HER2 NEGATIVE/LUMINAL BREAST CANCER MedDRA version: 20.0 Level: LLT Classification code 10006283 Term: Breast neoplasm malignant female System Organ Class: 100000004864
Conditions
Interventions
Trade Name: FEMARA - 30 COMPRESSE 2.5 MG
Product Name: letrozolo
Product Code: [letrozolo]
Pharmaceutical Form: Tablet
INN or Proposed INN: LETROZOLO
CAS Number: 112809-51-5
Current Sponsor code: Letr
Sponsors
FONDAZIONE DEL PIEMONTE PER L'ONCOLOGIA IRCCS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to provide written informed consent 2. Over 18 years of age 3. Histological diagnosis of invasive breast cancer 4. Radiological evidence (mammography and / or ultrasound) strongly suggestive for the presence of invasive mammary neoplasia (BIRADS 4c or BIRADS 5) with a diameter greater than 15mm 5. Stage I carcinoma (if diameter> 15 mm) or II, operable d'emblée, or 6. Stage II or III cancer, operable following neoaduvant hormonal therapy in patients not eligible for neoadjuvant chemotherapy, 7. Onset stage IV carcinoma, asymptomatic, with operable emblée primary breast cancer or following presurgical therapy, not candidates for combination of letrozole with biological agents (eg. CDK 4/6 inhibitors) 8. Tumor of luminal immunophenotype A or B, according to ESMO guidelines (Luminal A: ER positive, Ki67 20%; Luminal B; ER positive and Ki67=20% or PgR 5% 11. Postmenopausal state to. Postmenopausal status is defined by the presence of at least one of the following criteria: the. age = 60 years ii. age between 45-59 years as long as one or more of the following criteria are met: 1. amenorrhea = 12 months in the presence of the uterus in place; 2. amenorrhea for less than 12 months and FSH within the postmenopausal range, including patients who have undergone hysterectomy, or in chemotherapy-induced amenorrhea; 3. bilateral adnexectomy at age> 18 years. 12. Ability to take oral therapy, in the absence of known malabsorption syndrome, previous stomach or small bowel surgery 13. Ability to perform the staging and screening exams required by the protocol 14. ECOG Performance status = 0 15. Patients should have normal bone marrow, liver and kidney function as defined by the following biochemical values: to. Leukocytes = 3,000 / ¿L. b. Absolute count of neutrophils = 1,500 / ¿L c. Platelets = 100,000 / ¿L d. Total bilirubin within normal reference values is. AST (SGOT) / ALT (SGPT) = 2.5X upper limit of normal f. Creatinine within normal reference values ¿¿or creatinine clearance = 60mL / min / 1.73m² for patients with creatinine levels above normal 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 177 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 59
Exclusion criteria
Exclusion criteria: 1. Previous treatment for breast cancer with chemotherapy, lapatinib, trastuzumab, letrozole, anastrozole, exemestane or tamoxifen. 2. Indication for neoadjuvant chemotherapy 3. Metastatic disease for which an association of letrozole with biological agents is indicated (eg CDK 4/5 inhibitors) 4. Other malignancies diagnosed within the past 5 years, except basal cell or squamous skin carcinoma, melanoma in situ or cervical cancer in situ. 5. Premenopause 6. Known hypersensitivity to letrozole, or to any of its excipients (for example: women with rare hereditary problems of galactose intolerance, lactase deficiency or glucose / galactose malabsorption). 7. Evidence of severe and poorly controlled systemic disease affecting the lung, heart, liver, kidney that may compromise adherence to treatment or prolonged follow-up. 8. Uncontrolled chronic inflammatory bowel disease (example: Crohn's disease, ulcerative colitis). 9. Active and / or inadequately controlled infections. 10. Altered mental status, senile dementia, or any psychiatric condition that may impair the ability to knowingly sign informed consent. 11. Triple negative breast cancer, i.e. negative for both the overexpression of HER2 and the expression of hormone receptors.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to confirm the role of miR-100 expression as metabolic response marker of patient treated with anti-hormone drugs;Secondary Objective: Define and validate a genomic signature based on miR-100 expression to predict Luminal A subtipe. Gene expression profiling;Primary end point(s): Proportion of patients with complete proliferative response (ki67 value =2.7%) after short treatment in relation to the basal expression of miR-100 dichotomized around the value of =4.343.;Timepoint(s) of evaluation of this end point: A Ki67 value =2.7 detected after a short treatment with hormonal therapy (21 +/- 3 days) defines the proliferative response to treatment (“complete cell cycle arrest” CCCA). The response will be assessed by measuring the reduction in Ki67 following hormonal treatment according to a schedule defined on the basis of the stage of the disease: • Patients with operable emblée tumor: at the time of surgery (about 3 weeks) • Candidate patients for neoadjuvant hormone therapy and patients with stage IV onset of hormone therapy for advanced disease: During the 3rd week from the start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison of the proliferative response measured as a percentage reduction of Ki67 from baseline, after short treatment, based on miR-100 levels. • Correlation between the response to hormonal treatment (both complete proliferative response and percentage reduction in Ki67 compared to baseline values) and the expression of miR-100 target genes (mTOR, FOXA1, PLK1, FGFR3 and IGF1R). • Evaluation of sensitivity and specificity of the gene signature developed in the BC-P1-2013 study in identifying Luminal A tumors defined by PAM50 gene expression tests.;Timepoint(s) of evaluation of this end point: • Patients with operable emblée tumor: at the time of surgery (about 3 weeks) • Candidate patients for neoadjuvant hormone therapy and patients with stage IV onset of hormone therapy for advanced disease: During the 3rd week from the start of treatment | — |
Countries
Italy
Contacts
Public ContactClinical Research Office
Istituto di Candiolo
Outcome results
None listed