Luminal B/HER2-negative breast cancer.
Conditions
Interventions
Trade Name: FEMARA
Product Name: Letrozole
Pharmaceutical Form: Coated tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form prior to any study-specific procedure. 2. Female patients. 3. Post-menopausal status and age =18 years. Post-menopausal status is defined as: ? Age = 60 years or ? Age =65 years) yes F.1.3.1 Number of subjects for this age range 94
Exclusion criteria
Exclusion criteria: 1. Any prior treatment for primary invasive breast cancer. 2. Inoperable locally advanced or inflammatory (i.e., inoperable Stage III) breast cancer. 3. Metastatic (Stage IV) breast cancer. 4. Bilateral invasive breast cancer. 5. Multicentric breast cancer, defined as the presence of two or more foci of cancer in different quadrants of the same breast. 6. Patients who have undergone sentinel lymph node biopsy prior to study treatment. 7. Inability or unwillingness to swallow pills. 8. Malabsorption syndrome or other condition that would interfere with enteric absorption of study drugs. 9. Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer. 10. Patient with a Child-Pugh score B or C. 11. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: ? History of acute coronary syndromes or symptomatic pericarditis within 12 months prior to screening. ? History of documented congestive heart failure (NYHA functional classification III-IV). ? Documented cardiomyopathy. ? Patient has a Left Ventricular Ejection Fraction (LVEF) 500 msec or conduction abnormality in the previous 12 months. ? On screening 12-lead ECG, any of the following cardiac parameters (defined as the mean of triplicate ECGs: bradycardia (resting heart rate 90), PR interval > 220 msec, QRS interval >109 msec, or QTcF interval =450 msec (using Fridericia’s correction). 12. Uncontrolled hypertension (Systolic blood pressure >160 mmHg or 100 mmHg). 13. Active infection requiring intravenous (IV) antibiotics. 14. Symptomatic hypercalcemia despite adequate management. 15. Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis. 16. Known human immunodeficiency virus (HIV) infection. 17. Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may compromise compliance with the protocol, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications. 18. Significant traumatic injury within 3 weeks prior to initiation of study treatment. 19. Major surgical procedure (not including minor procedures su
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the clinical benefit of ribociclib plus letrozole versus chemotherapy.; Secondary Objective: 1. To compare additional measures of clinical benefit of ribociclib plus letrozole versus chemotherapy. 2. To compare the rate of breast conserving surgery (BCS) and transition to BCS of investigational treatment arms versus their corresponding standard treatment arm. 3. To compare the anti-proliferative effect of treatment arms as per molecular indicators. 4. To assess the effect of investigational treatment versus standard treatment on patient reported outcomes (PROs). 5. To evaluate the safety and tolerability of investigational treatment versus their corresponding standard treatment. 6. To identify biomarkers of response or resistance to the study treatments. ;Primary end point(s): Rate of residual cancer burden (RCB) score 0 or 1 (RCB0/1) after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per central assessment.;Timepoint(s) of evaluation of this end point: After surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.1 Tumor overall objective response rate (ORR), defined as the sum of Partial Responses (PR) and Complete Responses (CR) according to RECIST v1.1, as per Investigator’s assessments by breast MRI. 1.2 ORR by physical examination, mammography and breast US, if available. 1.3 pCR in the breast (pCRB) defined as the complete absence of invasive carcinoma in the breast on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast. 1.4 pCR in the breast and axillary lymph nodes (pCRBL) after completion of study treatment, defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination at the time of definitive surgery, irrespective of in situ carcinoma in the breast. 1.5 Rate of residual cancer burden (RCB) score 0 or 1 (RCB0/1) after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment. 1.6 Preoperative endocrine prognostic index (PEPI) score in the ribociclib plus letrozole treatment arm compared to historical values. 2.1 Rate of breast conserving surgery (BCS): patients to whom a BCS was recommended from the beginning plus patients who were supposed to undergo a mastectomy but after neoadjuvant therapy became suitable for a BCS approach versus patients who underwent a mastectomy. 3.1 Decrease in Ki67 from baseline to week 2, from baseline to surgery, from week 2 to surgery and from baseline to progression (in those patients who consent for early termination biopsy). To be assessed in both treatment arms. 3.2 Rates of Luminal A disease (at surgery) in patients with residual disease in the breast at surgery. 3.3 Change to Luminal A or ROR-low disease from baseline to week 2, from baseline to surgery, from week 2 to surgery and from baseline to progressi | — |
Countries
Spain
Contacts
Public ContactGestion de Proyectos
SOLTI
Outcome results
None listed