A Phase I Study of Bevacizumab and Intravenous Ascorbic Acid for Patients With Recurrent High Grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Incidence of dose limiting toxicities (DLT)
研究概览
简要总结
This phase I trial studies the side effects and best dose of ascorbic acid when given together with bevacizumab in treating patients with high grade glioma that has come back (recurrent). Monoclonal antibodies, such as bevacizumab may interfere with the ability of tumor cells to grow and spread. Ascorbic acid contains ingredients that may prevent or slow the growth of high grade glioma. Giving bevacizumab and ascorbic acid together may work better in treating patients with high grade glioma.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the toxicities and determine the recommended dose of intravenous ascorbic acid given three times weekly in combination with intravenous bevacizumab every two weeks in patients with recurrent high grade glioma.
SECONDARY OBJECTIVES:
I. To evaluate changes in the levels of serum ascorbic acid (using high performance liquid chromatography [HPLC] with coulometric electrochemical detection) during therapy with ascorbic acid and bevacizumab.
II. Radiographic assessment of disease status after 2 cycles of therapy with ascorbic acid and bevacizumab.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have pathologically proven diagnosis of high grade glioma
- •Patients must have received prior radiation therapy and standard temozolomide; patients who have received additional therapies for previous progressions will be considered eligible
- •Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
- •Patients must have recovered from toxicity of prior therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Hemoglobin >= 8 g/dL
- •Platelet count >= 100,000/mm^3
- •Serum creatinine that is at or below 2.0 mg/dL
- •Serum aspartate transaminase (AST) and alanine transaminase (ALT) less than 1.5 times the upper limits of normal
- •Serum alkaline phosphatase less than 2.5 times the upper limits of normal
- •The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
- •Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
- •Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)
排除标准
- •History of uncontrollable allergic reactions to bevacizumab or ascorbic acid
- •Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active antiretroviral therapy (HAART)
- •History of glucose-6-phosphate dehydrogenase deficiency
- •History of oxalate nephrolithiasis or urine oxalate >60 mg/dL
- •Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input
- •Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab
- •Clinically significant cardiovascular disease defined as follows:
- •Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic pressure [DBP] > 90 mm Hg despite antihypertensive therapy)
- •History of cerebrovascular accident (CVA) within 6 months
- •Myocardial infarction or unstable angina within 6 months
- •Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed
- •Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration
- •Major surgical procedure, open biopsy or significant traumatic injury =< 28 days prior to registration
- •Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
- •Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide; Note: high dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
- •Simultaneous participation in other therapeutic clinical trials will not be allowed
- •Inability to co-operate with the requirements of the protocol
- •Pregnant and nursing women are excluded from this study
结局指标
主要结局
Incidence of dose limiting toxicities (DLT)
时间窗: Up to 56 days
Described by dose level
Maximum tolerated dose of ascorbic acid combined with bevacizumab
时间窗: Up to 56 days
Maximum tolerated dose of ascorbic acid in combination with bevacizumab defined as the highest dose tested which results in DLT in no more than 1 of 6 evaluable patients
Frequency of occurrence of overall toxicity
时间窗: Up to 52 weeks
Categorized by toxicity grades
Incidence rates of adverse events
时间窗: Up to 52 weeks
Described by dose level
次要结局
- QOL using EORTC QLQ-C30(Up to 52 weeks)
- Disease status by radiologic assessment(Up to 56 days)
- Survival(First date of therapy until the date of death from any cause, assessed up to 1 year)
- Changes in serum levels of ascorbic acid using HPLC with coulometric electrochemical detection(Week 1 to up to Week 52)
- Progression free survival(First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 1 year)