A Randomized, Double-Blind, Phase II Trial of Fulvestrant Plus Enzastaurin Versus Fulvestrant Plus Placebo in Aromatase Inhibitor-Resistant Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Achieved a Best Response of Complete Response, Partial Response, and Stable Disease (CR+PR+SD) (Clinical Benefit Rate)
研究概览
简要总结
The primary purpose of this study is to help answer the following research question: whether enzastaurin given together with fulvestrant can help participants who have breast cancer and make the tumor smaller or disappear and for how long.
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
- •Female participants with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be estrogen response (ER) and/or parathyroid hormone receptor (PtR) positive.
- •Note: Hormone receptor positivity is defined as ER or PtR greater than 10 fmol/mg by biochemical assay or 10% positive cells by immunohistochemistry
- •Participants are resistant to aromatase inhibitors (AI) therapy
- •Females with postmenopausal status
- •Previous radiation therapy is allowed, but should have been limited
- •Measurable or non-measurable disease
- •Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have adequate organ function
- •Have an estimated life expectancy of at least 24 weeks
- •Must sign an informed consent document
排除标准
- •Have had prior treatment with fulvestrant or enzastaurin
- •Are receiving concurrent administration of any other antitumor therapy, with the exception of gonadotropin-releasing hormone (GnRH) antagonists.
- •Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry
- •Have received supplemental estrogen or progesterone within 4 weeks prior to study entry
- •Are hormone estrogen receptor (HER2)-positive
- •Are unable to discontinue use of anticoagulants
- •Have hypercalcemia
- •Have a second primary malignancy that is clinically detectable at the time of consideration for study enrollment
- •Have documented central nervous system (CNS) metastases, symptomatic pulmonary lymphangitis, or involvement of more than 1/3 of the liver
- •Have a serious concomitant systemic disorder
- •Have a serious cardiac condition
- •Are unwilling or unable to discontinue use of carbamazepine, phenobarbital, or phenytoin at least 14 days prior to study therapy
- •Are unable to swallow tablets.
研究组 & 干预措施
Enzastaurin + Fulvestrant
Participants received Enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 500 mg orally (QD) once daily in a 28-day cycle.
Participants received enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 250 mg orally (BID) twice daily in a 28-day cycle.
Fulvestrant was given intramuscularly at a loading dose of 500 mg on Day 1 and 250 mg on Day 15 in Cycle 1. Subsequent doses of Fulvestrant 250 mg were given on Day 1 of Cycle 2 and every 28 days thereafter.
干预措施: enzastaurin (Drug)
Enzastaurin + Fulvestrant
Participants received Enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 500 mg orally (QD) once daily in a 28-day cycle.
Participants received enzastaurin loading dose of 1125 mg, on Day 1 of Cycle 1 only then received Enzastaurin 250 mg orally (BID) twice daily in a 28-day cycle.
Fulvestrant was given intramuscularly at a loading dose of 500 mg on Day 1 and 250 mg on Day 15 in Cycle 1. Subsequent doses of Fulvestrant 250 mg were given on Day 1 of Cycle 2 and every 28 days thereafter.
干预措施: fulvestrant (Drug)
Fulvestrant + Placebo
Participants received fulvestrant: 500 mg, IM, day 1, 1250 mg, IM, day 15 cycle 1 then 250 mg, IM, every 28 days, until disease progression. Then, participants received placebo, oral, daily.
干预措施: placebo (Drug)
Fulvestrant + Placebo
Participants received fulvestrant: 500 mg, IM, day 1, 1250 mg, IM, day 15 cycle 1 then 250 mg, IM, every 28 days, until disease progression. Then, participants received placebo, oral, daily.
干预措施: fulvestrant (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved a Best Response of Complete Response, Partial Response, and Stable Disease (CR+PR+SD) (Clinical Benefit Rate)
时间窗: Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks)
Clinical benefit rate is defined as the rate of confirmed CR, confirmed PR, and SD for 24 weeks duration and is the best response CR, PR, or SD as classified by the investigators according to the RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Kaplan-Meier (KM) techniques were used to assess the time-to-event endpoints. Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir.
次要结局
- Number of Participants Who Discontinued With Adverse Events (AE) and Serious Adverse Events (SAEs)(From Baseline to Study Completion (Up to 3 years, 9 months))
- Percentage of Participants With Enzastaurin Biomarkers and Disease State(Baseline, Cycle 2 to Study Completion (Up to 3 Years, 9 Months))
- Progression Free Survival (PFS)(Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 3 Years))
- Duration of Clinical Benefit(Time of Clinical Benefit to Progressive Disease or Death (Up to 3 Years))
- Percentage of Participants Achieving Overall Tumor Response Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR])(Baseline to Measured Progressive Disease or Study Discontinuation (Up to 24 Weeks))