Patients with primary operable stage II, grade 2 or 3, Ki67 =20%, HR+/HER2- breast cancer to evaluate safety and long-term efficacy of a non-chemo treatment in patients biologically responders to neoadjuvant ribociclib and letrozole.
Conditions
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Signed Informed Consent Form prior to any study-specific procedure. 2- Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent).3- Male (=18 years old) or pre-menopausal women (=40 years old) or post-menopausal women. Premenopausal/male patients will receive LHRH agonists 2 weeks before C1D1 and during treatment. 4- Histologically confirmed invasive breast carcinoma, confirmed by the local pathologist. 5-Breast cancer eligible for primary surgery. 6-Available pre-treatment FFPE core (tru-cut) biopsy evaluable for PAM50 or possibility to obtain one. 7-Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 8- Adequate hematological, renal and hepatic function. 9-A male participant must agree to use a contraception as detailed in Appendix 1 of this protocol during the adjuvant chemotherapy period (only non-responder cohort) and for at least 21 days, corresponding to time needed to eliminate any study treatments plus an additional 120 days (a spermatogenesis cycle) after the last dose of chemotherapy and refrain from donating sperm during this period. 10-A female participant is eligible to participate if she is not pregnant, not breastfeeding. 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 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 230
Exclusion criteria
Exclusion criteria: 1. Any prior treatment for primary invasive breast cancer. Letrozole or other drugs used during the preservation of ovarian function are permitted if administered after baseline biopsy. 2. Inoperable breast cancer. 3. Patients with Stage I, III or IV breast cancer are not eligible. 4. Bilateral invasive breast cancer. 5. Patients who have undergone sentinel lymph node biopsy prior to study treatment. 6. Inability or unwillingness to swallow pills. 7. Malabsorption syndrome or other condition that would interfere with enteric absorption of study drugs. 8. Participation in a prior investigational study within 30 days prior to enrolment or within 5 half-lives of the investigational product, whichever is longer. 9. Patient with a Child-Pugh score B or C. 10. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: a. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening. b. History of documented congestive heart failure (New York Heart Association functional classification III-IV). c. Documented cardiomyopathy. d. Patient has a Left Ventricular Ejection Fraction (LVEF) 500 msec or conduction abnormality in the previous 12 months. i. On screening 12-lead ECG, any of the following cardiac parameters: bradycardia (resting heart rate 90), PR interval >220 msec, QRS interval >109 msec, or QTcF interval =450 msec (using Fridericia’s correction). j. Uncontrolled hypertension (Systolic blood pressure >160 mmHg or 100 mmHg). 11. Active infection requiring intravenous (IV) antibiotics. 12. Prior story of pneumonitis of any cause. 13. Prior thromboembolic events not attributable to a clear trigger cause. 14. Known human immunodeficiency virus (HIV) infection. 15. 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. 16. Significant traumatic injury within 3 weeks prior to initiation of study treatment. 17. Major surgical procedure (not including minor procedures such as lymph node biopsy, tumor core biopsy, fine needle aspiration or bilateral oophorectomy) within 3 weeks prior to initiation of study treatment or not fully recovered from any side effects of previous procedures. 18. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 19. Patients with a history of any malignancy are ineligible except for the following circumstances: • Patients with a malignancy history other
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term efficacy of neo/adjuvant endocrine therapy + ribociclib in high-risk ER+/HER2-disease and a biological response at surgery (i.e., ROR-low);Secondary Objective: 1. To evaluate the long-term efficacy of neo/adjuvant endocrine therapy + ribociclib in high-risk ER+/HER2- disease and a biological response at surgery (i.e., ROR-low). 2. To evaluate the efficacy of ribociclib and endocrine therapy during neoadjuvant treatment. 3. To evaluate the long-term efficacy of neo/adjuvant endocrine therapy + ribociclib in high-risk ER+/HER2- disease and a lack of biological response at surgery (i.e., ROR-med/high). 4. To evaluate the safety and tolerability of investigational treatment and their corresponding standard treatment;Primary end point(s): Distant metastasis-free survival (DMFS) DMFS is defined as the time from date of surgery to date of first event of distant metastatic recurrence or death (any cause).;Timepoint(s) of evaluation of this end point: The time from date of surgery to date of first event of distant metastatic recurrence or death (any cause). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.1 Invasive disease-free survival (IDFS): iDFS is defined as the time from surgery until the date of the first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive disease, a distant disease recurrence, contralateral invasive breast cancer, second primary or death from any cause. 2.1 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. 2.2 Rate of RCB0/1 after neoadjuvant treatment, according to the MD Anderson Cancer Center procedures, as per local assessment. 3.1 Estimation of DMFS in ROR-med/high group. 4.1. Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 4.03, including dose reductions, delays and treatment discontinuations.;Timepoint(s) of evaluation of this end point: 1) The time from surgery until the date of the first occurrence of invasive disease (defined at the protocol) 2) At the time of definitive surgery 3) The time from date of surgery to date of first event of distant metastatic recurrence or death (any cause). 4) From the signature of the IC until the 30-day post-ribociclib safety visit (approximately after 3 years from patient inclusion) | — |
Countries
France, Spain
Contacts
Public ContactClinical project Manager
UNICANCER
Outcome results
None listed