ExclUsive endocRine therapy Or radiation theraPy for women aged ≥70 years with luminal A-like early stage breast cancer (EUROPA): a randomized phase 3 trial

2023-508094-88-00 Protocol EUROPA Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 8 Feb 2021 · Status Ongoing, recruiting · 1 EU/EEA countries · 19 sites · Protocol EUROPA

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 926
Countries 1
Sites 19

breast cancer

- To determine the IBTR rate of exclusive RT as compared to exclusive ET after BCS in low-risk early BC patients aged ≥70 years. - To determine the PROMs HRQoL, as assessed by the QLQ-C30 and module BR45 questionnaires, of exclusive RT as compared to exclusive ET after BCS in low-risk early BC patients aged ≥70 years.

Key facts

Sponsor
University Of Florence
Participant type
Patients
Age range
65+ years
Gender
Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
8 Feb 2021 → ongoing
Decision date (initial)
2023-11-06
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2023-508094-88-00
EudraCT number
2020-000428-21
ClinicalTrials.gov
NCT04134598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

- To determine the IBTR rate of exclusive RT as compared to exclusive ET after BCS in low-risk early BC patients aged ≥70 years.
- To determine the PROMs HRQoL, as assessed by the QLQ-C30 and module BR45 questionnaires, of exclusive RT as compared to exclusive ET after BCS in low-risk early BC patients aged ≥70 years.

Secondary objectives 6

  1. Safety, as assessed by the number and grade of participants with reported AEs.
  2. Individual scales from QLQ-C30 and module QLQ-BR45 scores.
  3. PROMs HRQoL measured by ELD14 questionnaire (optional).
  4. Rate of cosmesis assessment grade.
  5. LRR, CBC, DM rate.
  6. BCSS and OS.

Conditions and MedDRA coding

breast cancer

VersionLevelCodeTermSystem organ class
20.0 PT 10006187 Breast cancer 100000004864

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Women aged ≥70 years
  2. Histologically proven invasive adenocarcinoma of the breast
  3. Pathological T1 (pT1) stage
  4. Postoperative negative (no ink) final surgical margins
  5. Clinical and pathological N0 (cN0 and pN0) stage (isolated tumor cells [i+] allowed)
  6. Any tumor grade (if pT ≤10 mm), G1-2 tumor grade (if pT between 11 and 19 mm)
  7. Luminal A-like biology (immunohistochemistry (IHC)-based on local assessment 50): ER and PgR positive (≥10%); Human epidermal growth factor receptor 2 (HER2) negative (score 0 or 1+ and proven negative by in-situ hybridization [ISH] in case of score 2+); and Ki67 low (≤20%) by IHC staining
  8. Surgically treated with BCS with or without sentinel node biopsy (SNB)
  9. Written informed consent

Exclusion criteria 8

  1. Clinical evidence of DM or LR at baseline
  2. Preoperative systemic treatments (i. e., chemotherapy, endocrine therapy).
  3. Current treatment with any hormonal agents such as tamoxifen, raloxifene, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or BC prevention (patients are eligible if these medications are discontinued prior to randomization).
  4. Known disorders associated with a higher risk for complications following RT such as collagen vascular disease, dermatomyositis, systemic lupus erythematosus or scleroderma.
  5. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  6. Any serious uncontrolled medical disorder, non-malignant systemic disease, or active uncontrolled infection. Examples include but are not limited to uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction or uncontrolled major seizure disorder.
  7. No other cancers in the last 5 years (except basal or squamous cell carcinoma of the skin that has been treated), unless in clinical remission at the time of randomization.
  8. Synchronous diagnosis of bilateral breast cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. IBTR rate at 5 years.
  2. PROMs HRQoL measured by global quality of life score (QLQ-C30) using the GHS at 24 months

Secondary endpoints 9

  1. LRR rate at 5 years
  2. CBC rate at 5 years
  3. DM rate at 5 years
  4. BCSS at 5 years
  5. OS at 5 years
  6. Safety, as assessed by the number and grade of participants with reported AEs at 5 years
  7. Individual scales from QLQ-C30 and QLQ-BR45 scores at baseline, 3, 6, 12, 24 months, and 5 years
  8. Rate of cosmesis assessment grade at baseline, 3, 6, 12, 24 months, and 5 years
  9. PROMs HRQoL measured by ELD14 questionnaire (optional) at baseline, 12, 24 months, and 5 years

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Letrozole

SCP236273 · ATC

Active substance
Letrozole
Route of administration
ORAL
Max daily dose
2.5 mg milligram(s)
Max total dose
2.5 mg milligram(s)
Max treatment duration
60 Month(s)
Authorisation status
Authorised
ATC code
L02BG04 — LETROZOLE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Anastrozole

SCP140009 · ATC

Active substance
Anastrozole
Route of administration
ORAL
Max daily dose
1 mg milligram(s)
Max total dose
1 mg milligram(s)
Max treatment duration
60 Month(s)
Authorisation status
Authorised
ATC code
L02BG03 — ANASTROZOLE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Exemestane

SCP139728 · ATC

Active substance
Exemestane
Route of administration
ORAL
Max daily dose
25 mg milligram(s)
Max total dose
25 mg milligram(s)
Max treatment duration
60 Week(s)
Authorisation status
Authorised
ATC code
L02BG06 — EXEMESTANE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tamoxifen

SCP202373 · ATC

Active substance
Tamoxifen
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
40 mg milligram(s)
Max treatment duration
60 Month(s)
Authorisation status
Authorised
ATC code
L02BA01 — TAMOXIFEN
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Florence

Sponsor organisation
University Of Florence
Address
Viale Giovan Battista Morgagni 50
City
Florence
Postcode
50134
Country
Italy

Scientific contact point

Organisation
University Of Florence
Contact name
Lorenzo Livi

Public contact point

Organisation
University Of Florence
Contact name
Lorenzo Livi

Third parties 1

OrganisationCity, countryDuties
Advice Pharma Group S.r.l.
ORG-100046919
 Milan, Italy On site monitoring, Code 5, Data management, E-data capture

Locations

1 EU/EEA country · 19 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Ongoing, recruiting 926 19
Rest of world — 0 —

Investigational sites

Italy

19 sites · Ongoing, recruiting
University Of Florence
SOD Radioterapia Oncologica AOU Careggi, Viale Giovan Battista Morgagni 50, 50134, Florence
Ospedale Santa Maria Annunziata
Dipartimento Oncologico, Via Dell' Antella 58, 50012, Bagno A Ripoli
IRCCS Ospedale Policlinico San Martino
U.O. Oncologia Radioterapica, Largo Rosanna Benzi 10, 16132, Genoa
Fondazione IRCCS Istituto Nazionale Dei Tumori
S.C. di Radioterapia dei Tumori della Mammella, Via Giacomo Venezian 1, 20133, Milan
Humanitas Research Hospital
U.O. Radioterapia e Radiochirurgia, Via Alessandro Manzoni 56, 20089, Rozzano
Azienda Provinciale Per I Servizi Sanitari
U.O. di Radioterapia Oncologica, Largo Medaglie D'oro 9, 38122, Trento
Centro Di Riferimento Oncologico Di Aviano
SOC Oncologia Radioterapica, Via Franco Gallini 2, 33081, Aviano
Azienda Sanitaria Universitaria Friuli Centrale
Radioterapia Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Piazzale Santa Maria Della Misericordia 15, 33100, Udine
Azienda Ospedaliero Universitaria Di Modena
S.C. di Radioterapia, Largo Del Pozzo 71, 41124, Modena
Universita' Campus Bio-medico Di Roma
U.O.C. Radioterapia Oncologica, Via Alvaro Del Portillo 200, 00128, Rome
I.F.O. Istituti Fisioterapici Ospitalieri
U.O. Oncologia Medica 2, Via Elio Chianesi N 53, 00144, Rome
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Radioterapia Istituto di Candiolo, Strada Provinciale 142 Km 3,95, 10060, Candiolo
Fondazione IRCCS Policlinico San Matteo
SC Radioterapia Oncologica, Viale Camillo Golgi 19, 27100, Pavia
Istituto San Raffaele
Unità Radioterapia, Via Olgettina 58, 20132, Milan
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
S.C. di Radioterapia Oncologica, Via Venezia 16, 15121, Alexandria
Azienda USL Toscana Centro
Reparto di Oncologia Medica, Viale Giovanni Boccaccio 16, 50053, Empoli
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
U.O.C. Radioterapia, Piazzale Spedali Civili 1, 25123, Brescia
European Institute Of Oncology S.r.l.
Divisione di Radioterapia, Via Giuseppe Ripamonti 435, 20141, Milan
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Day Hospital di Radiochemioterapia, Largo Francesco Vito 1, 00168, Rome

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Italy 2021-02-08 2021-02-08

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-09-08 Italy Acceptable
2023-09-22
 2023-11-06
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-05-05 Italy Acceptable
2023-09-22
 2025-05-05

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