivalia.be
Site Name
CHC MontLegia
Department Name
Oncologie
Contact Person Name
Marie-Pascale GRAAS
Contact Person Email
marie-pascale.graas@chc.be
Site Name
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Department Name
Oncologie
Contact Person Name
Lionel D HONDT
Contact Person Email
lionel.dhondt@uclouvain.be
Site Name
Grand Hopital De Charleroi
Department Name
Oncologie
Contact Person Name
Jean-Luc CANON
Contact Person Email
jean-luc.canon@ghdc.be
Site Name
Cliniques Saint Luc
Department Name
Oncologie
Contact Person Name
François DUHOUX
Contact Person Email
francois.duhoux@uclouvain.be
Site Name
Centre Hospitalier D`Ardenne - Forget
Department Name
Oncologie
Contact Person Name
Frédéric FORGET
Contact Person Email
frederic.forget@vivalia.be

France

Earliest CTIS Part Ii Submission Date
08-08-2024
Latest Decision Or Authorization Date
30-08-2024
Processing Time Days
22
Number Of Sites
44
Number Of Participants
1054

Sites

Site Name
Clinique Pasteur
Department Name
Oncologie
Contact Person Name
Mathilde MARTINEZ
Contact Person Email
mmartinez@clinique-pasteur.com
Site Name
Hôpitaux du Leman
Department Name
Oncologie
Contact Person Name
Mansour RASTKHAH
Contact Person Email
mrastkhah@yahoo.fr
Site Name
Centre Oscar Lambret
Department Name
Oncologie
Contact Person Name
Audrey MAILLIEZ
Contact Person Email
a-mailliez@o-lambret.fr
Site Name
Institut Gustave Roussy
Department Name
Oncologie
Contact Person Name
Fabrice ANDRE
Contact Person Email
Fabrice.ANDRE@gustaveroussy.fr
Site Name
Hôpital Américain
Department Name
Oncologie
Contact Person Name
Alain TOLEDANO
Contact Person Email
alain.toledano@gmail.com
Site Name
Centre Hospitalier Public Du Cotentin
Department Name
Oncologie
Contact Person Name
Laure KALUZINSKY
Contact Person Email
l.kaluzinski@ch-cotentin.fr
Site Name
Sainte Catherine Institut Du Cancer Avignon-Provence
Department Name
Oncologie
Contact Person Name
Julien GRENIER
Contact Person Email
j.grenier@isc84.org
Site Name
Hopital Saint Louis
Department Name
Oncologie
Contact Person Name
Sylvie GIACCHETTI
Contact Person Email
sylvie.giacchetti@aphp.fr
Site Name
Centre Hospitalier Jean Rougier
Department Name
Oncologie
Contact Person Name
Nadia DJABALI LEVASSEUR
Contact Person Email
nadia.levasseur@ch-cahors.fr
Site Name
Institut De Cancerologie De Lorraine
Department Name
Oncologie
Contact Person Name
Anne KIEFFER
Contact Person Email
a.kieffer@nancy.unicancer.fr
Site Name
Hôpitaux du Leman
Department Name
Oncologie
Contact Person Name
Francesco DEL PIANO
Site Name
Groupe Hospitalier Bretagne Sud
Department Name
Oncologie
Contact Person Name
Joëlle EGRETEAU
Contact Person Email
j.egreteau@ch-bretagne-sud.fr
Site Name
Clinique Victor Hugo
Department Name
Oncologie
Contact Person Name
Hugues BOURGEOIS
Contact Person Email
h.bourgeois@ilcgroupe.fr
Site Name
CARIO Centre Armoricain de Radiotherapie D'Imagerie medicale et D'Oncologie
Department Name
Oncologie
Contact Person Name
Anne-Claire HARDY-BESSARD
Contact Person Email
ac.hardy@cario-sante.fr
Site Name
Centre Hospitalier Blois Simone Veil
Department Name
Oncologie
Contact Person Name
Olivier ARSENE
Contact Person Email
arseneo@ch-blois.fr
Site Name
Centre Hospitalier de Sens
Department Name
Oncologie
Contact Person Name
Laure CHAUVENET
Contact Person Email
lchauvenet@ch-sens.fr
Site Name
ICO ‐ Centre René Gauducheau
Department Name
Oncologie
Contact Person Name
Mario CAMPONE
Contact Person Email
mario.campone@ico.unicancer.fr
Site Name
CHU Dupuytren
Department Name
Oncologie
Contact Person Name
Laurence VENAT BOUVET
Contact Person Email
laurence.venat@chu-limoges.fr
Site Name
Clinique Claude Bernard
Department Name
Oncologie
Contact Person Name
Philippe HOUYAU
Site Name
Centre Hospitalier De Bourg-En-Bresse
Department Name
Oncologie
Contact Person Name
Hubert ORFEUVRE
Contact Person Email
horfeuvre@ch-bourg01.fr
Site Name
Les Hopitaux De Chartres
Department Name
Oncologie
Contact Person Name
David SOLUB
Contact Person Email
dsolub@ch-chartres.fr
Site Name
Groupe Hospitalier Diaconesses Croix Saint Simon
Department Name
Oncologie
Contact Person Name
Catherine DELBALDO
Contact Person Email
CDelbaldo@hopital-dcss.org
Site Name
Centre Jean Perrin
Department Name
Oncologie
Contact Person Name
Marie-Ange MOURET-REYNIER
Site Name
Institut Curie (Saint-Cloud)
Department Name
Oncologie
Contact Person Name
Etienne BRAIN
Contact Person Email
etienne.brain@curie.fr
Site Name
Institut Godinot
Department Name
Oncologie
Contact Person Name
Christelle JOUANNAUD
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
Oncologie
Contact Person Name
Jean-Philippe JACQUIN
Site Name
Institut Bergonie
Department Name
Oncologie
Contact Person Name
Marc DEBLED
Contact Person Email
m.debled@bordeaux.unicancer.fr
Site Name
Hopital Prive Drome-Ardeche
Department Name
Oncologie
Contact Person Name
Hugues BARLETTA
Contact Person Email
dr.barletta@wanadoo.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie
Contact Person Name
Mario CAMPONE
Contact Person Email
mario.campone@ico.unicancer.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncologie
Contact Person Name
Philippe BARTHELEMY
Contact Person Email
p.barthelemy@icans.eu
Site Name
Centre Hospitalier Annecy Genevois
Department Name
Oncologie
Contact Person Name
Laëtitia STEFANI
Contact Person Email
lstefani@ch-annecygenevois.fr
Site Name
Institut Curie (26 Rue D Ulm)
Department Name
Oncologie
Contact Person Name
Paul Henri COTTU
Contact Person Email
paul.cottu@curie.fr
Site Name
Centre Hospitalier Intercommunal De Cornouaille
Department Name
Oncologie
Contact Person Name
Delphine MOLLON-GRANGE
Contact Person Email
d.mollon@ch-cornouaille.fr
Site Name
Clinique De La Sauvegarde
Department Name
Oncologie
Contact Person Name
Isabelle MOULLET
Contact Person Email
i.moullet@wanadoo.fr
Site Name
Hopital Ambroise Pare
Department Name
Oncologie
Contact Person Name
Véronique BRUNEL
Contact Person Email
V.BRUNEL@hopital-europeen.fr
Site Name
Oncopole Claudius Regaud
Department Name
Oncologie
Contact Person Name
Florence DALENC
Site Name
Clinique Croix du Sud
Department Name
Oncologie
Contact Person Name
Anne-Pascale LAURENTY
Site Name
Groupement Hospitalier Portes De Provence
Department Name
Oncologie
Contact Person Name
Blaha BELGADI
Contact Person Email
blaha.belgadi@ch-montelimar.fr
Site Name
Centre Hospitalier Intercommunal Creteil
Department Name
Oncologie
Contact Person Name
Emmanuelle MALAURIE AGOSTINI
Site Name
Centre Leon Berard
Department Name
Oncologie
Contact Person Name
Thomas BACHELOT
Site Name
Oncoradio Centre Oncogard
Department Name
Oncologie
Contact Person Name
Eric LEGOUFFE
Contact Person Email
legouffe.oncogard@orange.fr
Site Name
Centr Georges Francois Leclerc
Department Name
Oncologie
Contact Person Name
Isabelle DESMOULINS
Contact Person Email
idesmoulins@cgfl.fr
Site Name
Hopital Tenon
Department Name
Oncologie
Contact Person Name
Sandrine RICHARD
Contact Person Email
sandrine.richard@tnn.aphp.fr
Site Name
Centre Francois Baclesse
Department Name
Oncologie
Contact Person Name
Djelila ALLOUACHE
Site Name
Centre Hospitalier De Bourg-En-Bresse
Department Name
Oncologie
Contact Person Name
Hubert ORFEUVRE
Contact Person Email
horfeuvre@ch-bourg01.fr
Site Name
Les Hopitaux De Chartres
Department Name
Oncologie
Contact Person Name
David SOLUB
Contact Person Email
dsolub@ch-chartres.fr
Site Name
Groupe Hospitalier Diaconesses Croix Saint Simon
Department Name
Oncologie
Contact Person Name
Catherine DELBALDO
Contact Person Email
CDelbaldo@hopital-dcss.org
Site Name
Institut Curie (35 Rue Dailly)
Department Name
Oncologie
Contact Person Name
Etienne BRAIN
Contact Person Email
etienne.brain@curie.fr
Site Name
Clinique De La Sauvegarde (Lyon)
Department Name
Oncologie
Contact Person Name
Isabelle MOULLET
Contact Person Email
i.moullet@wanadoo.fr
Site Name
Hopital Ambroise Pare (Marseille)
Department Name
Oncologie
Contact Person Name
Véronique BRUNEL
Contact Person Email
V.BRUNEL@hopital-europeen.fr

Sponsor

Primary sponsor

Full Name
Unicancer
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
Afinitor 5 mg tablets
Active Substance
everolimus
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (EU/1/09/538/001)
Maximum Dose
10 mg per day (maxDailyDoseAmount)
Investigational Product Name
PLACEBO
Active Substance
placebo
Modality
Other
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
0 mg (maxDailyDoseAmount)
Combination Treatment
Yes

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