A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma Multiforme

NCT02344355 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 201504786
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Glioblastoma Multiforme

Keywords

Ascorbic Acid; temozolomide; radiation

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  From radiation day 1 until date of death from any cause.

  monthly up to 5 years post treatment

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  monthly up to 5 years post treatment

• Adverse Event Frequency

  monthly through 7 months post-radiation

Other Outcomes (1)

• Health-related Quality of Life (HRQOL)

  monthly for 3 months, then every 3 months up to 5 years post treatment

Study Arms (1)

ascorbate, radiation, temozolomide

EXPERIMENTAL

Concomitant therapy: Radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions Adjuvant therapy: Oral temozolomide and pharmacological ascorbate (ascorbic acid) infusions

Drug: Temozolomide; Radiation: radiation therapy; Drug: Ascorbic Acid

Interventions

Temozolomide DRUG

oral temozolomide (75 mg/m2), given 7 days per week, for a maximum of 49 days during radiation therapy. Starting 1 month after radiation therapy, additional temozolomide will be given as chemotherapy cycles. Each cycle is 28 days. For the first cycle, temozolomide will be administered (150 mg/m2) once per day for 5 days. If the subject tolerates the first cycle well, temozolomide will be prescribed at 200 mg/m2 for cycles 2 through 6. Each cycle is 28 days.

Also known as: Temodar, Temodal

ascorbate, radiation, temozolomide

radiation therapy RADIATION

Conformal radiation administered daily, M-F, to a total dose of 61.2 Gray in 34 fractions.

Also known as: EBRT, XRT, external beam radiation therapy

ascorbate, radiation, temozolomide

Ascorbic Acid DRUG

Intravenous infusions of 87.5g of ascorbate administered three times weekly during radiation. After radiation, ascorbate is administered twice weekly through the end of cycle 6 of temozolomide.

Also known as: Vitamin C, Ascorbate, Pharmacological Ascorbate, 67457-118-50

ascorbate, radiation, temozolomide

Eligibility Criteria

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

You may qualify if:

• Ability to understand and willingness to sign informed consent (power of attorney and/or legally authorized representatives cannot sign on behalf of the patient)
• 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 or biopsy
• Age ≥ 18 years
• ECOG performance status 0-2. (KPS \> 50)
• Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
• Platelets ≥ 100,000 per mm3
• Hemoglobin ≥ 8 g/dL
• Creatinine ≤ 2.0 mg
• Total bilirubin ≤ 1.5 mg/dL
• ALT ≤ 3 times the institutional upper limit of normal
• AST ≤ 3 times the institutional upper limit of normal
• Tolerate one test dose (15g) of ascorbate.
• Not pregnant.

You may not qualify if:

• Recurrent high grade glioma
• G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Patients actively receiving insulin or using a finger-stick glucometer daily for blood glucose measurements
• 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: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
• Known active concurrent malignancy, as determined by treating physicians.
• Patients who have received prior chemotherapy (including Gliadel wafers) for the current glioma.
• Prior radiation therapy to the head or neck resulting in overlap of RT fields.
• Patients receiving any other investigational agents (imaging agents are acceptable)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would result in a hospital stay or delay of treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or impact patient safety.
• Pregnant women.
• Breastfeeding women.
• Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs.

Sponsors & Collaborators

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

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (2)

• 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

• Petronek MS, Monga V, Bodeker KL, Kwofie M, Lee CY, Mapuskar KA, Stolwijk JM, Zaher A, Wagner BA, Smith MC, Vollstedt S, Brown H, Chandler ML, Lorack AC, Wulfekuhle JS, Sarkaria JN, Flynn RT, Greenlee JDW, Howard MA, Smith BJ, Jones KA, Buettner GR, Cullen JJ, St-Aubin J, Buatti JM, Magnotta VA, Spitz DR, Allen BG. Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM. Clin Cancer Res. 2024 Jan 17;30(2):283-293. doi: 10.1158/1078-0432.CCR-22-3952.

  PMID: 37773633 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Radiotherapy; Ascorbic Acid

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)

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

Study Officials

• Bryan G. Allen, MD, PhD

  Assistant Professor, Department of Radiation Oncology, The University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Radiation Oncology

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: January 22, 2015
• Study Start: March 13, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

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)