Glioblastoma, GBM, Glioblastoma Multiforme
Conditions
Keywords
Ascorbate, Ascorbic acid, Vitamin C, Radiation, Temozolomide
Brief summary
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).
Detailed 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.
Interventions
DRUGAscorbate
Intravenous infusion of high-dose ascorbate
DRUGTemozolomide
Oral chemotherapeutic
RADIATIONRadiation therapy
External beam radiation therapy
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Joseph J. Cullen, MD, FACS
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of grade 3, 4, & 5 adverse events | Weekly during therapy for up to 10 months | Assess grade 3 and higher adverse events. Evaluate the frequency and severity against the published literature to determine the likely causality between ascorbate and the adverse event(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression | monthly up to 5 years post treatment | Time from the start of therapy (day 1, cycle 1) to documented disease progression in MRI imaging as described by MacDonald and colleagues. |
| Overall survival | Up to 5 years | From start of treatment (cycle 1, day 1) until the date of death from any cause. |
Countries
United States
Outcome results
None listed