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

NCT04900792 | Active Not Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 2021031251R21CA270742
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Glioblastoma Multiforme

Keywords

ascorbate; radiation therapy; temozolomide; ferumoxytol

Outcome Measures

Primary Outcomes (1)

• Determination of recommended phase 2 ferumoxytol dosing regimen

  The recommended dose will be determined by incidence of dose limiting toxicities.

  From treatment day 1 through 12 weeks after completing radiation

Secondary Outcomes (6)

• Estimate progression free survival (PFS)

  From treatment day 1 to disease progression, up to 60 months post-treatment

• Estimate overall survival (OS)

  Time (measured in days) until death from any cause, up to 20 years post-treatment

• Estimate Objective Response Rate (ORR)

  12 weeks post-radiation

• Tumor size

  Baseline and 12 weeks post-radiation

• Clinical response

  12 weeks post-radiation

Study Arms (2)

Cohort 1 (starting)

EXPERIMENTAL

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.

Drug: Ferumoxytol injection; Drug: Pharmacological ascorbate; Radiation: External beam radiation therapy; Drug: Temozolomide

Cohort 2

EXPERIMENTAL

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

Drug: Ferumoxytol injection; Drug: Pharmacological ascorbate; Radiation: External beam radiation therapy; Drug: Temozolomide

Interventions

Ferumoxytol injection 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.

Also known as: Feraheme, Ferumoxytol

Cohort 1 (starting); Cohort 2

Temozolomide 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.

Also known as: Temodar, temozolomide capsule

Cohort 1 (starting); Cohort 2

External beam radiation therapy RADIATION

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

Also known as: EBRT, radiotherapy, VMAT

Cohort 1 (starting); Cohort 2

Pharmacological ascorbate DRUG

Intravenous ascorbate

Also known as: ASCOR, vitamin C, ascorbic acid

Cohort 1 (starting); Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bryan Allen: lead
• Holden Comprehensive Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Department of Radiation Oncology at University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• 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.

  PMID: 31427282 BACKGROUND

• 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.

  PMID: 28366679 BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

Ferrosoferric Oxide; Ascorbic Acid; Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Therapeutics; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• John M. Buatti, MD

  University of Iowa

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 16, 2021
• First Posted: May 25, 2021
• Study Start: February 28, 2023
• Primary Completion: May 13, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Study protocol and informed consent will be shared after primary completion. Statistical analysis plan will be shared with results reporting.
• Access Criteria: An IRB-stamped signed usage agreement will be required in addition to a data sharing agreement between the academic centers.

Locations

US (1)