Avastin and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme: A Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 5
- 主要终点
- Objective Response
研究概览
简要总结
This study is being conducted to help determine whether the addition of Avastin (an anti-cancer drug), when given along with temozolomide during the monthly cycles that follow radiation, is able to delay tumor growth, shrink tumors, or impact how long people with GBM live. This study is sponsored by Genentech, Inc., the manufacturer of Avastin.
Avastin is the experimental drug being administered in this research study. Avastin binds a protein called vascular endothelial growth factor, or VEGF. VEGF is produced by tumors and circulates in the blood. One of VEGF's main roles is to support the growth of new blood vessels. During cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells and help them grow. Avastin binds to VEGF, which then prevents VEGF from functioning. In laboratory studies, Avastin prevented the growth of several different types of cancer cells grown in animals. Avastin was approved by the Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer in combination with chemotherapy. Avastin has not been approved by the FDA for the treatment of GBM and is, therefore, considered experimental. Avastin is currently undergoing testing (alone and in combination with another anti-cancer drug, irinotecan) in persons with GBM that have come back after conventional treatment.
Temozolomide (Temodar) is an anti-cancer drug that works by interfering with the growth of cells (including cancer cells) by stopping their division. Temozolomide was approved by the U.S. FDA for the treatment of newly diagnosed GBM in 2005.
Avastin and temozolomide are currently being used together in several research studies involving people with newly diagnosed GBM. Limited information is available about either the safety or effectiveness of this drug combination.
详细描述
The study consists of the following: 1) a screening period of up to 28 days; 2) a treatment period of radiation with daily temozolomide that lasts approximately 6 weeks, 3) a study treatment period that will last until either your tumor grows or you experience unacceptable side effects; and 4) a 30-day follow-up period after treatment has ended. Additionally, basic information concerning your condition will be collected every 2 months after the follow-up period for the rest of your life.
During this study, Dr. Nicholas and his research team will collect information about you for the purposes of this research. This includes name, address, dates (i.e., date of birth, date of consent), telephone number, and medical record number. Slides of your tumor tissue that were used to diagnose your GBM will be sent to a pathologist to confirm the diagnosis of GBM. After this review has been completed your slides will be returned to the hospital that provided them. Preserved samples of your tumor will also be sent for a test to determine how effective the temozolomide might be in your case. Any remaining tissue will be returned to the hospital that provided it.
Screening phase (following diagnosis of GBM at surgery) To determine if you are eligible to participate in this study, you will undergo a screening process that will involve the following
- Assessment of your cancer by magnetic resonance imaging (MRI) of your brain using an intravenous (in your vein) contrast material
- Recording of your general medical, surgical and cancer history
- Physical examination, including measurement of your blood pressure, height and weight
- Evaluation of your performance status (your ability to carry on daily activities)
- Neurologic examination (how well your nerves and muscles work)
- Blood sample for laboratory tests (approximately 2 to 3 tablespoons) to evaluate your blood counts, liver, and kidney function
- Serum pregnancy test if you are a woman of childbearing potential
- Urine sample
- Recording of any medications taken within the past 14 days
Radiation and daily temozolomide chemotherapy You will begin radiation treatment within 5 weeks of surgery. You will take temozolomide orally once daily (seven days a week) during radiation treatments (which occur Monday - Friday and last approximately six weeks). You will take a medication to prevent a rare form of pneumonia (pneumocystis carinii) that can occur when temozolomide is given on a daily basis. That may be either in pill form or inhaled. During radiation treatment you will be seen every two weeks by a study doctor at which time you will be asked how you are tolerating the treatment. A physical examination, (including neurological evaluation), will be performed. Blood tests (1-2 tablespoons) will be performed to assure that you are not having any side-effects from the chemotherapy.
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
- •Disease-Specific Concerns Histologically confirmed GBM as determined by central pathology review Supratentorial location
- •General Medical Concerns 18 years of age; Karnofsky performance status > 60; Tumor-related contrast enhancement on initial and post-operative Gd-MRI; Recovery from effects of surgery and/or its complications prior to initiating radiotherapy; Radiotherapy must begin < 5 weeks following surgery; Pre-and post-operative Gd-MRI prior to the initiation of radiotherapy; Adequate hematological, renal, and hepatic function:hemoglobin > 10 grams hematocrit > 30%, platelets > 100,000 per mm3, BUN < 25 mg/dl, Creatinine < 1.5 mg/dl, Total bilirubin < 1.5 mg/dl, SGOT or SGPT < twice institutional normal range, Subjects must not be pregnant or nursing, Use of effective means of contraception (men and women) in subjects of child-bearing (women) and at all ages (men), Study-specific signed informed consent, Ability to comply with study follow-up procedures.
排除标准
- •a. Disease-Specific Concerns: malignant gliomas graded less than GBM; infratentorial tumor location; recurrent disease; intra-tumoral hemorrhage; Placement of Gliadel® wafers; b. Bevacizumab-Specific Concerns: Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications); Any prior history of hypertensive crisis or hypertensive encephalopathy; History of myocardial infarction or unstable angina within 6 months prior to study enrollment; History of stroke or transient ischemic attack within 6 months prior to study enrollment; New York Heart Association (NYHA) Grade II or greater CHF (see Appendix E); Significant vascular disease (e.g., aortic aneurysm, aortic dissection); Symptomatic peripheral vascular disease; Evidence of bleeding diathesis or coagulopathy; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment; History of intracerebral abscess within 6 months prior to study enrollment; Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (exclusive of craniotomy); 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; Serious non-healing wound, ulcer, or bone fracture; Proteinuria at screening as demonstrated by either; 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); Known hypersensitivity to any component of Avastin. c. General Medical Exclusions
- •Subjects meeting any of the following criteria are ineligible for study entry:
- •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; History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix);Pregnant or nursing females; Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmias requiring medication;
- •Screening clinical laboratory values:
- •Absolute neutrophil count < 1500/ul, Platelet count < 100,000/ul, Total bilirubin > 1.6 mg.dl, AST/ALT > 1.5 x the upper limit of normal ( ULN), Creatinine > 1.2 x ULN, Urine protein/creatinine ratio > 1.0, International normalized ration (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 x ULN (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted.
研究组 & 干预措施
one
This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).
干预措施: Bevacizumab and Temozolomide (Drug)
结局指标
主要结局
Objective Response
时间窗: Up to 3 years
The best clinical response rates determined and 95% confidence intervals obtained using the exact binomial distribution.
Progression-free Survival (PFS)
时间窗: Up to 3 years
次要结局
- Duration of Response(Up to 2 years)
- Changes in Relative Cerebral Blood Volume (rCBV) of Tumors After (2 Infusions) of Avastin(Up to 3 years)
- Safety of Avastin in Combination With Temozolomide in This Study Population(Up to 3 years)
- Overall Survival(Up to 3 years)