A Three-arm, Randomized, Open Label, Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in the Treatment of Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 309
- 试验地点
- 20
- 主要终点
- Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone
研究概览
简要总结
This was a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.
详细描述
The reference therapy (control arm) used in the course of this trial was the combination arm of everolimus plus exemestane. The investigational therapies in the context of this study were everolimus monotherapy and capecitabine monotherapy. All treatments were taken orally until disease progression, intolerable toxicity or withdrawal of patient's informed consent. Patients were randomly assigned with equal allocation to one of the treatment arms:
- Exemestane (25mg daily) in combination with everolimus (10mg daily)
- Everolimus (10mg daily)
- Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.
Treatment assignment was stratified by the presence of visceral disease (yes vs. no). Visceral refered to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites.
Randomization and Treatment Phase:
At Visit 3 all eligible patients were randomized in 1:1:1 ratio to receive everolimus (10mg daily oral tablets) in combination with exemestane (25 mg daily oral tablets), everolimus (10mg daily oral tablets) or capecitabine monotherapy (1250mg/m2 twice daily orally for two weeks followed by a one week rest period in 3-weeks cycles). Assignment was stratified by the presence of visceral disease (yes vs. no). Visceral refered to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites. After randomization, study treatment started and continued until progression, intolerable toxicity or consent withdrawal. Further treatment after progression and study treatment discontinuation was at the investigator's discretion. Dose adjustment (reduction, interruption) according to safety findings was allowed. Regular safety and efficacy reviews by Data Monitoring Committee (DMC) were performed. Tumor assessments were performed every 6 weeks until disease progression. Additional evaluation were performed to confirm response at 4 weeks after it was first observed. After at least 150 PFS events had been documented per RECIST 1.1 by local assessment in each of the two following groups: (i) everolimus + exemestane arm plus everolimus monotherapy arm, and (ii) everolimus + exemestane arm plus capecitabine monotherapy arm, the frequency of tumor assessments was changed to every 12 weeks or as clinically indicated.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion ≥ 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness ≤ 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.
排除标准
- •Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.
研究组 & 干预措施
Capecitabine 1250 mg/m2
Capecitabine (1250 mg/m2 twice daily) for two weeks, followed by one week rest period in 3-weeks cycles (investigational arm).
干预措施: Capecitabine (Drug)
Everolimus 10 mg
Everolimus (10 mg daily) (investigational arm).
干预措施: Everolimus (Drug)
Everolimus 10 mg + Exemestane 25 mg
Everolimus (10 mg daily) with Exemestane (25 mg daily) (control arm).
干预措施: Exemestane (Drug)
Everolimus 10 mg + Exemestane 25 mg
Everolimus (10 mg daily) with Exemestane (25 mg daily) (control arm).
干预措施: Everolimus (Drug)
结局指标
主要结局
Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone
时间窗: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy.
次要结局
- Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone(Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months)
- Clinical Benefit Rate (CBR)(From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months)
- Overall Survival (OS)(Every 3 months following end of treatment visit, assessed for approximately 54 months)
- Overall Response Rate (ORR)(From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months)
- Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration(Baseline, every 6 weeks up to about 43 months)
- Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life(Baseline, every 6 weeks up to about 43 months)
- Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12(Week 3, Week 12)