eMonarcHER: A Randomized, Double Blind, Placebo-Controlled Phase 3 Study of Abemaciclib Plus Standard Adjuvant Endocrine Therapy in Participants With High-Risk, Node-Positive, HR+, HER2+ Early Breast Cancer Who Have Completed Adjuvant HER2-Targeted Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 111
- 试验地点
- 114
- 主要终点
- Invasive Disease Free Survival (IDFS)
研究概览
简要总结
The main purpose of this study is to measure how well abemaciclib works in participants with early breast cancer who are taking hormone therapy after surgery. Participants must have breast cancer that is hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+). Your participation could last up to 10 years depending on how you and your tumor respond.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have confirmed HR+, HER2+ early invasive breast cancer without evidence of disease recurrence or distant metastases
- •Have undergone definitive surgery of the primary breast tumor(s)
- •Have tumor tissue from breast (preferred) or lymph node
- •Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or adjuvant setting per standard of care
- •Have completed approximately nine to 20 months of standard HER2-targeted therapy (neoadjuvant/adjuvant combined duration)
- •Have received one of the following eligible HER2-targeted adjuvant regimens AND be randomized within 12 weeks of completing the regimen:
- •For participants treated with neoadjuvant therapy and HER2-targeted therapy: A minimum of 4 cycles of T-DM1 in the adjuvant setting. NOTE: Participants may have received up to approximately 6 cycles of adjuvant trastuzumab prior to initiation of T-DM
- •Additionally, participants may have switched to trastuzumab-based therapy (monotherapy or in combination with other HER2-targeted therapies) after 4 cycles of T-DM1
- •For participants who had definitive surgery prior to systemic therapy, a minimum of 4 cycles of adjuvant pertuzumab with trastuzumab.
- •Have high risk disease, defined by one of the following criteria:
- •Those who received neoadjuvant chemotherapy along with HER2-targeted treatment must have:
- •residual disease in at least one axillary lymph node, or
- •a residual tumor ≥ 5 cm, or
- •a residual tumor of any size that has direct extension to the chest wall and/or skin (ulceration or skin nodules).
- •Those who had definitive surgery prior to systemic therapy and completed adjuvant chemotherapy along with HER2-targeted therapies (trastuzumab and pertuzumab) must have
- •tumor involvement in ≥4 ipsilateral axillary lymph nodes, or
- •tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and histological Grade 3, or
- •primary invasive tumor size of ≥ 5 cm on pathological evaluation.
排除标准
- •Have breast cancer with any of the following features:
- •Disease recurrence or distant metastatic disease (including contralateral axillary lymph nodes)
- •Pathological complete response from any prior early breast cancer treatments. Participants are required to have residual primary tumor and/or lymph node disease at the time of definitive surgery as indicated in inclusion criteria.
- •Inflammatory breast cancer
- •Have other medical conditions including:
- •Previous breast cancer (Exceptions: Ipsilateral ductal carcinoma in situ [DCIS] treated by locoregional therapy alone ≥5 years ago; contralateral DCIS treated by locoregional therapy at any time)
- •Other cancer being treated and/or not in complete remission within the last 5 years (Exceptions: Appropriately treated non-melanomatous skin cancer or carcinoma in situ of cervix, bladder, or colon)
- •Females who are pregnant or lactating
- •History of venous thromboembolism
- •Other serious medical conditions
- •Have previously received treatment with:
- •Any cyclin-dependent kinase (CDK)4 and CDK6 inhibitor
- •Prior adjuvant treatment with immunotherapy, tucatinib, neratinib, any investigational HER2 directed therapy, or T-DXd (DS8201) for treatment of breast cancer
- •Endocrine therapy (ET) (i.e., tamoxifen, raloxifene or aromatase inhibitor) for breast cancer prevention (without diagnosis of breast cancer)
- •Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard of care at study enrollment
研究组 & 干预措施
150 mg Abemaciclib + Endocrine Therapy (ET)
Participants received 150 milligrams (mg) of abemaciclib administered twice daily (BID) orally along with standard adjuvant endocrine therapy (ET).
干预措施: Abemaciclib (Drug)
150 mg Abemaciclib + Endocrine Therapy (ET)
Participants received 150 milligrams (mg) of abemaciclib administered twice daily (BID) orally along with standard adjuvant endocrine therapy (ET).
干预措施: Standard Adjuvant ET (Drug)
Placebo + ET
Participants received placebo administered BID orally along with standard adjuvant ET.
干预措施: Standard Adjuvant ET (Drug)
Placebo + ET
Participants received placebo administered BID orally along with standard adjuvant ET.
干预措施: Placebo (Drug)
结局指标
主要结局
Invasive Disease Free Survival (IDFS)
时间窗: Randomization to Recurrence or Death from Any Cause (up to 890 days)
IDFS, as defined by the STEEP System, is measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause. Study was terminated early. Data was not collected for this outcome and outcome measures were not assessed.
次要结局
- Overall Survival (OS)(Randomization to Death from Any Cause (up to 890 days))
- Distant Relapse-Free Survival (DRFS)(Randomization to Distant Recurrence or Death from Any Cause (up to 890 days))
- Percentage of Participants With Central Nervous System (CNS) Metastases as First Site of Disease Recurrence(Randomization to Distant Recurrence or Death from Any Cause (up to 890 days))
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score(Cycle 1 up to 390 days)
- Change From Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index Score(Cycle 1 up to 390 days)
- Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib(Day 1 of Cycles 1-3 (Cycle = 28 days))