Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).
研究概览
简要总结
This is a phase II clinical trial to assess the efficacy of the combination of metronomic cyclophosphamide and tailored sorafenib dosing in advanced, progressive NET. NET are highly vascular tumors, and high VEGF expression has been correlated with worse clinical and pathological characteristics as well as poor prognosis. A novel antiangiogenic approach relies on targeting not only the endothelial cells but also rendering them more sensitive to VEGFR blockade by achieving pericyte detachment. In this study, the dose of sorafenib will be titrated up to a maximum of 800mg BID based on patients' toxicity and on a novel pharmacodynamic assay that measures inhibition of molecular target(PDGFR) in patients' peripheral blood mononuclear cells. Dual VEGFR targeting is achieved by administering sorafenib plus metronomic low dose cyclophosphamide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 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
- •Histologically or cytologically confirmed neuroendocrine tumors
- •Progressive and measurable metastatic disease
- •Patients must not have disease that is currently amenable to surgery
- •Life expectancy of greater than 3 months
- •ECOG performance status ≤2
- •Patients must have normal organ and marrow function
- •Negative pregnancy test; agreement to use adequate birth control
排除标准
- •Patients receiving chemotherapy or radiotherapy within last 4 weeks
- •Patients that had received Sorafenib for advanced NET(neuroendocrine tumors) are not allowed
- •Any other investigational agents within 4 weeks of study
- •Patients with known brain metastases
- •History of allergic reactions to compounds of similar chemical/biologic composition to sorafenib or cyclophosphamide
- •Concurrent cancer from another primary site requiring treatment within the past 3 years
- •Uncontrolled intercurrent illness
- •Pregnant women and women who are breastfeeding
- •HIV-positive patients receiving combination anti-retroviral therapy
研究组 & 干预措施
I
Patients will receive sorafenib and cyclophosphamide.
干预措施: Sorafenib (Drug)
I
Patients will receive sorafenib and cyclophosphamide.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).
时间窗: Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
Objective response (complete and partial) evaluated using RECIST criteria. Complete response (CR): disappearance of all clinical and radiological evidence of tumour (both target and non-target). Partial response (PR): at least a 30% decrease in the sum of longest diameter of target lesions.
Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib
时间窗: Assessed from start of study treatment until death, assessed up to 7 years.
A phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells was used in order to predict clinical course and/or guide individual dose-titration. Positive pShift values denote stimulation of RAF signal transduction, whereas negative pShift values denote inhibition of RAF signal transduction as measured by flow-cytometry. Associations between pShift changes and treatment efficacy were measured using progression-free survival (PFS) and overall survival (OS).
次要结局
- Progression-free Survival (PFS)(Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years)
- 1-year Survival Rate(1 year)
- Overall Survival (OS)(Assessed from start of study treatment until death, assessed up to 7 years.)