Phase II Trial Of Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Overall Objective Response
研究概览
简要总结
The purpose of this study is to test whether an experimental drug called bevacizumab given together with gemcitabine and docetaxel, a standard chemotherapy regimen for sarcoma, can help sarcoma patients. This trial will examine what effects, good and/or bad the combination of gemcitabine, docetaxel and bevacizumab has on sarcoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed unresectable metastatic or locally recurrent leiomyosarcoma, Malignant Fibrous Histiocytoma (MFH, also known as high grade Undifferentiated Pleomorphic Sarcoma) pleomorphic liposarcoma, rhabdomyosarcoma or angiosarcoma.
- •Zero to one prior chemotherapy regimens for metastatic disease. Prior adjuvant therapy will not count provided it was more than one year previously.
- •Measurable disease as defined by RECIST
- •Adequate performance status - ECOG 0 or 1
- •Patients must be recovered from the toxic effects of prior chemotherapy or radiation. Therapy may not start until at least 3 weeks since prior cytotoxic chemotherapy, two weeks from completion of radiation therapy, and one week for patients on tyrosine kinase inhibitors or other targeted therapy.
- •Age 18 To
- •As it is quite difficult to administer high dose docetaxel with gemcitabine, to the elderly, in order to protect patient safety, we will restrict eligibility to patients between the ages of 18 and
- •Adequate hematologic, hepatic and renal function as defined below
- •Hemoglobin > or = to 8.0 g/dl
- •Absolute neutrophil count > or = to 1,500/mm3
- •Platelet count > or = to 100,000/mm3
- •Total Bilirubin < or = to1.5 x upper limit of normal (ULN).
- •ALT (SGOT) or AST (SGPT) < or = to 5 x ULN.
- •Alkaline Phosphatase < or = to 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases.
- •Serum creatinine 2.0 mg/dL
- •Ability to understand informed consent and comply with treatment protocol
- •Normal cardiac ejection fraction
- •Urine protein:creatinine (UPC) ratio < than or = to 1.0 at screening
排除标准
- •Uncontrolled intercurrent illness including infection or congestive heart failure within 6 months.
- •Prior therapy with gemcitabine, docetaxel or bevacizumab
- •Patients receiving other investigational agents
- •Patients with known brain metastases
- •Pregnancy or unwillingness to use effective birth control
- •Patients with HIV disease will be permitted, only if they are on effective anti-retroviral therapy, have a CD4 count greater than 400, and have had no opportunistic infections within the past 6 months.
- •Patients on anti-coagulation will be permitted if they are on a stable dose of warfarin or low-molecular weight heparin, and have had no major bleeds within the past 6 months.
- •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 bevacizumab cancer study
- •Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last three years
- •Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg lasting > 24 hours on antihypertensive medications)
- •Any prior history of hypertensive crisis or hypertensive encephalopathy
- •New York Heart Association (NYHA) Grade II or greater congestive heart failure
- •Significant vascular disease (e.g., aortic aneurysm, aortic dissection), requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- •Symptomatic peripheral vascular disease
- •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 study enrollment 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 study enrollment
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- •Serious, non-healing wound, active ulcer, or non-healing bone fracture
- •Proteinuria at screening as demonstrated by
- •Urine protein:creatinine (UPC) ratio > or = to 1.0 at screening (patients discovered to have UPC ratio > or = to 1.0 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
- •Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
- •History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3 months prior to study enrollment.
- •Any history of stroke or transient ischemic attack within 6 months
- •History of myocardial infarction or unstable angina within 6 months
研究组 & 干预措施
gemcitabine and docetaxel with bevacizumab
Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.
干预措施: gemcitabine (Drug)
gemcitabine and docetaxel with bevacizumab
Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.
干预措施: docetaxel (Drug)
gemcitabine and docetaxel with bevacizumab
Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.
干预措施: bevacizumab (Drug)
结局指标
主要结局
Overall Objective Response
时间窗: 6 months
Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
次要结局
未报告次要终点