Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer
Pilot Phase II Study of Metronomic Chemotherapy in Combination With Avastin in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
研究概览
详细说明
This is a non-randomized, open-label, pilot Phase II study of metronomic chemotherapy plus Avastin in chemo naïve subjects with advanced non-squamous, non-small cell carcinoma of the lung. The primary endpoint of this study is to assess the overall progression-free survival.
Subjects will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks, and Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated every 8 weeks.
Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will then continue until disease progression, intolerable toxicity or withdrawal of consent.
Potential biologic parameters to monitor anti-tumor activity of metronomic chemotherapy will be evaluated in 10 subjects. These biomarkers include: sequential determination of blood levels of VEGF, VEGFR2, thrombospondin-1, E-selectin, ICAM-1, and circulating endothelial cells and endothelial precursor cells.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Alabama
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Birmingham、Alabama、美国、35294 - 0104
- University of Alabama at Birmingham
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Neutrophil Count greater than or equal to 1500/μL
- Platelet Count greater than or equal to 100,000/μL
- Hemoglobin greater than or equal to 9.0g/dL
- Total Bilirubin ≤ 1.5mg/dL
- Transaminases ≤ 2.5 x ULN
- Serum Creatinine ≤ 1.5 x ULN
- Proteinuria: Urine protein: creatinine (UPC) ratio < 1.0 at screening OR Urine dipstick for proteinuria < 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
INR ≤ 1.5 and a PTT no greater than the ULN
- Subjects must be 19 years or older.
- Subjects with a history of hypertension must be well-controlled (< 150/100) on a stable regimen of anti-hypertensive therapy.
- Subjects must not have serious non-healing wound ulcer, or bone fracture, or major surgical procedure within 28 days prior to starting treatment.
- Subjects must not have radiation therapy within 3 weeks prior to initiation of treatment.
- Female subjects must be postmenopausal, surgically sterile, or using effective contraception. All females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the initiation of treatment.
- Informed consent must be obtained in writing prior to the initiation of treatment.
Exclusion Criteria
- Inability to comply with study and/or follow-up procedures
- Life expectancy of less than 12 weeks
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
- Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
Avastin-Specific Exclusions
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Known CNS disease, except for treated brain metastasis Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, 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 (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- History of hemoptysis (greater than or equal to 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 1
- 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 a UPC ratio greater than or equal to 1.0 at screening
- Known hypersensitivity Criteria:
- Pathological-proven NSCLC except squamous cell carcinoma as the predominant histology.
- Advanced NSCLC: Stage IIIB with pleural effusion or Stage IV or recurrent disease.
- Measurable or non-measurable disease as defined by solid tumor response criteria (RECIST)
- ECOG Performance Status 0 to 1.
- No prior systemic chemotherapy or biologic therapy.
- Required laboratories (obtained ≤ 1 week prior to the initiation of treatment)
- Absolutely any component of Avastin
- Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in patients of child-bearing potential
- Intrathoracic 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. Patients with extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral lung lesions (of any NSCLC histology) will also be eligible (a peripheral lesion is defined as a lesion in which the epicenter of the tumor is less than or equal to 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is greater than 2 cm from the trachea, main, and lobar bronchi).
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Paclitaxel and Gemcitabine + Avastin
Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks).
Avastin will be administered every 2 weeks.
Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent.
Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.
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Paclitaxel Dose Levels:
其他名称:
Premedication
Gemcitabine Dose Levels:
其他名称:
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Progression-Free Survival (PFS)
大体时间:Baseline to 24 months
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Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences disease progression in accordance with the Response Evaluation Criteria Solid Tumors (RECIST v1.0).
The RECIST criteria indicates progression as a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.
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Baseline to 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Number of Participants With Adverse Events
大体时间:Baseline through duration of treatment an average of 1 year
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All adverse events will be recorded as to the grade and relationship to the study drug in accordance with the Common Terminology Criteria for Adverse Events (CTCAE v 3.0)
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Baseline through duration of treatment an average of 1 year
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Overall Survival (OS)
大体时间:Baseline up to 84 months
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Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences death or lost to follow up.
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Baseline up to 84 months
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Objective Response Rate
大体时间:Baseline up to 12 months
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The percentage of patients who achieve a complete response and partial response according to RECIST criteria (v1.0).
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Baseline up to 12 months
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合作者和调查者
合作者
调查人员
- 首席研究员:Francisco Robert, M.D.、University of Alabama at Birmingham
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- F070727010
- UAB 0709
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
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Paclitaxel的临床试验
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Fujian Cancer HospitalJiangsu Hengrui Pharmaceutical Co., Ltd.; SunWay Biotech Co., LTD.尚未招聘肝转移 | 恶性黑色素瘤