High-Dose Ascorbic Acid in Treating Patients with Newly Diagnosed Glioblastoma Multiforme Receiving Temozolomide and Undergoing Radiation Therapy
This trial is active, not recruiting.
|Conditions||glioblastoma, gbm, glioblastoma multiforme|
|Treatments||ascorbate, temozolomide, radiation therapy|
|Sponsor||University of Iowa|
|Collaborator||National Institutes of Health (NIH)|
|Start date||April 2013|
|End date||November 2015|
|Trial size||30 participants|
|Trial identifier||NCT01752491, 201211713, P30CA086862, U01CA140206|
This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for initial treatment of glioblastoma multiforme (GBM).
|Endpoint classification||safety study|
|Intervention model||single group assignment|
Number of grade 3, 4, & 5 adverse events
time frame: Weekly during therapy for up to 10 months
Time to progression
time frame: monthly up to 5 years post treatment
time frame: Up to 5 years
Male or female participants at least 18 years old.
Inclusion Criteria: - 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. - Age ≥ 18 years - ECOG performance status 0-2 (Karnofsky > 50%). - A complete blood count and differential must be obtained within 21 days prior to the first dose of radiation, with adequate bone marrow functions as defined below: - Absolute neutrophil count (ANC) ≥ 1500 cells per mm3 - Platelets ≥ 100,000 per mm3 - Hemoglobin ≥ 8 g/dL - Serum blood chemistries within 21 days before the first day of radiation, as defined below: - Creatinine ≤ 2.0 mg - Total bilirubin ≤ 1.5 mg/dL - ALT (Alanine Aminotransferase)≤ 3 times the institutional upper limit of normal - AST (Aspartate Aminotransferase) ≤ 3 times the institutional upper limit of normal - Tolerate one text dose (15g) of ascorbate - Not pregnant - Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: - Recurrent high grade glioma - G6PD (glucose-6-phosphate dehydrogenase) deficiency - Patients actively receiving insulin unless approved by the study medical monitor, study sponsor, and the study principal investigator. - 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: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs. - Prior invasive malignancies (except non-melanomatous skin cancers and carcinoma in situ of the cervix or bladder) unless disease free for ≥ 5 years. - Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma. - Prior radiation therapy to the head or neck, which would result in overlap of radiation therapy fields. - Patients may not be receiving any other investigational agents. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant women are excluded from this study because ionizing radiation is a known teratogen, and temozolomide is a Class D agent with the potential for teratogenic or abortifacient effects. - Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 (an enzyme pathway) inducer, which results in lower serum levels of antiretroviral drugs
|Official title||A Phase I Trial of High-Dose Ascorbate in Glioblastoma Multiforme|
|Principal investigator||John M. Buatti, MD|
|Description||This phase 1 study will test the safety of adding high dose ascorbate (vitamin C) to standard chemoradiation and, after the radiation is completed, during 6 cycles of temozolomide. Standard treatment for glioblastoma multiforme (GBM) involves surgery followed by radiation combined with temozolomide (a chemotherapy). After radiation, patients receive cycles of temozolomide (adjuvant chemotherapy) Participants will: - receive high doses of intravenous (IV) ascorbate three times a week during chemoradiation - receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation) This is a phase 1 study will evaluate the side effects of adding this drug to the standard therapy. The dose given to a participant will be determined by how well other participants have tolerated the drug.|
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