A Safety Study of Pharmacologic Ascorbate and Ferumoxytol in Addition to Standard of Care Chemoradiation in Glioblastoma

NCT ID: NCT04900792

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-28
• Study Completion Date: 2026-12-31

Brief Summary

This clinical trial evaluates adding ferumoxytol and pharamcologic ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive ferumoxytol and pharmacologic ascorbate in addition to the standard treatment.

Detailed Description

The initial, standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth).

Participants in this trial will:

• receive intravenous (IV) ferumoxytol the day before starting radiation, then around radiation treatments 6, 25, and 31.
• receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase.
• provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.

Conditions

Glioblastoma; Glioblastoma Multiforme

Keywords

ascorbate; radiation therapy; temozolomide; ferumoxytol

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (starting)

Radiation Phase

• Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
• Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
• Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
• Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).

Adjuvant Phase

• Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
• Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
• Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.

Group Type: EXPERIMENTAL

Ferumoxytol injection

Intervention Type: DRUG

Ferumoxytol is an iron replacement product FDA approved for treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). This trial uses the FDA approved dosage (512 mg iron) for iron-deficiency anemia in CKD.

Pharmacological ascorbate

Intervention Type: DRUG

Intravenous ascorbate

External beam radiation therapy

Intervention Type: RADIATION

Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.

Temozolomide

Intervention Type: DRUG

Temozolomide is a cytotoxic alkylating agent administered orally that penetrates well into the central nervous system. It is a standard-of-care treatment for GBM.

Cohort 2

Radiation Phase

• Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
• Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
• Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
• Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).

Adjuvant Phase

• Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
• Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
• Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of

Group Type: EXPERIMENTAL

Ferumoxytol injection

Intervention Type: DRUG

Ferumoxytol is an iron replacement product FDA approved for treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). This trial uses the FDA approved dosage (512 mg iron) for iron-deficiency anemia in CKD.

Pharmacological ascorbate

Intervention Type: DRUG

Intravenous ascorbate

External beam radiation therapy

Intervention Type: RADIATION

Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.

Temozolomide

Intervention Type: DRUG

Temozolomide is a cytotoxic alkylating agent administered orally that penetrates well into the central nervous system. It is a standard-of-care treatment for GBM.

Interventions

Ferumoxytol injection

Ferumoxytol is an iron replacement product FDA approved for treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). This trial uses the FDA approved dosage (512 mg iron) for iron-deficiency anemia in CKD.

Intervention Type: DRUG

Pharmacological ascorbate

Intravenous ascorbate

Intervention Type: DRUG

External beam radiation therapy

Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.

Intervention Type: RADIATION

Temozolomide

Temozolomide is a cytotoxic alkylating agent administered orally that penetrates well into the central nervous system. It is a standard-of-care treatment for GBM.

Intervention Type: DRUG

Other Intervention Names

Feraheme; Ferumoxytol; ASCOR; vitamin C; ascorbic acid; EBRT; radiotherapy; VMAT; Temodar; temozolomide capsule

Eligibility Criteria

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
• 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
• ECOG performance status of 0, 1, or 2 (KPS of >50)
• Recommended to receive temozolomide and radiation therapy
• Medically fit, as determined by the prescribing oncologists, to undergo temozolomide and radiation therapy.
• Agree to use of highly effective 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

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 ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs.
• Current use of antiretroviral drugs (e.g., nelfinavir, abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine). Pharmacologic ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral 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.
• Pregnancy or lactation (note: potential participants should not engage in 'pump & dump' strategy; lactation must be discontinued).
• Known allergic reactions to ferumoxytol.
• History of Steven's Johnson Syndrome
• History of hemochromatosis.
• Prior radiation treatment that would result in field overlap. For potential participants who have undergone nuclear medicine therapy, including PRRT, the study's radiation oncologist must approve study entry.
• G6PD (glucose-6-phosphate dehydrogenase) deficiency
• Platelet count < 100,000 /mm3 within 21 days of first treatment
• Creatinine ≥ 1.5x 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 m2)
• 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 PET or 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Holden Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Bryan Allen

OTHER

Sponsor Role: lead

Responsible Party

Bryan Allen

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John M. Buatti, MD

Role: STUDY_DIRECTOR

University of Iowa

Locations

Department of Radiation Oncology at University of Iowa

Iowa City, Iowa, United States

Countries

United States

References

Allen BG, Bodeker KL, Smith MC, Monga V, Sandhu S, Hohl R, Carlisle T, Brown H, Hollenbeck N, Vollstedt S, Greenlee JD, Howard MA, Mapuskar KA, Seyedin SN, Caster JM, Jones KA, Cullen JJ, Berg D, Wagner BA, Buettner GR, TenNapel MJ, Smith BJ, Spitz DR, Buatti JM. First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma. Clin Cancer Res. 2019 Nov 15;25(22):6590-6597. doi: 10.1158/1078-0432.CCR-19-0594. Epub 2019 Aug 19.

Reference Type: BACKGROUND

PMID: 31427282 (View on PubMed)

Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30.

Reference Type: BACKGROUND

PMID: 28366679 (View on PubMed)

Other Identifiers

1R21CA270742

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202103125

Identifier Type: -

Identifier Source: org_study_id