Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- Pathologic Response
研究概览
简要总结
This study will evaluate the safety and efficacy of eribulin in combination with carboplatin and trastuzumab in the neoadjuvant setting in subjects who are human epidermal growth factor receptor (HER)2 positive and are clinically stage IIA to IIIB.
The study regimen will be administered every 3 weeks for a total of 6 cycles followed by definitive surgery.
详细描述
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
eribulin: During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle.
carboplatin: Carboplatin area under the curve
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Written informed consent
- •Females; 18 years of age or greater
- •Histologically proven invasive breast cancer
- •American Joint Committee on Cancer (AJCC) clinical stage IIA - IIIB
- •Tumor size greater than 10 millimeters
- •HER2 positive
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Estrogen receptor (ER) positive or negative
- •Ejection fraction greater than or equal to lower limit of normal for the institution by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
- •Less than or equal to Grade 1 neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- •Planned lumpectomy or mastectomy
- •Eligible for radiation therapy
- •No prior treatment for invasive breast cancer
- •Adequate organ system function per protocol as determined within 7 days prior to first dose of study treatment
- •Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study treatment and must agree to use adequate contraception methods during study treatment and for a minimum of 6 months following trastuzumab discontinuation
- •Female subjects who are lactating should discontinue nursing prior to the first dose of study treatment and should refrain from nursing throughout the treatment period
排除标准
- •Fine needle cytology only without other histologic evidence of invasive breast cancer
- •Inflammatory breast cancer
- •AJCC clinical stage T1a-b breast cancer (primary tumor less than or equal to 10 millimeters)
- •Evidence of metastatic disease
- •HER2 negative
- •Ejection fraction less than lower limit of normal for the institution by ECHO or MUGA
- •Corrected QT interval greater than 480 milliseconds
- •Pre-existing cardiac dysfunction
- •Prior history of invasive cancer within the past 3 years
- •Synchronous bilateral breast cancer
- •Pre-existing CTCAE v4.0 Grade 2 or greater neuropathy
- •Hypersensitivity to halichondrin B or halichondrin B chemical derivative
- •History of severe allergic reactions to cisplatin or other platinum containing compounds, or mannitol
- •Mild, moderate, or severe hepatic impairment
- •Moderate or severe renal impairment
- •Hypokalemia or hypomagnesemia if it cannot be corrected prior to the first dose of study treatment
- •Organ allografts requiring immunosuppression
- •Known positive human immunodeficiency virus (HIV) status
- •Prior major surgery within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer
- •Minor surgery or radiation therapy within 14 days prior to the first dose of study treatment
- •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
研究组 & 干预措施
Eribulin, carboplatin, and trastuzumab
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
干预措施: eribulin (Drug)
Eribulin, carboplatin, and trastuzumab
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
干预措施: carboplatin (Drug)
Eribulin, carboplatin, and trastuzumab
During Phase I, the eribulin dose will be assigned upon study enrollment. The maximum tolerated dose (MTD) determined in Phase I will be the dose used for Phase II. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on Days 1 and 8 of each cycle. Carboplatin area under the curve (AUC) 6 will be administered IV over 15 to 30 minutes on Day 1 of each cycle. Trastuzumab will be administered as an IV infusion on Day 1 of each cycle. A loading dose of 8 mg/kg of trastuzumab will be administered over 90 minutes on Cycle 1 Day 1. Then, a maintenance dose of 6 mg/kg of trastuzumab will be administered over 30 to 90 minutes on Day 1 of Cycles 2 - 6.
干预措施: trastuzumab (Drug)
结局指标
主要结局
Pathologic Response
时间窗: Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start
Definitive surgery will be performed 3 to 8 weeks after completion of study treatment. The pathology report will be scored for pathologic response: complete pathologic response (no invasive cancer in breast or lymph nodes; residual DCIS or LCIS is acceptable), partial pathologic response (residual invasive cancer in breast and/or lymph nodes), or no response (pathologic staging is equal to or worse than pretreatment clinical staging).
次要结局
- Clinical Response(Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.)