A Phase I Trial of High-Dose Ascorbate in Glioblastoma Multiforme

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Joseph J. Cullen, MD, FACS; University of Iowa
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Treatments: Ascorbic Acid; Dacarbazine; Temozolomide; Vitamins

Criteria

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