A Phase II Trial of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Who Have Failed Whole Brain Radiation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 7
- 主要终点
- Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab
研究概览
简要总结
This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease has spread to their brain. This study will not evaluate the effect of bevacizumab on the systemic solid tumor cancer. Bevacizumab is a medication and it is thought that bevacizumab may interfere with the growth of new blood vessels; therefore it might stop tumor growth and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels.
详细描述
PRIMARY OBJECTIVES:
I. Determine the radiographic response rate in patients with solid tumor brain metastases treated with bevacizumab.
SECONDARY OBJECTIVES:
I. Estimate the progression-free survival (PFS) rate at 6 months. II. Determine the time to progression based on magnetic resonance imaging (MRI) or computed tomography (CT) scans.
III. Determine the time to response based on radiographic imaging. IV. Determine the duration of response based on radiographic imaging. V. Determine overall survival. VI. Collect additional safety data. VII. Assess changes in quality of life using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) while on treatment.
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
- •Patients must have a histologically or cytologically confirmed non-central nervous system (CNS) primary solid malignancy at the time of initial diagnosis; NOTE: brain lesions are not required to have pathologic confirmation; in addition, a copy of the pathology report for the primary tumor is sufficient for registration purposes
- •Patients must have radiographically-confirmed recurrent brain metastases from a solid tumor after WBRT
- •Patients must have measurable or evaluable disease in the brain
- •Patients must have been on a stable dose of corticosteroids >= 5 days prior to obtaining their baseline gadolinium (Gd)-MRI of brain
- •Patients must have completed WBRT > 12 weeks prior to enrollment to limit cases of pseudoprogression; however if new lesions are noted < 12 weeks but > 4 weeks prior to enrollment, those patients are eligible
- •Patients who underwent radiosurgery to treat a progressive lesion must have confirmation of tumor by tissue, magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion or positron emission tomography (PET) and the lesion must be measurable; NOTE: radiosurgery may be done to a lesion that will not be used for response evaluation and should be done > 2 weeks prior to enrollment
- •Patients may be on other systemic chemotherapies if progressive CNS disease occurs while on these treatments; NOTE: new systemic chemotherapies should not be started unless required to treat systemic disease and should not start until at least 1 follow up imaging study has been performed
- •Patients may have received any number of prior CNS directed therapies - there are no limitations
- •Patients must have a life expectancy of >= 12 weeks
- •Patients must have a Karnofsky performance score (KPS) of >= 60
- •Whole blood cell (WBC) >= 3,000/ul
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Hemoglobin >= 10 gm/dl (may be reached by transfusion)
- •Serum glutamic oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) (or < 5 x ULN if liver is involved)
- •Bilirubin < 2 x ULN (or < 5 x ULN if liver is involved)
- •Creatinine < 1.5 x ULN
- •Patients of both sexes must agree to the use of barrier contraceptives throughout the duration of treatment on this trial and for 3 months after discontinuing treatment; NOTE: hormonal contraceptives are not acceptable as a sole method of contraception
- •Patients must be > 4 weeks from any major surgery
- •Patients NOT on warfarin must have a prothrombin time (PT)/international normalized ratio (INR) < 1.4 within 14 days prior to registration
- •Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW] heparin) must meet BOTH of the following criteria within 14 days prior to registration:
- •No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- •In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of LMW heparin
- •Female patients of child-bearing potential must have a negative pregnancy test within 14 days prior to registration
- •Patients must be willing and able to comply with study and/or follow-up procedures
- •Patients must sign an informed consent prior to registration and before undergoing any study-specific procedures indicating that they are aware of the investigational nature of this study
排除标准
- •Patients with a diagnosis of intrathoracic lung carcinoma of squamous cell histology are not eligible for participation
- •Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using barrier birth control methods, are not eligible for participation
- •Patients must not have baseline proteinuria within 14 days prior to registration as demonstrated by either:
- •Urine protein: creatinine (UPC) ratio < 1.0 at screening, OR
- •Urine dipstick for proteinuria =< 2+; NOTE: 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
- •Patients must not have experienced any major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or be anticipated to need a major surgical procedure during the course of the study; NOTE: the exception is craniotomy
- •Patients must not have experienced a core biopsy or other minor surgical procedure within 7 days prior to registration; NOTE: this excludes placement of a vascular access device
- •Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the previous 6 months are not eligible for participation
- •Patients with a serious, non-healing wound, ulcer, or bone fracture are not eligible for participation due to the effects on vasculature by bevacizumab which may impair healing
- •Patients known to be human immunodeficiency virus (HIV) or hepatitis B and/or C positive are not eligible for participation; NOTE: HIV and hepatitis testing is not required for study participation
- •Patients with a history of any other cancer (except for non-melanoma skin cancer or carcinoma in-situ of the cervix), are not eligible for participation unless they are in complete remission and have been off of all therapy for that disease for a minimum of 3 years
- •Patients receiving or participating on any other experimental agents/clinical trials are not eligible for participation
- •Patients with a known hypersensitivity to any component of bevacizumab are not eligible for participation
- •Patients with any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation
- •Patients with leptomeningeal disease are not eligible for participation
- •Patients who have received previous treatment with bevacizumab for CNS disease are not eligible for participation
- •Patients with inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg) are not eligible for participation
研究组 & 干预措施
Treatment (bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
Treatment (bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes every 2 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: bevacizumab (Biological)
结局指标
主要结局
Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab
时间窗: Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.
Radiographic Response to treatment will be assessed prior to every odd-numbered cycle using CT or MRI scans until disease progression, unacceptable toxicity as assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as the number of patients with Complete Response (CR) plus those with Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.
次要结局
- Progression-Free Survival (PFS) at 6 Months in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(At 6 months from treatment initiation.)
- Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases(Assessed prior to every cylcle (cycle=28 days) while on treatment through 30 days post last dose. Range of cycles 1-20.)
- Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(From documentation of response, every two cycles (1 cycle =28 days) until progressive disease. Range of cycles completed 1-20.)
- Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(From treatment initiation, every 2 cycles (1 cycle = 28 days) until progressive disease. Range of cycles completed 1-20.)
- Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(Baseline and at Cycle 3 (1 Cycle = 28 days).)
- Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(From the start of treatment every 2 cycles (1 cycle =28 days) until time of response. Range of cycles completed 1-20.)
- Overall Survival (OS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab(From start of treatment until death from any cause. Median follow up of 8 months (range 1.3 to 47.9 months))