CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT02918084
- Lead Sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Brief Summary
Breast cancer is the most common form of cancer among women. For patients candidated for adjuvant chemotherapy and endocrine therapy the optimal timing for their has not been clearly defined yet.
- Detailed Description
Breast cancer is the most common form of cancer among women in North America, Europe and Latin America. Because nearly 80% of breast cancers are endocrine-responsive tumors, the majority of patients candidates for adjuvant chemotherapy (CT) are also candidates for endocrine therapy (ET). The optimal timing (i.e. concomitant vs sequential administration) for the integration of these two treatments has not been clearly defined yet.
In patients with hormone receptor positive early stage breast cancer who are candidates to adjuvant chemotherapy and endocrine therapy, the optimal timing for the integration of these two treatment modalities has not been clearly defined yet.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 1000
-
Women with histological diagnosis of invasive breast cancer completely removed by surgery, any T, any N.
-
Postmenopausal status defined by at least one of the following conditions:
-
Aged ≥ 60
-
Aged 45-59 and satisfying one or more of the following criteria:
-
amenorrhea for ≥12 months and intact uterus;
-
amenorrhea for <12 months and follicle-stimulating hormone (FSH) within the postmenopausal range, including:
- pts with hysterectomy
- pts who have received hormone replacement therapy (HRT)
- pts with chemotherapy-induced amenorrhea
-
-
bilateral oophorectomy at any age >18 years.
-
-
Primary tumor positive for Estrogen Receptors (ER) and/or Progesteron receptors (PgR) (≥1% tumor cells positive by immunohistochemistry or ≥ 10 fmol/mg cytosol protein by ligand binding assay).
-
Patients who are prescribed 5 years of endocrine therapy with an aromatase inhibitors (AI)
-
Indication for adjuvant chemotherapy- Patients with HER-2 positive tumors are eligible provided that they are prescribed trastuzumab according to registered schedule.
-
Signed informed consent.
- HRT currently assumed or during the month before randomization
- Recurrent or metastatic disease
- HER-2 positive tumors if treatment with trastuzumab is considered not appropriate/feasible
- Concurrent illness that contraindicate adjuvant endocrine treatment and/or chemotherapy
- Patients who have received Tamoxifen as part of any breast cancer prevention trial
- Previous history of invasive breast cancer or other invasive malignancy within the previous 10 years, other than squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix, adequately cone biopsied
- Concomitant severe disease which would place the patient at unusual risk
- Concurrent treatment with experimental drugs
- Patients treated with systemic investigational drugs within the past 30 days
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ARM A Anastrozole or Letrozole or Exemestane Adjuvant chemotherapy → Aromatase inhibitors x 5 yrs (sequential arm) ARM B Anastrozole or Letrozole or Exemestane Adjuvant chemotherapy + Aromatase inhibitors x 5 yrs (concurrent arm)
- Primary Outcome Measures
Name Time Method Disease- free Survival (DFS) up to 15 years the primary outcome indicator will be the so called DFS, defined as time elapsing between the date of randomization and the date of one of the following events, whichever occurs first, assessed up to 15 years:
* Local Recurrence of disease
* Regional recurrence of disease
* Distant recurrence of disease
* Contralateral invasive or intraductal breast cancer
* Second primary malignancy other than breast
* Death for any cause
- Secondary Outcome Measures
Name Time Method Translational Study: genomic analysis up to 15 years Expression of genes associated with ER and Ki67 expression will be analyzed by Real Time polymerase chain reaction (PCR) on RNA extracted from formalin-fixed paraffin embedded (FFPE) sections of tumors classified as intermediate risk by clinical and pathological variables (stage I-II, G2, hormone receptors positive) and will be correlated with disease free survival.
Overall Survival (OS) time between the date of randomization up to the date of death for any cause, assessed up to 15 years. Translational Study: epigenetic analysis up to 15 years miRNA expression analysis by real time PCR and DNA methylation analysis by pyrosequencing will be assessed on FFPE sections of tumors classified as intermediate risk by clinical and pathological variables (stage I-II, G2, hormone receptors positive)
Translational Study: proteomic analysis up to 15 years The different proteomic profiles identified in FFPE sections of hormone receptors positive G2 tumors will be correlated with DFS
Trial Locations
- Locations (74)
Azienda Ospedaliera S. Croce e Carle
🇮🇹Cuneo, CN, Italy
Ospedale Civile 'Gaetano Bernabeo'
🇮🇹Ortona, CH, Italy
Ospedale di Macerata
🇮🇹Macerata, MC, Italy
Policlinico Umberto I
🇮🇹Roma, PM, Italy
Azienda Ospedaliera S. Carlo
🇮🇹Potenza, PZ, Italy
Ospedale San Sebastiano
🇮🇹Correggio, RE, Italy
Ospedale Belcolle - AUSL di Viterbo
🇮🇹Viterbo, VT, Italy
Arcispedale S. Anna - A.O.U. di Ferrara
🇮🇹Cona, FE, Italy
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
🇮🇹Genoa, GE, Italy
Azienda Sanitaria Regionale Molise - Ospedale F. Veneziale - Zona di Isernia
🇮🇹Isernia, IS, Italy
E.O. Ospedali Galliera
🇮🇹Genova, GE, Italy
Ospedale 'Guglielmo da Saliceto'
🇮🇹Piacenza, PC, Italy
Istituto Europeo di Oncologia (IRCCS)
🇮🇹Milano, MI, Italy
A.O.U. Policlinico 'Paolo Giaccone'
🇮🇹Palermo, PA, Italy
A.O.U. Policlinico Modena
🇮🇹Modena, MO, Italy
Ospedale Civile 'San Massimo'
🇮🇹Penne, PE, Italy
A.O.U. Pisana - Ospedale Santa Chiara
🇮🇹Pisa, PI, Italy
Ospedale Santa Croce - A.O. Ospedali Riuniti Marche Nord
🇮🇹Fano, PS, Italy
Ospedale S. Maria della Misericordia
🇮🇹Perugia, PG, Italy
Ospedale Fatebenefratelli San Giovanni Calibita - Isola Tiberina
🇮🇹Roma, RM, Italy
ASST della Valle Olona - Ospedale di Saronno
🇮🇹Saronno, VA, Italy
Ospedale Umberto I
🇮🇹Lugo, RA, Italy
Ospedale S. Anna - Città della salute
🇮🇹Torino, TO, Italy
Azienda Ospedaliera 'A. Cardarelli' (AORN)
🇮🇹Napoli, Italy
Ospedale Civile di Città di Castello - A.S.L. n. 1
🇮🇹Città di Castello, PG, Italy
Ospedale S. Eugenio
🇮🇹Roma, RM, Italy
Azienda Ospedaliera n. 1 - Annunziata
🇮🇹Sassari, SS, Italy
Fondazione S. Maugeri IRCCS
🇮🇹Pavia, PV, Italy
A.O. San Giuseppe Moscati
🇮🇹Avellino, AV, Italy
ASST Spedali Civili - P.O. Spedali Civili
🇮🇹Brescia, BS, Italy
ASST Lariana - Ospedale S. Anna
🇮🇹Como, CO, Italy
Ospedale di Rete 'Engles Profili' - A.S.U.R. Area Vasta 2
🇮🇹Fabriano, AN, Italy
Ospedale Santo SpiritoH
🇮🇹Casale Monferrato, AL, Italy
Istituto Tumori 'Giovanni Paolo II' - IRCCS Ospedale Oncologico
🇮🇹Bari, BA, Italy
Azienda Ospedaliera G. Rummo
🇮🇹Benevento, BN, Italy
Ospedale Fatebenefratelli 'Sacro Cuore di Gesù'
🇮🇹Benevento, BN, Italy
Presidio Ospedaliero 'Antonio Perrino'
🇮🇹Brindisi, BR, Italy
Ospedale Clinicizzato 'S. Annunziata' - Università degli Studi 'G. d'Annunzio'
🇮🇹Chieti, CH, Italy
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
🇮🇹Meldola, FC, Italy
Ospedale Unico Versilia
🇮🇹Lido di Camaiore, LU, Italy
ASST Monza - Ospedale San Gerardo
🇮🇹Monza, MB, Italy
Azienda Ospedaliera Universitaria di Parma
🇮🇹Parma, PR, Italy
Ospedale per gli Infermi
🇮🇹Faenza, RA, Italy
Ospedale Civile di Guastalla
🇮🇹Guastalla, RE, Italy
IRCCS A.O. S.Maria Nuova
🇮🇹Reggio Emilia, RE, Italy
Ospedale S. Anna - A.O.U. Città della Salute e della Scienza
🇮🇹Torino, TO, Italy
Ospedale Sacro Cuore Don Calabria
🇮🇹Negrar, VE, Italy
Ospedale Civile di Campobasso - A. Cardarelli
🇮🇹Campobasso, CB, Italy
Ospedale Vietri
🇮🇹Larino, CB, Italy
Ospedale Civile Renzetti
🇮🇹Lanciano, CH, Italy
Humanitas Centro Catanese di Oncologia
🇮🇹Catania, CT, Italy
A.O.U. Careggi
🇮🇹Firenze, FI, Italy
AUSL di Frosinone - Ospedale SS. Trinità
🇮🇹Sora, FR, Italy
IRCCS 'Casa Sollievo della Sofferenza'
🇮🇹San Giovanni Rotondo, FG, Italy
Ospedale Vito Fazzi
🇮🇹Lecce, LE, Italy
A.S.L. LT - Ospedale Santa Maria Goretti
🇮🇹Latina, LT, Italy
Azienda Ospedaliera Carlo Poma
🇮🇹Mantova, MN, Italy
Istituto Regina Elena per lo studio e la cura dei tumori
🇮🇹Roma, RM, Italy
Fondazione del Piemonte per l'Oncologia - IRCC di Candiolo
🇮🇹Candiolo, TO, Italy
A.O.U. Federico II
🇮🇹Napoli, Italy
ASST Papa Giovanni XXIII - Ospedale Papa Giovanni XXIII
🇮🇹Bergamo, BG, Italy
Azienda Ospedaliera Treviglio-Caravaggio
🇮🇹Treviglio, BG, Italy
Azienda U.S.L. N. 9 - Ospedale Misericordia
🇮🇹Grosseto, GR, Italy
Ospedale San Luca
🇮🇹Lucca, LU, Italy
ASST Melegnano e della Martesana - Ospedale Serbelloni
🇮🇹Gorgonzola, MI, Italy
ASST Ovest Milanese - Ospedale Nuovo di Legnano
🇮🇹Legnano, MI, Italy
ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico
🇮🇹Milano, MI, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padova, PD, Italy
Ospedale Felice Lotti - Azienda USL 5 di Pisa
🇮🇹Pontedera, PI, Italy
Azienda Ospedaliera Bianchi - Melacrino - Morelli
🇮🇹Reggio Calabria, RC, Italy
A.O. S. Andrea - Università 'La Sapienza' - II Facoltà di Medicina e Chirurgia
🇮🇹Roma, RM, Italy
Istituto Nazionale dei Tumori - Fondazione G.Pascale
🇮🇹Napoli, Italy
AUSL di Frosinone - Ospedale Fabrizio Spaziani
🇮🇹Frosinone, FR, Italy
Azienda Ospedaliera San Camillo - Forlanini
🇮🇹Roma, RM, Italy