A Phase 2 Study of Alisertib in Combination With Endocrine Therapy in Patients With HR+, HER2-negative Recurrent or Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 225
- 试验地点
- 102
- 主要终点
- Objective Response Rate (ORR) Within Dose Subgroup
研究概览
简要总结
PUMA-ALI-1201 is a randomized, dose optimization, multicenter, Phase 2 study of alisertib administered in combination with endocrine therapy in participants with pathology-confirmed HR-positive/HER2-negative metastatic breast cancer (MBC) following progression on or after at least two prior lines of endocrine therapy in the recurrent or metastatic setting. This study is intended to evaluate the optimal alisertib dose administered in combination with the selected endocrine therapy. The study is also planned to evaluate the efficacy, safety, and pharmacokinetics of alisertib in combination with endocrine and to identify the biomarker-defined subgroup(s) that may benefit most from combined alisertib and endocrine therapy. Participants randomized prior to Amendment 4 are randomized 1:1:1 to Arm 1, Arm 2 or Arm 3. Participants randomized under Amendment 4 will be randomized 1:1 to Arm 1 or Arm 2.
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
- 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
- •Aged ≥18 years at signing of informed consent.
- •Pathology-confirmed diagnosis of breast cancer with evidence of recurrent or metastatic disease not amenable to curative therapy.
- •Progression on or after treatment with at least two prior lines of endocrine therapy in the recurrent or metastatic setting. a. If metastatic disease recurrence occurs during or within six months of discontinuing adjuvant endocrine therapy, then that endocrine therapy will count as one line of prior therapy.
- •Participants must have received a CDK4/6i in combination with endocrine therapy in the recurrent or metastatic setting.
- •HR-positive and HER2-negative tumor status reported per local laboratory testing. HR and HER2 testing must be performed consistent with current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society of Medical Oncology (ESMO) guidelines.
排除标准
- •Treatment with chemotherapy in the recurrent or metastatic setting, including antibody drug conjugates with a chemotherapeutic payload.
- •Prior treatment with an Aurora Kinase A (AURKA) specific-targeted or pan-Aurora-targeted agent, including alisertib, in any setting.
- •Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
结局指标
主要结局
Objective Response Rate (ORR) Within Dose Subgroup
时间窗: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.
Duration of Response (DOR) Within Dose Subgroup
时间窗: From start date of response (after date of randomization) to first PD, assessed up to 48 months
Duration of response is measured from the time at which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.
Disease Control Rate (DCR) Within Dose Subgroup
时间窗: From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months
Disease control rate is the proportion of participants who achieve overall tumor response (confirmed CR or PR) or Stable Disease (SD) lasting for at least 24 weeks from randomization.
Progression Free Survival (PFS) Within Dose Subgroup
时间窗: From date of randomization to date of recurrence, progression or death, assessed up to 48 months
Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of randomization until the first date on which recurrence, progression, or death due to any cause, is documented.
Overall Survival (OS) Within Dose Subgroup
时间窗: From date of randomization to death, assessed up to 48 months
Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.
Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) in the Enrolled Population
时间窗: From date of first dose through last dose plus 28 days, assessed up to 48 months
Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after last dose.
Adverse events (AEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0)
Adverse events (AEs) and serious adverse events (SAEs) per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0)
Objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS)
Objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS)
次要结局
- Objective Response Rate (ORR) Within Biomarker-Defined Subgroup(From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months)
- Duration of Response (DOR) Within Biomarker-Defined Subgroup(From start date of response (after date of randomization) to first PD, assessed up to 48 months)
- Disease Control Rate (DCR) Within Biomarker-Defined Subgroup(From date of randomization to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 48 months)
- Progression Free Survival (PFS) Within Biomarker-Defined Subgroup(From date of randomization to date of recurrence, progression or death, assessed up to 48 months)
- Overall Survival (OS) Within Biomarker-Defined Subgroup(From date of randomization to death, assessed up to 48 months)
- ORR, DOR, DCR, PFS, and OS within biomarker-defined subgroups from retrospectively evaluated patient samples
- Plasma alisertib concentrations collected on C1D1, C1D3, C1D8, and C1D18.
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