Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT03822468
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of the study was to evaluate the safety and efficacy of a reduced ribociclib starting dose of 400 mg in combination with a non-steroidal aromatase inhibitor (NSAI) (letrozole or anastrozole) for the treatment of pre- and postmenopausal women with hormone receptor-positive (HR-positive), HER2-negative advanced breast cancer (aBC) who have received no prior therapy for advanced disease. Premenopausal women were required to receive goserelin in both treatment arms.
- Detailed Description
Patients were assigned at visit Cycle 1 Day 1 to one of the following two treatment arms in a ratio of 1:1:
* Experimental arm: Ribociclib 400 mg (2 × 200 mg tablets by mouth) QD on Days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (Days 22 to 28) in combination with ET consisting of:
• For postmenopausal women:
* Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously
• For premenopausal women:
* Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks.
* Control arm: Ribociclib 600 mg (3 × 200 mg tablets by mouth) QD on Days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (Days 22 to 28) in combination with ET consisting of:
* For postmenopausal women:
\~ Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously.
* For premenopausal women:
* Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks.
Participants received study treatment until disease progression (radiologically documented according to RECIST 1.1 criteria), unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.
For participants who discontinued treatment for reasons other than documented disease progression, death, lost to follow-up, or withdrawal of consent, tumor assessments continued to be performed until disease progression, death, lost to follow-up, or withdrawal of consent (post-treatment efficacy follow-up).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 376
Not provided
- 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). Patients in whom ≥
- 25% of the bone marrow has been previously irradiated are also excluded.
- 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.
Other protocol-defined Inclusion/Exclusion may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ribociclib 400 mg Ribociclib Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women) Ribociclib 400 mg Anastrozole Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women) Ribociclib 400 mg Letrozole Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women) Ribociclib 400 mg Goserelin Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women) Ribociclib 600 mg Ribociclib Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women) Ribociclib 600 mg Anastrozole Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women) Ribociclib 600 mg Letrozole Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women) Ribociclib 600 mg Goserelin Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to 23.8 months ORR defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by local investigators according to RECIST 1.1.
CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
- Secondary Outcome Measures
Name Time Method Change From Baseline in QTc (With Fridericia's Correction) at Cycle 1 Day 15 (at 2 Hours Post-dose) Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days Electrocardiogram (ECG) data was collected via 12-lead digital ECG machines. Change from baseline in the QT interval (a segment of the ECG that reflects the time it takes for the heart to repolarize after each heartbeat) was corrected for heart rate using Fridericia's formula (ΔQTcF).
Progression-free Survival (PFS) Up to approximately 60 months Progression free survival (PFS) was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. PFS was censored if no PFS event was observed. The censoring date was the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression. PFS was assessed via a local radiology assessment as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1.
Clinical Benefit Rate (CBR) Up to approximately 60 months Clinical benefit rate (CBR) was defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR), or an overall response of stable disease (SD), lasting for at least 24 weeks. CR, PR, and SD were defined as per local review as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1. A patient was considered to have SD for 24 weeks or longer if a SD response was recorded at 24-1=23 weeks or later from randomization, allowing for the ±1 week visit window for tumor assessments.
CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.Time to Response (TTR) Up to approximately 60 months Time to response (TTR) was defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which had to be subsequently confirmed (although the date of initial response was used, not the date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1.
CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.Duration of Response (DOR) Up to approximately 60 months Duration of response (DOR) only applied to patients whose best overall response was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progression or death due to underlying cancer. Patients continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.
CR: Disappearance of all lesions with lymph nodes measuring \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.Pharmacokinetics (PK) of Ribociclib: Maximum Observed Plasma Concentration (Cmax) Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days PK parameters were calculated by non-compartmental analysis. Cmax is the maximum observed plasma drug concentration after single dose administration.
PK of Ribociclib: Time to Reach Observed Maximum Concentration (Tmax) Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days PK parameters were calculated by non-compartmental analysis. Tmax is the time to reach maximum observed plasma concentration. Actual recorded sampling times were considered for the calculations.
PK of Ribociclib: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days PK parameters were calculated by non-compartmental analysis. AUC0-24 is the area under the plasma concentration-time curve from 0 to 24 hours
Trial Locations
- Locations (15)
Southern Cancer Center PC
🇺🇸Mobile, Alabama, United States
Rocky Mountain Cancer Centers
🇺🇸Longmont, Colorado, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Comprehensive Cancer Cntr Of Nevada
🇺🇸Henderson, Nevada, United States
New York Oncology Hematology
🇺🇸Albany, New York, United States
Mount Sinai School Of Medicine
🇺🇸New York, New York, United States
Millennium Research Clin Develop
🇺🇸Houston, Texas, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Marin Cancer Care
🇺🇸Greenbrae, California, United States
Florida Retina Institute
🇺🇸Orlando, Florida, United States
Scroll for more (5 remaining)Southern Cancer Center PC🇺🇸Mobile, Alabama, United States