CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer (GIM10-CONSENT)

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole or Letrozole or Exemestane; Drug: Anastrozole or Letrozole or Exemestane

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • A.O.U. Federico II
  • Napoli, Italy, 80131
    • Azienda Ospedaliera 'A. Cardarelli' (AORN)
  • Napoli, Italy, 80131
    • Istituto Nazionale dei Tumori - Fondazione G.Pascale
  • AL
    • Casale Monferrato, AL, Italy, 15033
      • Ospedale Santo SpiritoH
  • AN
    • Fabriano, AN, Italy, 60044
      • Ospedale di Rete 'Engles Profili' - A.S.U.R. Area Vasta 2
  • AV
    • Avellino, AV, Italy, 83100
      • A.O. San Giuseppe Moscati
  • BA
    • Bari, BA, Italy, 70124
      • Istituto Tumori 'Giovanni Paolo II' - IRCCS Ospedale Oncologico
  • BG
    • Bergamo, BG, Italy, 24127
      • ASST Papa Giovanni XXIII - Ospedale Papa Giovanni XXIII
    • Treviglio, BG, Italy, 24047
      • Azienda Ospedaliera Treviglio-Caravaggio
  • BN
    • Benevento, BN, Italy, 82100
      • Azienda Ospedaliera G. Rummo
    • Benevento, BN, Italy, 82100
      • Ospedale Fatebenefratelli 'Sacro Cuore di Gesù'
  • BR
    • Brindisi, BR, Italy, 72100
      • Presidio Ospedaliero 'Antonio Perrino'
  • BS
    • Brescia, BS, Italy, 25123
      • ASST Spedali Civili - P.O. Spedali Civili
  • CB
    • Campobasso, CB, Italy, 86100
      • Ospedale Civile di Campobasso - A. Cardarelli
    • Larino, CB, Italy, 80035
      • Ospedale Vietri
  • CH
    • Chieti, CH, Italy, 66100
      • Ospedale Clinicizzato 'S. Annunziata' - Università degli Studi 'G. d'Annunzio'
    • Lanciano, CH, Italy, 66034
      • Ospedale Civile Renzetti
    • Ortona, CH, Italy, 66026
      • Ospedale Civile 'Gaetano Bernabeo'
  • CN
    • Cuneo, CN, Italy, 12100
      • Azienda Ospedaliera S. Croce e Carle
  • CO
    • Como, CO, Italy, 22100
      • ASST Lariana - Ospedale S. Anna
  • CT
    • Catania, CT, Italy, 95126
      • Humanitas Centro Catanese di Oncologia
  • FC
    • Meldola, FC, Italy, 47014
      • IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
  • FE
    • Cona, FE, Italy, 44124
      • Arcispedale S. Anna - A.O.U. di Ferrara
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • IRCCS 'Casa Sollievo della Sofferenza'
  • FI
    • Firenze, FI, Italy, 50134
      • A.O.U. Careggi
  • FR
    • Frosinone, FR, Italy, 03100
      • AUSL di Frosinone - Ospedale Fabrizio Spaziani
    • Sora, FR, Italy, 03039
      • AUSL di Frosinone - Ospedale SS. Trinità
  • GE
    • Genoa, GE, Italy, 16132
      • IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
    • Genova, GE, Italy, 16128
      • E.O. Ospedali Galliera
  • GR
    • Grosseto, GR, Italy, 58100
      • Azienda U.S.L. N. 9 - Ospedale Misericordia
  • IS
    • Isernia, IS, Italy, 86170
      • Azienda Sanitaria Regionale Molise - Ospedale F. Veneziale - Zona di Isernia
  • LE
    • Lecce, LE, Italy, 73100
      • Ospedale Vito Fazzi
  • LT
    • Latina, LT, Italy, 04100
      • A.S.L. LT - Ospedale Santa Maria Goretti
  • LU
    • Lido di Camaiore, LU, Italy, 55041
      • Ospedale Unico Versilia
    • Lucca, LU, Italy, 55100
      • Ospedale San Luca
  • MB
    • Monza, MB, Italy, 20052
      • ASST Monza - Ospedale San Gerardo
  • MC
    • Macerata, MC, Italy, 62100
      • Ospedale di Macerata
  • MI
    • Gorgonzola, MI, Italy, 20064
      • ASST Melegnano e della Martesana - Ospedale Serbelloni
    • Legnano, MI, Italy, 20025
      • ASST Ovest Milanese - Ospedale Nuovo di Legnano
    • Milano, MI, Italy, 20121
      • ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico
    • Milano, MI, Italy, 20141
      • Istituto Europeo di Oncologia (IRCCS)
  • MN
    • Mantova, MN, Italy, 46100
      • Azienda Ospedaliera Carlo Poma
  • MO
    • Modena, MO, Italy, 41124
      • A.O.U. Policlinico Modena
  • PA
    • Palermo, PA, Italy, 90129
      • A.O.U. Policlinico 'Paolo Giaccone'
  • PC
    • Piacenza, PC, Italy, 29121
      • Ospedale 'Guglielmo da Saliceto'
  • PD
    • Padova, PD, Italy, 35128
      • Istituto Oncologico Veneto - I.R.C.C.S.
  • PE
    • Penne, PE, Italy, 65017
      • Ospedale Civile 'San Massimo'
  • PG
    • Città di Castello, PG, Italy, 06012
      • Ospedale Civile di Città di Castello - A.S.L. n. 1
    • Perugia, PG, Italy, 06132
      • Ospedale S. Maria Della Misericordia
  • PI
    • Pisa, PI, Italy, 56126
      • A.O.U. Pisana - Ospedale Santa Chiara
    • Pontedera, PI, Italy, 56025
      • Ospedale Felice Lotti - Azienda USL 5 di Pisa
  • PM
    • Roma, PM, Italy, 00186
      • Policlinico Umberto I
  • PR
    • Parma, PR, Italy, 43100
      • Azienda Ospedaliera Universitaria di Parma
  • PS
    • Fano, PS, Italy, 61032
      • Ospedale Santa Croce - A.O. Ospedali Riuniti Marche Nord
  • PV
    • Pavia, PV, Italy, 27100
      • Fondazione S. Maugeri IRCCS
  • PZ
    • Potenza, PZ, Italy, 85100
      • Azienda Ospedaliera S. Carlo
  • RA
    • Faenza, RA, Italy, 48018
      • Ospedale per gli Infermi
    • Lugo, RA, Italy, 48022
      • Ospedale Umberto I
  • RC
    • Reggio Calabria, RC, Italy, 89125
      • Azienda Ospedaliera Bianchi - Melacrino - Morelli
  • RE
    • Correggio, RE, Italy, 42015
      • Ospedale San Sebastiano
    • Guastalla, RE, Italy, 42016
      • Ospedale Civile di Guastalla
    • Reggio Emilia, RE, Italy, 42123
      • IRCCS A.O. S.Maria Nuova
  • RM
    • Roma, RM, Italy, 00144
      • Istituto Regina Elena per lo studio e la cura dei tumori
    • Roma, RM, Italy, 00144
      • Ospedale S. Eugenio
    • Roma, RM, Italy, 00149
      • Azienda Ospedaliera San Camillo - Forlanini
    • Roma, RM, Italy, 00186
      • Ospedale Fatebenefratelli San Giovanni Calibita - Isola Tiberina
    • Roma, RM, Italy, 00189
      • A.O. S. Andrea - Università 'La Sapienza' - II Facoltà di Medicina e Chirurgia
  • SS
    • Sassari, SS, Italy, 07100
      • Azienda Ospedaliera n. 1 - Annunziata
  • TO
    • Candiolo, TO, Italy, 10060
      • Fondazione del Piemonte per l'Oncologia - IRCC di Candiolo
    • Torino, TO, Italy, 10126
      • Ospedale S. Anna - A.O.U. Città della Salute e della Scienza
    • Torino, TO, Italy, 10126
      • Ospedale S. Anna - Città della salute
  • VA
    • Saronno, VA, Italy, 21047
      • ASST della Valle Olona - Ospedale di Saronno
  • VE
    • Negrar, VE, Italy, 37024
      • Ospedale Sacro Cuore Don Calabria
  • VT
    • Viterbo, VT, Italy, 01100
      • Ospedale Belcolle - AUSL di Viterbo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: ARM A; Adjuvant chemotherapy → Aromatase inhibitors x 5 yrs (sequential arm)	Drug: Anastrozole or Letrozole or Exemestane; Adjuvant chemotherapy → Anastrozole or Letrozole or Exemestane once a day for 5 years (sequential arm); Other Names: Clinical Practice; Drug: Anastrozole or Letrozole or Exemestane; Adjuvant chemotherapy + Anastrozole or Letrozole or Exemestane once a day for 5 years (concurrent arm); Other Names: Experimental arm
Experimental: ARM B; Adjuvant chemotherapy + Aromatase inhibitors x 5 yrs (concurrent arm)	Drug: Anastrozole or Letrozole or Exemestane; Adjuvant chemotherapy → Anastrozole or Letrozole or Exemestane once a day for 5 years (sequential arm); Other Names: Clinical Practice; Drug: Anastrozole or Letrozole or Exemestane; Adjuvant chemotherapy + Anastrozole or Letrozole or Exemestane once a day for 5 years (concurrent arm); Other Names: Experimental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): June 1, 2028
• Study Completion (Anticipated): June 1, 2028

Study Registration Dates

• First Submitted: September 16, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; adjuvant; aromatase inhibitor; early breast cancer; post menopausal; sequential administration chemiotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Anastrozole; Exemestane
• Other Study ID Numbers: GIM10-CONSENT; 2013-001629-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No