A Phase II Evaluating Cabazitaxel in Patients With Brain Metastasis Secondary to Breast and Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Reduction of brain lesions.
研究概览
简要总结
A phase II trial evaluating Cabazitaxel in patients with brain metastasis secondary to breast and non-small-cell lung cancer (NSCLC).
OBJECTIVES:
Primary:
The purpose of this study is to determine if cabazitaxel can induce a reduction in the size brain metastasis in metastatic HER2-negative breast cancer and NSCLC with brain metastasis who were not previously treated with whole brain irradiation or require immediate brain irradiation.
Secondary:
- To determine the effect of cabazitaxel on the time to initiating whole brain irradiation or radiosurgery
- To determine the effect of cabazitaxel on the time to developing neurological symptoms
- To determine the effect of cabazitaxel on the time to disease progression in the brain
- To determine the effect of cabazitaxel on the time to disease progression outside the brain. This will be evaluated separately for the breast and NSCLC cohorts To determine the objective extra-cranial response (if applicable). This will be evaluated separately in the breast and NSCLC cohorts
- To determine the safety of cabazitaxel
详细描述
This is a single arm, prospective trial using a 2-stage Simon design, in which eligible patients will receive intravenous cabazitaxel for two cycles followed by response evaluation. Based on the pre-specified criteria of response (intra-cranial, patient will be allowed to continue on study drug.
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
- •Signed informed consent
- •Age>18, ECOG 0-1
- •Histologically confirmed 1) HER2-negative invasive breast carcinoma or 2) NSCLC
- •In patients with breast cancer, HER2-negative status by FISH or immunohistochemistry (score 0, or +1).
- •In patients with breast cancer, known estrogen and progesterone receptor status.
- •Evidence of measurable disease in the brain (at least 1cm)
- •Stable or decreasing dosage of steroids for 7 days prior to baseline MRI.
- •No evidence of (cortical) cognitive impairment as defined by a Mini-Mental Status Exam (MMSE) score ≥ 25/
- •No more than 4 prior lines of systemic chemotherapy in the metastatic setting
- •Adequate hematopoietic function defined as:
- •Hemoglobin ≥ 9.0g/dL
- •Absolute neutrophilic count ≥ 1.5 x 109L
- •Platelet count ≥ 100 x 109L
- •Adequate hepatic function defined as:
- •AST ≤ 2.5 x upper limit of normal (ULN)
- •ALT ≤ 2.5 x ULN
- •Total bilirubin ≤ 1.0 x ULN
- •Adequate renal function defined as serum creatinine ≤ 1.5 x ULN. If creatinine ranges from 1.0 - 1.5 x ULN, creatinine clearance determined by CKD-EPI formula should be calculated and only patients with clearance >60 mL/min are eligible
- •Adequate contraceptive method in patients with child-bearing potential.
排除标准
- •History of prior whole brain irradiation
- •Progressive neurological symptoms requiring immediate brain irradiation
- •Pregnancy or lactation
- •History of hypersensitivity reaction to taxanes
- •History of hypersensitivity to polysorbate 80 containing agents
- •Current or planned treatment with strong inhibitors or inducers of cytochrome P
- •Less than 3 weeks since the last treatment of chemotherapy, biological therapy, and/or immunotherapy
- •Leptomeningeal carcinomatosis
- •Contra-indication to contrast-enhanced MRI
研究组 & 干预措施
Cabazitaxel
Eligible patients will receive intravenous 25mg/m2 cabazitaxel every 3 weeks. Contrast-enhanced whole brain MRI will be performed every two cycles. Patients who show ≥50% volumetric reduction in the size of the brain lesion(s) will continue on cabazitaxel until disease progression or unacceptable toxicity. Patients who show evidence of disease progression and/or developed progressive neurological symptoms will be taken off study and offered whole brain irradiation. Patients who do not meet both criteria can have the choice either to continue on study drug or to be taken off study according to the investigator discretion.
干预措施: Cabazitaxel (Drug)
Cabazitaxel
Eligible patients will receive intravenous 25mg/m2 cabazitaxel every 3 weeks. Contrast-enhanced whole brain MRI will be performed every two cycles. Patients who show ≥50% volumetric reduction in the size of the brain lesion(s) will continue on cabazitaxel until disease progression or unacceptable toxicity. Patients who show evidence of disease progression and/or developed progressive neurological symptoms will be taken off study and offered whole brain irradiation. Patients who do not meet both criteria can have the choice either to continue on study drug or to be taken off study according to the investigator discretion.
干预措施: Contrast-enhanced whole brain MRI (Procedure)
结局指标
主要结局
Reduction of brain lesions.
时间窗: week 6
Objective response defined as a \>= 50% volumetric reduction of brain lesions in the absence of increasing steroid use and progressive neurologic symptoms.
次要结局
- Time to developing neurological symptoms.(every 6 weeks until disease progression.)
- Toxicity(every 3 weeks until 30 days after last treatment administration.)
- Time to progression extra-cranial(every 6 weeks until disease progression.)
- Time to whole brain irradiation or radiosurgery(every 6 weeks until disease progression.)
- Time to progression in the brain(every 6 weeks until disease progression.)