A Safety Study of Pharmacologic Ascorbate and Ferumoxytol in Addition to Standard of Care Chemoradiation in Glioblastoma (XACT-Fe-GBM-01)

June 21, 2026 updated by: Bryan Allen

A First-in-Human Clinical Trial of Pharmacologic Ascorbate and Ferumoxytol Combined With Concomitant Temozolomide and External Beam Radiation Therapy for Newly Diagnosed Glioblastoma

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Department of Radiation Oncology at University of Iowa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • Feraheme
  • Ferumoxytol
Drug: Pharmacological ascorbate
Intravenous ascorbate
Other Names:
  • ascorbic acid
  • vitamin C
  • ASCOR
Radiation: External beam radiation therapy
Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.
Other Names:
  • EBRT
  • radiotherapy
  • VMAT
Drug: 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.
Other Names:
  • Temodar
  • temozolomide capsule
Experimental: 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
Drug: 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.
Other Names:
  • Feraheme
  • Ferumoxytol
Drug: Pharmacological ascorbate
Intravenous ascorbate
Other Names:
  • ascorbic acid
  • vitamin C
  • ASCOR
Radiation: External beam radiation therapy
Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.
Other Names:
  • EBRT
  • radiotherapy
  • VMAT
Drug: 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.
Other Names:
  • Temodar
  • temozolomide capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Ferumoxytol-related Dose Limiting Toxicities (DLTs)
Time Frame: From treatment day 1 through 12 weeks after completing radiation
The recommended dose will be determined by incidence of dose limiting toxicities.
From treatment day 1 through 12 weeks after completing radiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimate Progression Free Survival (PFS)
Time Frame: From treatment day 1 to disease progression, up to 16 months post-treatment
Time (measured in months) to documented disease progression in MRI imaging as described by the RANO criteria.
From treatment day 1 to disease progression, up to 16 months post-treatment
Estimate Overall Survival (OS)
Time Frame: Time (measured in months) until death from any cause, up to 26 months post-treatment
Time to death from any cause.
Time (measured in months) until death from any cause, up to 26 months post-treatment
Disease Response
Time Frame: 12 weeks post-radiation
Disease response and tumor measurements over time were assessed using Response Assessment in Neuro-Oncology (RANO) criteria in conjunction with the Neurologic Assessment in Neuro-Oncology (NANO) beginning 12 weeks after completion of radiation therapy, using radiation simulation MRI/CT as baseline. RANO disease response categories included complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Tumor measurements obtained during radiographic assessment were incorporated into the overall RANO response evaluation.
12 weeks post-radiation
Number of Participants With Treatment-Related Adverse Events
Time Frame: Up to 36 months post-radiation
Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (v5). Treatment-related adverse events were categorized by toxicity type, including liver function, hematologic, and non-hematologic events. Participants were counted once per toxicity category if they experienced at least one treatment-related adverse event within that category during the study period.
Up to 36 months post-radiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bryan Allen

Collaborators

National Cancer Institute (NCI)
Holden Comprehensive Cancer Center

Investigators

  • Study Director: John M. Buatti, MD, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2023

Primary Completion (Actual)

May 13, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 16, 2021

First Submitted That Met QC Criteria

May 19, 2021

First Posted (Actual)

May 25, 2021

Study Record Updates

Last Update Posted (Actual)

July 20, 2026

Last Update Submitted That Met QC Criteria

June 21, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202103125
  • 1R21CA270742 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.

IPD Sharing Time Frame

Study protocol and informed consent will be shared after primary completion. Statistical analysis plan will be shared with results reporting.

IPD Sharing Access Criteria

An IRB-stamped signed usage agreement will be required in addition to a data sharing agreement between the academic centers.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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