Pharmacological Ascorbate Combined With Radiation and Temozolomide in Glioblastoma Multiforme: A Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive high-dose ascorbate in addition to the standard treatment.
详细描述
Standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). After radiation, patients receive additional cycles of temozolomide (adjuvant chemotherapy).
Participants will:
- receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase
- receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
- complete health-related quality of life questionnaires pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and then every 3 months. In addition, patients will complete neurocognitive testing pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and approximately 9 months after initiating radiation therapy.
The adjuvant chemotherapy portion of this study lasts for 6 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.
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
- •Ability to understand and willingness to sign informed consent (power of attorney and/or legally authorized representatives cannot sign on behalf of the patient)
- •Patients must have newly diagnosed (i.e., within 5 weeks), histologically or cytologically confirmed glioblastoma multiforme.
- •Diagnosis must be made by surgical biopsy or excision.
- •Therapy must begin ≤ 5 weeks after surgery or biopsy
- •Age ≥ 18 years
- •ECOG performance status 0-
- •(KPS > 50)
- •Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
- •Platelets ≥ 100,000 per mm3
- •Hemoglobin ≥ 8 g/dL
- •Creatinine ≤ 2.0 mg
- •Total bilirubin ≤ 1.5 mg/dL
- •ALT ≤ 3 times the institutional upper limit of normal
- •AST ≤ 3 times the institutional upper limit of normal
- •Tolerate one test dose (15g) of ascorbate.
- •Not pregnant.
排除标准
- •Recurrent high grade glioma
- •G6PD (glucose-6-phosphate dehydrogenase) deficiency.
- •Patients actively receiving insulin or using a finger-stick glucometer daily for blood glucose measurements
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide.
- •Significant co-morbid central nervous system disease, including but not limited to, multiple sclerosis.
- •Patients who are on the following drugs and cannot have a drug substitution: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
- •Known active concurrent malignancy, as determined by treating physicians.
- •Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma.
- •Prior radiation therapy to the head or neck resulting in overlap of RT fields.
- •Patients receiving any other investigational agents (imaging agents are acceptable)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would result in a hospital stay or delay of treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or impact patient safety.
- •Pregnant women.
- •Breastfeeding women.
- •Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.
研究组 & 干预措施
ascorbate, radiation, temozolomide
Concomitant therapy:
Radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions
Adjuvant therapy:
Oral temozolomide and pharmacological ascorbate (ascorbic acid) infusions
干预措施: Temozolomide (Drug)
ascorbate, radiation, temozolomide
Concomitant therapy:
Radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions
Adjuvant therapy:
Oral temozolomide and pharmacological ascorbate (ascorbic acid) infusions
干预措施: radiation therapy (Radiation)
ascorbate, radiation, temozolomide
Concomitant therapy:
Radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions
Adjuvant therapy:
Oral temozolomide and pharmacological ascorbate (ascorbic acid) infusions
干预措施: Ascorbic Acid (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: monthly up to 5 years post treatment
From radiation day 1 until date of death from any cause.
次要结局
- Adverse Event Frequency(monthly through 7 months post-radiation)
- Progression Free Survival (PFS)(monthly up to 5 years post treatment)
研究者
Bryan Allen
Assistant Professor, Radiation Oncology
University of Iowa