HR-positive, HER2-negative advanced breast cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864 MedDRA version: 23.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 1007
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy. -Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgRpositive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory. -Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample. -Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation). -Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. -Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory: QTc interval at screening =65 years) yes F.1.3.1 Number of subjects for this age range 87
Exclusion criteria
Exclusion criteria: -Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator’s judgment. -Patient who received any prior systemic anti-cancer therapy (including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible. -Patient is concurrently using other anti-cancer therapy. -Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities. -Patient has received extended-field radiotherapy = 4 weeks or limited field radiotherapy = 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion). -Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ. -Patients with central nervous system (CNS) involvement unless they meet specific stability criteria. -Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. -Patient is currently receiving or has received systemic corticosteroids = 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment. Please refer to Section 5.2 of the protocol for details on exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine whether the overall response rate (ORR) in the experimental arm (400 mg) is non-inferior to the control arm (600 mg) based on local tumor assessments (RECIST version1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.;Secondary Objective: Key secondary objective is to evaluate QTc (with Fridericia's correction) prolongation in the experimental arm. Other secondary objectives include safety and tolerability, progression-free survival, clinical benefit rate, time to response, duration of response, pharmacokinetics of ribociclib when given in combination with NSAI. ;Primary end point(s): Overall response rate (ORR). ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.;Timepoint(s) of evaluation of this end point: After all patients have been treated for 6 months or have discontinued study treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -? QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint) -Progression-free survival (PFS) -Clinical benefit rate (CBR) -Time to response (TTR) -Duration of response (DOR) -Pharmacokinetics (PK) of ribociclib: Cmax -Pharmacokinetics (PK) of ribociclib: Tmax -Pharmacokinetics (PK) of ribociclib: AUC0 - 24h ;Timepoint(s) of evaluation of this end point: After all patients have been treated for 6 months or have discontinued study treatment. | — |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Costa Rica, Czechia, Czech Republic, Finland, France, Germany, Hungary, India, Jordan, Lithuania, Peru, Portugal, Russian Federation, South Africa, Sweden, Thailand, United States
Contacts
Public ContactMedical information
Novartis Sverige AB
Outcome results
None listed