MedPath

CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer

Phase 3
Active, not recruiting
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
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ARM AAnastrozole or Letrozole or ExemestaneAdjuvant chemotherapy → Aromatase inhibitors x 5 yrs (sequential arm)
ARM BAnastrozole or Letrozole or ExemestaneAdjuvant chemotherapy + Aromatase inhibitors x 5 yrs (concurrent arm)
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Translational Study: genomic analysisup 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 analysisup 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 analysisup 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)

Ospedale Santo SpiritoH

🇮🇹

Casale Monferrato, AL, Italy

Ospedale di Rete 'Engles Profili' - A.S.U.R. Area Vasta 2

🇮🇹

Fabriano, AN, Italy

A.O. San Giuseppe Moscati

🇮🇹

Avellino, AV, Italy

Istituto Tumori 'Giovanni Paolo II' - IRCCS Ospedale Oncologico

🇮🇹

Bari, BA, Italy

ASST Papa Giovanni XXIII - Ospedale Papa Giovanni XXIII

🇮🇹

Bergamo, BG, Italy

Azienda Ospedaliera Treviglio-Caravaggio

🇮🇹

Treviglio, BG, Italy

Azienda Ospedaliera G. Rummo

🇮🇹

Benevento, BN, Italy

Ospedale Fatebenefratelli 'Sacro Cuore di Gesù'

🇮🇹

Benevento, BN, Italy

Presidio Ospedaliero 'Antonio Perrino'

🇮🇹

Brindisi, BR, Italy

ASST Spedali Civili - P.O. Spedali Civili

🇮🇹

Brescia, BS, Italy

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Ospedale Santo SpiritoH
🇮🇹Casale Monferrato, AL, Italy

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