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.
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. III. To evaluate progression-free and overall survival of patients with recurrent high grade glioma treated with therapy with ascorbic acid and bevacizumab. Patients with stable or responsive disease after every 2 cycles will continue on therapy with ascorbic acid and bevacizumab until intolerance or progressive disease. IV. To descriptively examine quality of life (QOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire QLQ-C30 during treatment. OUTLINE: This is a dose-escalation study of ascorbic acid. Patients receive ascorbic acid intravenously (IV) over 90-120 minutes three times per week (at least 24 hours apart) and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given IV
Given intravenously (IV)
Correlative studies
University of Nebraska Medical Center
Omaha, Nebraska, United States
Frequency of occurrence of overall toxicity
Categorized by toxicity grades
Time frame: Up to 52 weeks
Incidence of dose limiting toxicities (DLT)
Described by dose level
Time frame: Up to 56 days
Incidence rates of adverse events
Described by dose level
Time frame: Up to 52 weeks
Maximum tolerated dose of ascorbic acid combined with bevacizumab
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
Time frame: Up to 56 days
Changes in serum levels of ascorbic acid using HPLC with coulometric electrochemical detection
Correlation of intracellular glutathione with ascorbic acid levels during therapy with ascorbic acid and temozolomide will be summarized using descriptive statistics to summarize changes over time.
Time frame: Week 1 to up to Week 52
Disease status by radiologic assessment
Disease status measured by radiologic assessment
Time frame: Up to 56 days
Progression free survival
Will be plotted following the method of Kaplan and Meier
Time frame: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 1 year
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Enrollment
9
Ancillary studies
QOL using EORTC QLQ-C30
Will be descriptively summarized using means and standard deviations.
Time frame: Up to 52 weeks
Survival
Will be plotted following the method of Kaplan and Meier.
Time frame: First date of therapy until the date of death from any cause, assessed up to 1 year