Patients with advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer
Conditions
Interventions
Trade Name: KISQALI 200 MG
Product Name: Ribociclib
Product Code: LEE011
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ribociclib
CAS Number: -
Current Sponsor code: LEE011
Other descri
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male/female patients =18 years of age 2. HR-positive and HER2-negative breast cancer by local testing 3. ECOG performance status of 0 to 1. 4. Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer. 5. Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period. 6. HER2-E or Basal-like subtype as per central PAM50 analysis. 7. Measurable disease or non-measurable (but evaluable), as defined by RECIST v1.1. 8. Adequate hematologic and end-organ function 9. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. 10. Women of childbearing potential must have confirmed negative serum pregnancy test. 11. Women of CBP must be willing to use highly effective methods of contraception. 12. Postmenopausal OR Pre/perimenopausal status as defined in protocol 13. Patients must have the ability to swallow oral medication. 14. Patient must have a 6-lead or 12-lead ECG at screening 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 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Prior therapy with any CDK4/6 inhibitors. 2. Patient has received prior treatment with chemotherapy for advanced / metastatic breast cancer (neoadjuvant/ adjuvant chemotherapy for early breast cancer is allowed). 3. Patient has received extended-field radiotherapy = 4 weeks or limited field radiotherapy = 2 weeks prior to enrollment and has not recovered to grade 1 or better from related side effects of such therapy. Patients in whom = 25% of the bone marrow has been previously irradiated are also excluded[60]. 4. Any ongoing acute toxic effects of prior anti-cancer therapy or major surgical procedures to NCI CTCAE version 4.03 Grade = 1 at day of inclusion. 5. Uncontrolled pleural effusion, pericardial effusion, or ascites. 6. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 7. Known active central nervous system metastases and/or carcinomatous meningitis. 8. Known history of Human Immunodeficiency Virus (HIV). 9. Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 10. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality 11. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol or limit life expectancy to =6 months. 12. Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) 13. Pregnant or breast-feeding women or women who plan to become pregnant or breast-feed during the trial. 14. Not able to understand and to comply with study instructions and requirements according to investigator criteria. For HER2-E cohort only: 15. Patient with a known hypersensitivity to any of the excipients of ribociclib, palbociclib and/or endocrine therapy 16. Patient is currently receiving any protocol-prohibited substances within 7 days before randomization 17. Patient is currently receiving or has received systemic corticosteroids = 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment. 18. Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments For Basal-like cohort only: 19. History of hypersensitivity reactions to paclitaxel or other drugs formulated in the same solvent as paclitaxel (polyoxyethylated castor oil)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare PFS of ribociclib plus endocrine therapy over palbociclib plus endocrine therapy with respect to PFS in patients with advanced hormone receptor-positive, HER2-negative and HER2-E breast cancer.;Primary end point(s): Progression-free survival using RECIST 1.1 criteria, as assessed by local radiologists/investigators;Timepoint(s) of evaluation of this end point: Image testing will be done mandatory, every 8 weeks (+/- 7 days) for the first 12 months, then every 12 weeks (+/- 7 days);Secondary Objective: •To compare the two treatment arms with respect to Progression on next-line therapy (PFS2) in the HER2-E cohort •To compare the two treatment arms with respect to overall survival in the HER2-E cohort •To evaluate the two treatment arms with respect to overall response rate (ORR) and clinical benefit rate (CBR) in the HER2-E cohort. •To describe time to response and duration of response in each treatment arm in the HER2-E cohort. •To evaluate the safety and tolerability of ribociclib and palbociclib in combination with endocrine therapy in the HER2-E cohort •To evaluate patient reported outcomes for health-related quality of life in the two treatment arms of the HER2-E cohort. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS2, defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first OS Overall response and clinical benefit as defined by RECIST 1.1. Time to response and duration of response per RECIST 1.1 Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions Time to 10% deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 Change from baseline in the global health status/QOL scale score of the EORTC QLQ-C30 Change from baseline in the fatigue scale score of the FACT-G score of FACIT Fatigue Scale (Version 4);Timepoint(s) of evaluation of this end point: 1.Follow up for PFS2 and OS will be every 6 months 2.Image testing will be done mandatory, every 8 weeks (+/- 7 days) for the first 12 months, then every 12 weeks (+/- 7 days) 3.Safety (incidence of AEs) will be monitored continuously, until 30 days after discontinuation 4.Patient reported outcomes will be done every two cycles for the first 12 months, then every three cycles | — |
Countries
Portugal, Spain, United States
Contacts
Public ContactAREA DE INVESTIGACION CLINICA
SOLTI
Outcome results
None listed