Patients with newly, untreated, resectable HR+/HER2- eBCs, suitable for pre-operative therapy with anastrozole MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: VESANOID - 100 CAPSULE MOLLI 10 MG IN FLACONE IN VETRO
Product Name: VESANOID
Product Code: ATRA
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: TRETINOINA
Current Sponsor code: AT
Sponsors
IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed, informed consent 2. Histologically confirmed non-metastatic operable primary invasive HR-positive breast cancer subjected to diagnostic core biopsy 3. Menopausal status 4. HR-positive/HER2-negative eBC defined as - ER>1% on immunohistochemistry (IHC) staining - HER2 score equal to 0, 1+, 2+ (if FISH neg) on IHC staining 5. Available paraffin-embedded tumor block (FFPE) taken at diagnostic biopsy for Ki67 determination (IHC) 6. Adequate bone marrow, hepatic and renal function including the following a. Hb = 9.0 g/dL, absolute neutrophil count = 1.5 x 109/L, platelets =100 x 109/L b. Total bilirubin = 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome c. AST (SGOT), ALT (SGPT) = 2.5 x upper normal limit (or 5x UNL in the presence of liver metastases) d. Creatinine = 1.5 x upper normal limit 7. Age = 18 years 8. Performance status (PS) = 1 (ECOG scale). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 51 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 61
Exclusion criteria
Exclusion criteria: 1. Presence of metastatic disease 2. Pre-menopausal status 3. Previous investigational treatment for any condition within 4 weeks of randomization date 4. Treatment including radiation therapy, chemotherapy, biotherapy and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry 5. Co-existing active infection or serious concurrent illness 6. Any medical or other condition that in the Investigator’s opinion renders the patient unsuitable for this study due to unacceptable risk 7. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies 8. Gastrointestinal disorders that may interfere with absorption of the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the pre-operative activity of ATRA in combination with anastrozole vs. anastrozole alone in operable HR+/HER2- eBCs, via assessment of the proliferative arrest of BC cells (Ki67 level <2.7%).;Secondary Objective: 1.To assess the activity of ATRA according to the % of Ki67 reduction, measured before and after treatment. 2.To assess the activity of ATRA in terms of tumor size reduction and response rate, according to the RECIST criteria, after 4 weeks of therapy. 3.To validate the predictive power of ATRA-21, a gene-expression model associated with ATRA activity. 4.To assess the safety and tolerability of ATRA administrated daily p.o. for 4 weeks in combination with anastrozole.;Primary end point(s): to investigate the primary objective, we will compare the proportion of responder patients in the 2 arm (Aa vs. a) according to the Ki67 assessment, measured at baseline and after treatment.;Timepoint(s) of evaluation of this end point: The primary study end-point will be evaluated at the time of surgery after 28 days of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): we will compare the % change in the Ki67 level from baseline in the two treatment groups.; we will determine clinical efficacy (overall response rate, ORR) in terms of tumor size reduction (RECIST criteria) and in terms of pathologic complete responses at the time of surgical resection.; Further exploratory analysis for the identification of correlative biomarkers: we will calculate associations between the Ki67 results and the PAM50 proliferative signature. Moreover we will evaluate the association between Ki67 level and ATRA-21 to test the predictive power of the gene-expression model. Moreover we will determine the ATRA-21 signature, which predicts sensitivity of BC cell lines with great accuracy, and will be validated in the current clinical trial. ATRA-21 consists of 21 genes and the gene-expression signature can be determined from the RNA-sequencing data obtained in basal conditions. Correlations between ATRA-21 predictions and the response of patients to ATRA+anastrozole will be evaluated.; Patients will be monitored for adverse events (AEs) bi-weekly using the definitions and criteria for grading provided in the Common Terminology Criteria for adverse Events (CTCAE) 4.03.;Timepoint(s) of evaluation of this end point: The secondary study end-point will be evaluated at the time of surgery after 28 days of treatment.; The secondary study end-point will be evaluated at the time of surgery after 28 days of treatment.; The secondary study end-point will be evaluated at the time of surgery after 28 days of treatment.; 30 days after the last dose of study treatment. | — |
Countries
Italy
Contacts
Public ContactLaboratorio Metodologia per la Rice
IRCCS Istituto di Ricerche Farmacologiche Mario Negri
Outcome results
None listed