Pharmacologic Ascorbate and Ferumoxytol Combined with Temozolomide and Radiation Therapy for the Treatment of Newly Diagnosed Glioblastoma

Inclusion Criteria

• Willingness and ability to provide informed consent consistent with Good Clinical Practice (i.e., legally authorized representative will not be used / allowed for this study).
• Stated willingness to comply with all study procedures for the duration of the study
• Stated willingness to have a central venous access device (e.g., CVAD, infusion port) placed
• Aged 18 years or older
• Newly diagnosed (i.e., within 6 weeks), histologically or molecularly confirmed glioblastoma or diffuse midline glioma
• Therapy to begin within 6 weeks of last surgery
• Able to take oral medication
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky Performance Scale [KPS] of > 50)
• Medically fit, as determined by prescribing oncologists, to undergo temozolomide and radiation therapy
• Agree to use of contraception from screening until at least 90 days after the last study treatment (study participant should not discontinue contraception until discussing with their treating oncologist(s))
• Not have significant co-morbid central nervous system disease, such as multiple sclerosis
• Agree to Lifestyle Considerations throughout study duration
• Current use of antiretroviral drugs (e.g., nelfinavir, abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine). Pharmacologic ascorbate acid a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs

Exclusion Criteria

• Current use of the following drugs and cannot have a drug substitution or decline the drug substitution: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide. Pharmacologic ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs
• Insulin requirement
• Requires blood glucose monitoring using finger-stick glucose checks
• Medical requirement or indication for iron supplementation (including ferumoxytol, ferrous gluconate, ferrous fumarate, or ferrous sulfate). NOTE: Over the counter, patient-elective supplementation is acceptable
• Inability to undergo MR imaging
• Inability to tolerate a 15g test dose of ascorbate
• Pregnancy or lactation (note: potential participants should not engage in ‘pump & dump’ strategy; lactation must be discontinued)
• Known allergic reaction to ferumoxytol
• History of Stevens Johnson Syndrome
• History of hemochromatosis
• Prior radiation treatment that would result in field overlap. For potential participants who have undergone nuclear medicine therapy, including peptide receptor radionuclide therapy (PRRT), the study’s radiation oncologist must approve study entry
• G6PD (glucose-6-phosphate dehydrogenase) deficiency
• Platelet count < 100,000 /mm^3 within 21 days of first treatment
• Creatinine >= 1.5 x the institutional upper limit of normal within 21 days of the first treatment or if creatinine is elevated a creatinine clearance of < 60 mL/(min 1.73 m^2)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring inpatient admission or a delay to start of therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Treatment with another investigational drug within 30 days prior to study treatment day 1. Imaging trials (including investigational positron emission tomography [PET] or nuclear medicine [NM] tracers) as well as observational trials are acceptable
• Clinical trials with an endpoint of treating the patient’s cancer, including behavioral, nutritional, and/or device human subject studies