CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer

Breast Cancer Clinical Trial

— GIM10-CONSENT  

Official title:

A Phase III Study Comparing the Concurrent Versus the Sequential Administration of Chemotherapy and Aromatase Inhibitors, as Adjuvant Treatment of Post-menopausal Patients With Endocrine-responsive Early Breast Cancer.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02918084
• Other study ID #: GIM10-CONSENT
• Secondary ID: 2013-001629-23
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2013
• Est. completion date: June 2028

Study information

• Verified date: May 2024
• Source: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Est. completion date: June 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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:

1. Aged = 60

2. 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

3. 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Anastrozole or Letrozole or Exemestane
Adjuvant chemotherapy ? Anastrozole or Letrozole or Exemestane once a day for 5 years (sequential arm)
• Anastrozole or Letrozole or Exemestane
Adjuvant chemotherapy + Anastrozole or Letrozole or Exemestane once a day for 5 years (concurrent arm)

Locations

Country	Name	City	State
Italy	A.O. San Giuseppe Moscati	Avellino	AV
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	ASST Papa Giovanni XXIII - Ospedale Papa Giovanni XXIII	Bergamo	BG
Italy	ASST Spedali Civili - P.O. Spedali Civili	Brescia	BS
Italy	Presidio Ospedaliero 'Antonio Perrino'	Brindisi	BR
Italy	Ospedale Civile di Campobasso - A. Cardarelli	Campobasso	CB
Italy	Fondazione del Piemonte per l'Oncologia - IRCC di Candiolo	Candiolo	TO
Italy	Ospedale Santo SpiritoH	Casale Monferrato	AL
Italy	Humanitas Centro Catanese di Oncologia	Catania	CT
Italy	Ospedale Clinicizzato 'S. Annunziata' - Università degli Studi 'G. d'Annunzio'	Chieti	CH
Italy	Ospedale Civile di Città di Castello - A.S.L. n. 1	Città di Castello	PG
Italy	ASST Lariana - Ospedale S. Anna	Como	CO
Italy	Arcispedale S. Anna - A.O.U. di Ferrara	Cona	FE
Italy	Ospedale San Sebastiano	Correggio	RE
Italy	Azienda Ospedaliera S. Croce e Carle	Cuneo	CN
Italy	Ospedale di Rete 'Engles Profili' - A.S.U.R. Area Vasta 2	Fabriano	AN
Italy	Ospedale per gli Infermi	Faenza	RA
Italy	Ospedale Santa Croce - A.O. Ospedali Riuniti Marche Nord	Fano	PS
Italy	A.O.U. Careggi	Firenze	FI
Italy	AUSL di Frosinone - Ospedale Fabrizio Spaziani	Frosinone	FR
Italy	IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy	Genoa	GE
Italy	E.O. Ospedali Galliera	Genova	GE
Italy	ASST Melegnano e della Martesana - Ospedale Serbelloni	Gorgonzola	MI
Italy	Azienda U.S.L. N. 9 - Ospedale Misericordia	Grosseto	GR
Italy	Ospedale Civile di Guastalla	Guastalla	RE
Italy	Azienda Sanitaria Regionale Molise - Ospedale F. Veneziale - Zona di Isernia	Isernia	IS
Italy	Ospedale Civile Renzetti	Lanciano	CH
Italy	Ospedale Vietri	Larino	CB
Italy	A.S.L. LT - Ospedale Santa Maria Goretti	Latina	LT
Italy	Ospedale Vito Fazzi	Lecce	LE
Italy	ASST Ovest Milanese - Ospedale Nuovo di Legnano	Legnano	MI
Italy	Ospedale Unico Versilia	Lido di Camaiore	LU
Italy	Ospedale San Luca	Lucca	LU
Italy	Ospedale Umberto I	Lugo	RA
Italy	Ospedale di Macerata	Macerata	MC
Italy	Azienda Ospedaliera Carlo Poma	Mantova	MN
Italy	IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)	Meldola	FC
Italy	ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico	Milano	MI
Italy	Istituto Europeo di Oncologia (IRCCS)	Milano	MI
Italy	A.O.U. Policlinico Modena	Modena	MO
Italy	ASST Monza - Ospedale San Gerardo	Monza	MB
Italy	A.O.U. Federico II	Napoli
Italy	Azienda Ospedaliera 'A. Cardarelli' (AORN)	Napoli
Italy	Istituto Nazionale dei Tumori - Fondazione G.Pascale	Napoli
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	VE
Italy	Ospedale Civile 'Gaetano Bernabeo'	Ortona	CH
Italy	Istituto Oncologico Veneto - I.R.C.C.S.	Padova	PD
Italy	A.O.U. Policlinico 'Paolo Giaccone'	Palermo	PA
Italy	Azienda Ospedaliera Universitaria di Parma	Parma	PR
Italy	Fondazione S. Maugeri IRCCS	Pavia	PV
Italy	Ospedale Civile 'San Massimo'	Penne	PE
Italy	Ospedale S. Maria della Misericordia	Perugia	PG
Italy	Ospedale 'Guglielmo da Saliceto'	Piacenza	PC
Italy	A.O.U. Pisana - Ospedale Santa Chiara	Pisa	PI
Italy	Ospedale Felice Lotti - Azienda USL 5 di Pisa	Pontedera	PI
Italy	Azienda Ospedaliera S. Carlo	Potenza	PZ
Italy	Azienda Ospedaliera Bianchi - Melacrino - Morelli	Reggio Calabria	RC
Italy	IRCCS A.O. S.Maria Nuova	Reggio Emilia	RE
Italy	A.O. S. Andrea - Università 'La Sapienza' - II Facoltà di Medicina e Chirurgia	Roma	RM
Italy	Azienda Ospedaliera San Camillo - Forlanini	Roma	RM
Italy	Istituto Regina Elena per lo studio e la cura dei tumori	Roma	RM
Italy	Ospedale Fatebenefratelli San Giovanni Calibita - Isola Tiberina	Roma	RM
Italy	Ospedale S. Eugenio	Roma	RM
Italy	Policlinico Umberto I	Roma	PM
Italy	IRCCS 'Casa Sollievo della Sofferenza'	San Giovanni Rotondo	FG
Italy	ASST della Valle Olona - Ospedale di Saronno	Saronno	VA
Italy	Azienda Ospedaliera n. 1 - Annunziata	Sassari	SS
Italy	AUSL di Frosinone - Ospedale SS. Trinità	Sora	FR
Italy	Ospedale S. Anna - A.O.U. Città della Salute e della Scienza	Torino	TO
Italy	Ospedale S. Anna - Città della salute	Torino	TO
Italy	Azienda Ospedaliera Treviglio-Caravaggio	Treviglio	BG
Italy	Ospedale Belcolle - AUSL di Viterbo	Viterbo	VT

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy	Clinical Research Technology S.r.l.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease- free Survival (DFS)	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	up to 15 years
Secondary	Overall Survival (OS)		time between the date of randomization up to the date of death for any cause, assessed up to 15 years.
Secondary	Translational Study: genomic analysis	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.	up to 15 years
Secondary	Translational Study: epigenetic analysis	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)	up to 15 years
Secondary	Translational Study: proteomic analysis	The different proteomic profiles identified in FFPE sections of hormone receptors positive G2 tumors will be correlated with DFS	up to 15 years