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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 376
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •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.
研究组 & 干预措施
Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
干预措施: Ribociclib (Drug)
Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
干预措施: Anastrozole (Drug)
Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
干预措施: Letrozole (Drug)
Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
干预措施: Goserelin (Drug)
Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
干预措施: Ribociclib (Drug)
Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
干预措施: Anastrozole (Drug)
Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
干预措施: Letrozole (Drug)
Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
干预措施: Goserelin (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 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.
次要结局
- 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)
- Progression-free Survival (PFS)(Up to approximately 60 months)
- Clinical Benefit Rate (CBR)(Up to approximately 60 months)
- Time to Response (TTR)(Up to approximately 60 months)
- Duration of Response (DOR)(Up to approximately 60 months)
- 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 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 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)