Phase I and Phase I Trastuzumab Cohort Study of Entinostat, Lapatinib and Trastuzumab in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity
研究概览
简要总结
This phase I trial studies the side effects and best dose of entinostat when given together with lapatinib ditosylate and trastuzumab in treating patients with breast cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes or has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected. Entinostat and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. Giving entinostat together with lapatinib ditosylate and trastuzumab may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for entinostat in combination with lapatinib (lapatinib ditosylate) in patients whom trastuzumab has failed for human epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer (Phase I).
II. To determine the maximum tolerated dose (MTD) for entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
SECONDARY OBJECTIVES:
I. To determine the toxicity of combination therapy with entinostat and lapatinib in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I).
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients have histological confirmation of invasive breast carcinoma
- •Patients have locally recurrent or distant relapsed metastatic disease
- •Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
- •Patients are able to swallow and retain oral medication (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
- •Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Patients must have received prior trastuzumab for > 2 month period before disease recurrence or recurrence or progression while on trastuzumab-based therapy
- •Patients have ability and willingness to sign written informed consent
- •Female patients of childbearing potential (a female not free from menses > 2 years or not surgically sterilized) must be willing to use an adequate barrier method of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study; male patients who are able to father children must use an adequate barrier method of contraception
- •Female patients of childbearing potential must have negative serum pregnancy test within 14 days of starting protocol therapy
- •Patients with brain metastasis have no signs of progressive disease 4 months after the completion of brain metastasis treatment (radiation therapy, surgery, etc.) do not require anticonvulsants or corticosteroids, and have been off such drugs for at least 7 days
- •Both men and women and members of all races and ethnic groups are eligible for this trial
排除标准
- •Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, biological therapy and hormonal therapy) while taking study medication
- •Serum bilirubin >= 1.5 x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x ULN (with or without liver metastasis [mets])
- •Absolute neutrophil count (ANC) < 1.5
- •Hemoglobin =< 9
- •Platelet =< 140,000
- •Patients have an active infection and require intravenous (IV) or oral antibiotics
- •Cardiac arrhythmia requiring maintenance medication
- •History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- •Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety
- •Serum creatinine > 2.0 mg/dL
研究组 & 干预措施
Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
干预措施: Entinostat (Drug)
Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
干预措施: Lapatinib Ditosylate (Drug)
Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
干预措施: Trastuzumab (Biological)
结局指标
主要结局
RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity
时间窗: Up to 28 days
次要结局
- Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4(Up to 28 days)