A Phase 1b Study of Poziotinib in Combination With T-DM1 in Women With Advanced or Metastatic HER2-Positive Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a Phase 1b, open-label, multicenter study to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of poziotinib when administered with standard dosing of T-DM1 (3.6 mg/kg IV on Day 1 of each 21-day cycle) in women with advanced or metastatic HER2+ breast cancer. The poziotinib dose identified in Part 1 of the study will be used in combination with standard dose of T-DM1 in Part 2 of the study to confirm the poziotinib dose and evaluate the preliminary efficacy of the combination therapy.
详细描述
In Part 1, the dose of poziotinib, in combination with the standard dose of T-DM1 (3.6 mg/kg IV) on Day 1 of each cycle will be determined using a "3+3" design with up to 3 dose levels tested beginning with 8 mg/day.
Poziotinib dose escalation/de-escalation for the next dose cohort will proceed based on the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of the dose cohort. Patients in the dose cohort, if not discontinued, will continue treatment until discontinuation.
In Part 2 of the study, approximately 10 patients will be treated at the MTD/MAD to confirm dose for safety of the combination and to evaluate preliminary efficacy. Treatment for all patients will continue until disease progression, unacceptable toxicity, or continuation of study treatment is not in the best interest of the patient.
The Screening period (Day -30 to Day -1) will last up to 30 days prior to Cycle 1, Day 1.
During each 21-day cycle, eligible patients will receive poziotinib at the assigned dose, orally, once daily. T-DM1 3.6 mg/kg IV will be administered on Day 1 of each treatment cycle.
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 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patient must be female, at least 18 years of age, but not older than 90 years, with advanced or metastatic HER2+ breast cancer and a life expectancy of more than 6 months
- •Patient must have confirmed HER2 overexpression or gene-amplified tumor via immunohistochemistry [IHC] with IHC 3+ or IHC 2+ with confirmatory fluorescence in situ hybridization [FISH]+ or [ISH]+
- •Patients must have had at least 1 line of anti-HER2 directed therapy either in the metastatic or early-stage disease setting
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
排除标准
- •Patient has had previous treatment with poziotinib.
- •Patient has received anticancer chemotherapy, TKIs, biologics, immunotherapy, radiotherapy, or investigational treatment within 15 days. (There is no washout for hormonal therapy for breast cancer).
- •Patient has a life expectancy less than 3 years due to other malignancies.
- •Patient is pregnant or breast-feeding.
研究组 & 干预措施
Poziotinib
- Part 1: Dose Finding The MTD/MAD of poziotinib in combination with the standard dose of T-DM1 will be determined by using a "3+3" design. At least 3 patients may be enrolled in each cohort before a decision is made to proceed to the next cohort.
- Part 2: MTD/MAD Expansion An additional 10 patients will be treated at the dose identified during Part 1 to further evaluate the combination at the MTD or the MAD.
干预措施: T-DM1 (Drug)
Poziotinib
- Part 1: Dose Finding The MTD/MAD of poziotinib in combination with the standard dose of T-DM1 will be determined by using a "3+3" design. At least 3 patients may be enrolled in each cohort before a decision is made to proceed to the next cohort.
- Part 2: MTD/MAD Expansion An additional 10 patients will be treated at the dose identified during Part 1 to further evaluate the combination at the MTD or the MAD.
干预措施: Poziotinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 3 Years
Evaluate the Objective Response Rate (ORR) in patients treated with daily poziotinib in combination with T-DM1 (every 3 weeks) in women with advanced or metastatic HER2 positive breast cancer.
次要结局
- Disease Control Rate (DCR)(27 weeks)
- Progression-free Survival (PFS)(3 years)