A Pilot Study of Systemically Administered Bevacizumab in Patients With Neoplastic Meningitis (NM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Cerebrospinal Fluid (CSF) Response Rate: Percentage of Participants Positive for Tumor Cells
研究概览
简要总结
The goal of this clinical research study is to learn if and how Avastin (bevacizumab) may affect cancer that has spread to the meninges of the brain or the spinal cord. The safety of this drug will also be studied.
Objectives:
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Primary:
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Determine preliminary response data of intravenous bevacizumab in patients with NM
a. As measured by clearance of malignant cells from the Cerebrospinal fluid (CSF) at 2, 4, 6, 12, 18, and 24 weeks, then every 8 weeks up to 54 weeks, and
b. Time to neurological progression (TTNP)
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Secondary:
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Evaluate the safety of intravenous bevacizumab in patients with NM
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Further describe the efficacy of this intervention as measured by
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improvement of MR imaging evidence of disease
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overall survival
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maintenance of quality of life
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Determine effects of systemically administered bevacizumab on CSF, serum, and urine Vascular endothelial growth factor (VEGF)levels levels
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Correlate changes in CSF VEGF with response measurements.
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Correlate primary tumor tissue VEGF expression with CSF VEGF levels
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Correlate urine VEGF levels with serum and CSF VEGF levels
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Evaluate serum and CSF VEGF index
详细描述
The Study Drug:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
Study Drug Administration:
If you are found to be eligible to take part in this study, every 2 weeks, you will receive bevacizumab by vein over about 1 hour.
Study Visits:
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
- •History of breast cancer, lung cancer or melanoma
- •Diagnosis of NM as proven either by:
- •positive CSF cytology, or
- •magnetic resonance neuro-imaging, or
- •Age >/=18 years.
- •Routine laboratory studies adequate with bilirubin </= 1.5 x upper limit of normal (ULN), AST < 2.5 x ULN, creatinine <1.0 x ULN, granulocytes >1500, platelets> 75,000; Hb >/= 9.
- •Patient able to sign informed consent and willing to participate in study primary objectives
- •At least 1 week from last intrathecal chemotherapy (>2 weeks if liposomal cytarabine). Patients are allowed to have received prior chemotherapy for their tumor. No limit on prior chemotherapies will be made. Patients who have been treated with tyrosine kinase inhibitors are permitted. Prior anti-VEGF targeted therapy is not permitted, unless patient has been off anti-VEGF therapy for 6 months and did not develop NM while on anti-VEGF therapy
- •Karnofsky performance status (KPS) >/= 50%
- •Pre-treatment CSF Indium 111 CSF flow study without evidence of obstruction.
- •Patients on full-dose anticoagulants (e.g., warfarin) with PT international normalized ratio (INR) >1.5 are eligible provided that:
- •Patients are receiving anticoagulation (warfarin or low molecular weight heparins (LMWH)) only if the patients can be off of warfarin for 4-5 days prior to the LP and placed on LMWH in that interim, and if the 'treatment dose' of LMWH can be safely held for 24 hours before and after the LP.
- •continued) INR must be <1.2 prior to LP in this circumstance. If patients are receiving thromboprophylaxis dose of LMWH, the patients can be enrolled, but the thromboprophylaxis LMWH must be able to be safely held for 12 hours prior to the LP.
- •The patient has no active bleeding or pathological condition that carries a high risk of bleeding
- •There is no evidence of serious or non-healing wound, ulcer or bone fracture
- •Ventricular reservoir NOT mandatory
排除标准
- •Evidence of active CNS hemorrhage in the brain or tumor lesions
- •Besides NM, other known CNS disease, except for treated brain metastases(Patients must be at least 1 month out from brain irradiation and have no evidence of progression or hemorrhage at that time, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period). Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery or a combination as deemed appropriate by the treating physician.
- •continued) With respect to irradiation for other purpose (for NM or bone metastases, etc) patients need only 1 week out from the completion of irradiation. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- •Patients with clinically significant cardiovascular disease are excluded 1) Inadequately controlled HTN (SBP > 140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg despite antihypertensive medication). 2) Prior history of hypertensive crisis or hypertensive encephalopathy. 3) New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- •Continued) 4) History of myocardial infarction or unstable angina within 6 months prior to Day
- •History of stroke or transient ischemic attack within 6 months prior to Day
- •Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day
- •Clinically significant peripheral vascular disease. 8) Serious and inadequately controlled cardiac arrhythmia
- •History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day
- •Ventricular reservoir must have been placed more than 28 days prior to Day
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- •Serious, non-healing wound, active ulcer, or untreated bone fracture
- •Proteinuria as demonstrated by UPC ratio >/=1.0 at screening or by urine dipstick >/= 2+. (Patients discovered to have >/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
- •Known hypersensitivity to any component of bevacizumab
- •Intrathoracic or extrathoracic lung carcinoma of squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is acceptable.
- •continued) Patients with extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral lung lesions (of any non squamous NSCLC histology, except small cell histology) will also be eligible (a peripheral lesion is defined as a lesion in which the epicenter of the tumor is </= 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is >/= 2 cm from the trachea, main, and lobar bronchi).
- •Pregnant (positive pregnancy test) or nursing women. Angiogenesis is critical to fetal development and the inhibition of angiogenesis following administration of AVASTIN is likely to result in adverse effects on pregnancy. There are no adequate and well-controlled studies in pregnant women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 2 months after the completion of bevacizumab therapy.
- •General Medical Exclusions 1) Inability to comply with study and/or follow-up procedures 2) Life expectancy of less than 6 weeks 3) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this Genentech supported study 4) Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years
研究组 & 干预措施
Bevacizumab
Bevacizumab 10 mg/kg by vein over about 1 hour, every 2 weeks.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Cerebrospinal Fluid (CSF) Response Rate: Percentage of Participants Positive for Tumor Cells
时间窗: 1 year (54 weeks) of treatment
CSF response for participants with Neoplastic Meningitis (NM) or leptomeningeal disease (LMD) defined as conversion from positive to negative cytology or cytometry as measured routinely by total clearance of malignant cells from the CSF where assessments performed from 2 weeks up to week 54 of treatment. Clearance of malignant cells determined by standard clinical testing using cytospin analysis in clinical laboratory. Percentage reflects number of participants of total treated with no response, e.g. participants with continued positive CSF cytology or flow cytometry.
Median Time to Progression (TTP) and Median Time to Neurological Progression (TTNP)
时间窗: 6 weeks
Time to Progression defined as time to disease progression measured from date of enrollment, confirmation of disease progression via laboratory testing; Time to neurological progression (TTNP) reflects worsening clinical signs/symptoms or development of new clinical signs/symptoms which investigator feels can be attributed to leptomeningeal disease progression and are severe enough to warrant a change in therapy.
次要结局
未报告次要终点