Targeting Aurora A Kinase to Overcome Treatment Resistance in Advanced HR+/HER2+ Breast Cancer: A Biomarker-Driven Pilot Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clinical benefit defined as partial tumor response (PR)
研究概览
简要总结
The goal of this clinical trial is to learn if alisertib in addition to usual care works to treat HR+/HER2+ breast cancer. The main questions it aims to answer are:
- Does alisertib stop the communication between HR and HER2?
- Are there genetic markers that predict how well someone's cancer will respond to alisertib?
Participants will receive alisertib in addition to their usual care.
详细描述
This pilot clinical trial will evaluate alisertib in combination with standard of care endocrine therapy and Human Epidermal Growth Factor Receptor-2 (HER2)-targeted therapy in participants with Stage IV hormone receptor positive (HR+)/ HER2 positive (HER2+) breast cancer, utilizing our novel 3-gene biomarker signature for patient selection and response prediction
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
- •* Age \> 18 years at the time of consent.
- •* ECOG performance status \/=60%).
- •* Metastatic HR+/HER2+ breast cancer (estrogen receptor (ER) and/or progesterone receptor (PR) ≥1%, HER2 3+ by immunohistochemistry (IHC) or amplified by in situ hybridization (ISH).
- •* Prior standard induction treatment with chemotherapy + trastuzumab + pertuzumab (HP) or fam-trastuzumab deruxtecan (T-DXd) and have completed a minimum of 4 cycles without progressive disease.
- •* Planned to start or are receiving endocrine therapy + HER2-directed (HP or pertuzumab/trastuzumab/hyaluronidase-zzxf (PHESGO®)) therapy.
- •* Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.
- •* Left ventricular ejection fraction ≥ 50% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) documented within 6 weeks prior to the study treatment.
- •* Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors volume 1.1 (RECIST 1.1) or evaluable disease with circulating tumor DNA (ctDNA) that is detectible. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
- •* Willingness to receive growth factor injections for neutropenia prophylaxis. Only patients without any grade 3 or higher neutropenia during induction chemotherapy or T-DXd will be permitted to proceed without prophylactic growth factor support. If the enrolled patients in this trial develop high grade or prolonged neutropenia, the addition of growth factor will be required.
排除标准
- •Active infection requiring systemic therapy.
- •Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
- •Treatment with any investigational drug within 14 days prior to registration, or within 5 half-lives of the investigational product, whichever is longer.
结局指标
主要结局
Clinical benefit defined as partial tumor response (PR)
时间窗: 12 weeks
As defined by RECIST 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Clinical benefit defined as complete tumor response (CR)
时间窗: 12 weeks
As defined by RECIST 1.1 Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
Clinical benefit defined as decline in circulating tumor DNA (ctDNA)
时间窗: 12 weeks
Clinical benefit is defined as a decline in ctDNA by \>50%.
次要结局
- Evaluate safety of adding alisertib to usual care by assessing adverse events(12 weeks)
- BRD8 signature expression(12 weeks)