A Phase I Study of Metronomic Temozolomide 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
- 4
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide
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 temozolomide in treating patients with high-grade glioma that has come back. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ascorbic acid contains ingredients that may prevent or slow the growth of high-grade gliomas. Giving temozolomide with ascorbic acid may kill more tumor cells.
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 temozolomide 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 temozolomide.
II. Radiographic assessment of disease status after 2 cycles of therapy with ascorbic acid and temozolomide.
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 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) count >= 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 aminotransferase (AST) and alanine aminotransferase (ALT) less than 1.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
- •Serum alkaline phosphatase less than 2.5 times the upper limits of normal; note: if hepatic function is abnormal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
- •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 temozolomide or ascorbic acid or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
- •Known human immunodeficiency virus (HIV)-positivity AND actively being treated with highly active anti-retroviral 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 since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity
- •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
研究组 & 干预措施
Treatment (ascorbic acid, temozolomide)
Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: ascorbic acid (Dietary Supplement)
Treatment (ascorbic acid, temozolomide)
Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temozolomide (Drug)
Treatment (ascorbic acid, temozolomide)
Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Other)
Treatment (ascorbic acid, temozolomide)
Patients receive ascorbic acid IV over 90-120 minutes three times per week and temozolomide orally days 1-28. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum Tolerated Dose of Ascorbic Acid in Combination With Temozolomide
时间窗: 56 days
Maximum tolerated dose of ascorbic acid in combination with temozolomide, defined as the highest dose tested which results in dose limiting toxicity (DLT) in no more than one of six evaluable patients. Graded by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 4.0. DLT incidence will be described by dose level.
Incidence Rates of Adverse Events, Graded According to the NCI Common Toxicity Criteria for Adverse Events Version 4.0
时间窗: Up to 30 days after last administration of study medication
The incidence rates of adverse events will be described by dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.
次要结局
- Using Radiologic Measurements for Tumor Response(Up to 52 weeks)
- Changes in Serum Levels of Ascorbic Acid Using High-performance Liquid Chromatography (HPLC) With Coulometric Electrochemical Detection)(Baseline to up to 52 weeks)