Glioblastoma MultiformePhase 2NCT02344355
A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma Multiforme
A Phase 2 study testing Temozolomide, radiation therapy and Ascorbic Acid in people with Glioblastoma Multiforme, run by Bryan Allen at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Temozolomide, radiation therapy and Ascorbic Acid
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2017to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: Pharmacological Ascorbate Combined With Radiation and Temozolomide in Glioblastoma Multiforme: A Phase 2 Trial
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.
Read the detailed description
Standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). After radiation, patients receive additional cycles of temozolomide (adjuvant chemotherapy).
Participants will:
- receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase
- receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
- complete health-related quality of life questionnaires pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and then every 3 months. In addition, patients will complete neurocognitive testing pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and approximately 9 months after initiating radiation therapy.
The adjuvant chemotherapy portion of this study lasts for 6 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Temozolomide, radiation therapy, Ascorbic Acid
- Keywords
- Ascorbic Acid, temozolomide, radiation
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar, Temodal
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.
radiation therapyRadiation
Also called EBRT, XRT, external beam radiation therapy
Conformal radiation administered daily, M-F, to a total dose of 61.2 Gray in 34 fractions.
Ascorbic AcidDrug
Also called Vitamin C, Ascorbate, Pharmacological Ascorbate, 67457-118-50
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Temozolomide; Radiation: radiation therapy; Drug: Ascorbic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
From radiation day 1 until date of death from any cause.
Measured: monthly up to 5 years post treatment
Secondary outcomes (2)
Progression Free Survival (PFS)
From radiation day 1 to documented disease progression in MRI imaging as described by the RANO criteria
Measured: monthly up to 5 years post treatment
Adverse Event Frequency
Categorize and quantify using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4 from radiation day 1 through 7 months post-radiation.
Measured: monthly through 7 months post-radiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2015 (estimated)
- Study start13 Mar 2017
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bryan Allen
- Sponsor type
- University, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center, National Cancer Institute (NCI), Gateway for Cancer Research
- Responsible party
- Sponsor-investigator, Bryan Allen, University of Iowa
- Investigators
- Bryan G. Allen, MD, PhD, Principal investigator, Assistant Professor, Department of Radiation Oncology, The University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02344355
- Sponsor's protocol ID
- 201504786
- Status last verified
- Sep 2026
- First submitted
- 16 Jan 2015
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.
Publications
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.
PubMed 28366679Petronek 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.
PubMed 37773633
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Ascorbate Combined With Radiation and Temozolomide in Glioblastoma Multiforme: A Phase 2 Trial
- ClinicalTrials.gov ID
- NCT02344355
- Acronym / sponsor ID
- 201504786
- Conditions
- Glioblastoma Multiforme
- Keywords
- Ascorbic Acid, temozolomide, radiation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Bryan AllenUniversity, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center, National Cancer Institute (NCI), Gateway for Cancer Research
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 22 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth). After radiation, patients receive additional cycles of temozolomide (adjuvant chemotherapy).
Participants will:
- receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase
- receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy (after radiation)
- complete health-related quality of life questionnaires pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and then every 3 months. In addition, patients will complete neurocognitive testing pre-radiation, 4 weeks into radiation, 4 weeks after radiation, and approximately 9 months after initiating radiation therapy.
The adjuvant chemotherapy portion of this study lasts for 6 months. After that is completed, participants will go back to standard therapy for their cancer. Participants will continue to have life-long follow-up for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ascorbate, radiation, temozolomide | Experimental | Drug: Temozolomide, Radiation: radiation therapy, Drug: Ascorbic AcidConcomitant therapy: Radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions Adjuvant therapy: Oral temozolomide and pharmacological ascorbate (ascorbic acid) infusions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemozolomideAlso: Temodar, Temodaloral 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. | Drug | ascorbate, radiation, temozolomide |
| radiation therapyAlso: EBRT, XRT, external beam radiation therapyConformal radiation administered daily, M-F, to a total dose of 61.2 Gray in 34 fractions. | Radiation | ascorbate, radiation, temozolomide |
| Ascorbic AcidAlso: Vitamin C, Ascorbate, Pharmacological Ascorbate, 67457-118-50Intravenous 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. | Drug | ascorbate, radiation, temozolomide |
Primary outcome
Overall Survival (OS)
Time frame: monthly up to 5 years post treatment
From radiation day 1 until date of death from any cause.
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: monthly up to 5 years post treatment
Adverse Event Frequency
Time frame: monthly through 7 months post-radiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Background: PubMed 28366679Schoenfeld 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.
- Derived from this study: PubMed 37773633Petronek 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.
- Individual participant dataSharing planned: Yes. Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan G. Allen, MD, PhD principal investigator
Assistant Professor, Department of Radiation Oncology, The University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide, radiation therapy and Ascorbic Acid in people with Glioblastoma Multiforme, run by Bryan Allen at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: monthly up to 5 years post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02344355, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.