“Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer”
QT interval prolongation and neutropenia are considered to be important identified risks for ribociclib (KisqaliAR Prescribing Information, Investigator Brochure). The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1 week off schedule. The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without compromising the efficacy of ribociclib in combination with an NSAI in pre- and postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy for advanced disease. The risks of other AEs of special interest, such as neutropenia and hepatobiliary toxicity will be evaluated in this study as well. Approximately 350 patients will be randomly assigned to one of the below treatment arms in a 1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization will be stratified by the presence of lung and/or liver metastases (yes versus no).
Drug - Ribociclib
Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
Drug - Letrozole or Anastrozole
Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)
Drug - Goserelin
Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)
A Phase II, Multicenter, Randomized, Open-label Study to Evaluate the Safety and Efficacy of 400 mg of Ribociclib in Combination With Non-steroidal Aromatase Inhibitors for the Treatment of Pre- and Postmenopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease