CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Anastrozole or Letrozole or Exemestane
* Drug: Anastrozole or Letrozole or Exemestane


Participation Criteria
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Eligibility Criteria
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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: 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sequential administration chemiotherapy, early breast cancer, breast cancer, aromatase inhibitor, adjuvant, post menopausal