A Randomized, Double-blind, Placebo Controlled, Phase II Study of Everolimus in Combination With Exemestane in the Treatment of Chinese Postmenopausal Women With Estrogen Receptor Positive, HER-2 Negative, 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
- 159
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
研究概览
简要总结
This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole.
详细描述
This was a multicenter, double-blind, randomized, placebo-controlled, phase II study evaluating treatment with everolimus (10 mg daily) in combination with exemestane (25 mg daily) vs placebo in combination with exemestane (25 mg daily) in Chinese postmenopausal women with locally advanced, recurrent or metastatic ER+ HER2- breast cancer refractory to non-steroidal aromatase inhibitors.
Randomized participants started the study treatment at Cycle 1 Day 1, and were treated continuously until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reason.
After end of treatment, all participants were followed up for safety up to 30 days after last dose of study treatment (exemestane and/or everolimus/placebo). All participants were followed for survival status at least every 3 months after treatment discontinuation unless they discontinued due to death, consent withdrawal or lost to follow-up
If a participants permanently discontinued study treatment for reasons other than disease progression, death, lost to follow-up, or withdrawal of consent to efficacy follow-up then they entered the post-treatment efficacy follow-up period until disease progression, death, lost to follow-up or withdrawal of consent for efficacy follow-up.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Chinese Postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy.
- •Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
- •Postmenopausal women. Postmenopausal status was defined either by:
- •Prior bilateral oophorectomy
- •Or age ≥60
- •Or age < 60 and amenorrhea for 12 or more months
- •Recurrence or progression on prior NSAI was defined as:
- •Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole
- •Or Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole
- •Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment
- •Patient had as per RECIST 1.1
- •measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
- •non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
- •Patient was able to swallow and retain oral medication
- •Patient met the hematologic and biochemistery laboratory values at the screening visit
- •Patient had a WHO performance status ≤2
- •Written informed consent obtained prior to any screening procedures
排除标准
- •HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test.
- •Patients who had received more than one chemotherapy line for ABC
- •Patients with symptomatic visceral disease and candidates to chemotherapy
- •Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.)
- •Patients receiving concomitant immunosuppressive agents or chronic corticosteroids used at the time of study entry except topical applications, inhaled sprays, eye drops or local injections.
- •Uncontrolled diabetes mellitus as defined by HbA1c >7% despite adequate therapy.
研究组 & 干预措施
Placebo + Exemestane
Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg
干预措施: Everolimus Placebo (Drug)
Everolimus + Exemestane
Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg
干预措施: Everolimus (Drug)
Everolimus + Exemestane
Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg
干预措施: Exemestane (Drug)
Placebo + Exemestane
Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg
干预措施: Exemestane (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
时间窗: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
次要结局
- Overall Survival (OS)(From randomization to date of death, up to approximately 3.8 years)
- Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment(Up to approximately 3.5 years)
- Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment(Up to approximately 3.5 years)
- Time to Response (TTR) Based on BIRC Assessment(Up to approximately 1.8 years)
- Exemestane Predose Concentration (Cmin)(Predose of exemestane on Cycle 1 Week 4 ( each cycle is defined as 4 weeks))
- Overall Response Rate (ORR) Based on BIRC Assessment(Up to approximately 1.8 years)
- Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment(Up to approximately 3.5 years)
- Clinical Benefit Rate (CBR) Based on BIRC Assessment(Up to approximately 1.8 years)
- Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment(From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years)
- Duration of Response (DOR) Based on BIRC Assessment(From date of first documented response to date of first documented disease progression or death, assessed up to approximately 1.8 years)
- Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline(From randomization up to definitive deterioration of the ECOG PS by one categotu of the score, assessed up to approximately 3.5 years)
- Everolimus Concentration at 2 Hours Post Dose (C2h)(Two hours post everolimus administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks))
- Estradiol Levels After 4 Weeks of Study Treatment(Baseline, and at Cycle 1 Week 4 prior to any study drug (each cycle is defined as 4 weeks))
- Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment(From date of first documented response to date of first documented disease progression or death, assessed up to approximately 3.5 years)
- Everolimus Predose Concentration (Cmin)(Predose on Cycle 1 Week 4 ( each cycle is defined as 4 weeks))
- Exemestane Concentration at 2 Hours Post Dose (C2h)(Two hours post exemestane administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks))