Comparative Effects of Ribociclib and Palbociclib on Circulating and Tumor Infiltrating Myeloid Cells in Metastatic Breast Cancer Patients
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Immune cell frequency (relative abundance, cells per parental cell)
研究概览
简要总结
This clinical trial attempts to understand the differences between two chemotherapy drugs, ribociclib and palbociclib, and how they fight cancer. This study looks at tissue and blood characteristics of patients receiving these therapies in the hopes to develop a way to predict which medication would provide the most benefit to an individual patient.
详细描述
PRIMARY OBJECTIVE:
I. To identify predictive immune biomarkers and mechanisms of response to ribociclib or palbociclib in advanced, hormone receptor positive breast cancer patients.
SECONDARY OBJECTIVES:
I. Identify changes in antigen presentation machinery and costimulatory molecules on circulating myeloid cells as a result of ribociclib or palbociclib treatment.
II. Characterize the dynamic remodeling of circulating myeloid cell composition that occur as a result of ribociclib or palbociclib treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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 with histological confirmed breast adenocarcinoma who meet the following criteria:
- •Age: >= 18 years and are post-menopausal
- •Estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 (HER2) negative breast cancer patients who prospectively may undergo evaluation for Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), ribociclib or palbociclib, as part of first-line therapy. Retrospective cohorts will be built to include either ribociclib or palbociclib treated patients with known clinical outcome
- •During routine standard of care procedure, tumor that is accessible for ultrasound guided biopsy (from breast, lymph node, subcutaneous tumor, or selected liver metastasis per treating physician's discretion) or skin punch biopsy (for dermal metastasis) will be collected
- •Available tumor tissue or planning on biopsy prior to initiation of CDK4/6i treatment
- •Available tumor tissue or planning on biopsy at time of progression, prior to initiating subsequent therapy
- •Willing to provide consent for extra tissue and blood samples
排除标准
- •Patient received prior treatment with any CDK4/6 inhibitor
- •Prior treatment with any chemotherapy for metastatic disease
- •Patient is cognitively impaired
- •Lung or bone metastasis only (not accessible by ultrasound guided biopsy)
- •Patients with central nervous system (CNS) involvement unless they meet ALL the following criteria:
- •Untreated brain metastases (e.g., lesions < 1cm) not needing immediate local therapy
- •Previously treated brain metastases not needing immediate local therapy
- •At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
- •Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
- •Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
- •Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
- •That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
- •Herbal preparations/medications, dietary supplements
- •Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is allowed
- •Patient is currently receiving or has received systemic corticosteroids =< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment
- •The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
结局指标
主要结局
Immune cell frequency (relative abundance, cells per parental cell)
时间窗: From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years
Will be assessed by high dimensional flow cytometry. One-way analysis of variance (ANOVAs) and non-parametric Kruskal-Wallis tests will be used to compare relative abundances across patient groups and over the course of therapy. Wilcoxon rank-sum test will be used to examine the association between each biomarker of each sample collection and pathological response as appropriate. Odds ratios and 95% conference intervals will be calculated to measure strength of associations. P-values \< 0.05 will be considered statistically significant. No adjustment for multiple comparisons will be used in view of the exploratory nature of this analysis.
次要结局
- Cells per mm^2 tissue(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Average cell-cell distances (within neighborhood)(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Single-cell gene expression(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Psuedotime gene trajectory(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Number of spatial clusters(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Cells per mm^2 cancer island(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Number of core cells with cell(s) in neighborhood(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)
- Cells per mm^2 stroma(From date of initiation of CDK4/6 inhibitor (either ribociclib or palbociclib) to disease progression (clinical or imaging), or, up to a maximum of 5 years)