High-Dose Vitamin C for Glioblastoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bryan Allen

Must not be taking: Warfarin, Flecainide, Methadone, others

Disqualifiers: Recurrent glioma, G6PD deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding high-dose vitamin C to the usual treatment can benefit people with glioblastoma, an aggressive brain tumor. Participants will receive radiation therapy and the chemotherapy drug temozolomide, along with vitamin C infusions. The goal is to determine if vitamin C can enhance treatment outcomes for this condition. Individuals recently diagnosed with glioblastoma who have not yet started treatment might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide, if you cannot switch to a different drug. If you are on these medications and cannot change them, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high doses of vitamin C are usually safe for people. In earlier studies, patients with glioblastoma, a type of brain cancer, received high doses of vitamin C alongside their regular treatments. These studies did not identify any major safety issues. Additionally, when tested on human glioblastoma cells in the lab, high-dose vitamin C demonstrated strong effects against tumors without harming normal cells.

This clinical trial is in phase 2, indicating that some initial safety and effectiveness have been observed in earlier stages. However, like any treatment, risks may still exist, so participants should discuss any concerns with their doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Most treatments for glioblastoma, like radiation therapy and temozolomide, are designed to attack cancer cells directly. But this new approach uses high-dose vitamin C (pharmacological ascorbate) along with these standard therapies. Researchers are excited because vitamin C at high doses may create a pro-oxidative environment that weakens cancer cells, making them more vulnerable to treatment. This could potentially enhance the effectiveness of existing treatments and offer a new way to combat this aggressive brain cancer.

What evidence suggests that high-dose vitamin C could be an effective treatment for glioblastoma?

Research has shown that high-dose vitamin C might help fight glioblastoma, a type of brain tumor. In lab studies, high-dose vitamin C effectively killed glioblastoma cells. Another study found that, when combined with chemotherapy, high-dose vitamin C helped shrink tumors in most patients. In this trial, participants will receive a combination of radiation therapy, oral temozolomide, and pharmacological ascorbate (ascorbic acid) infusions. Some reports suggest that vitamin C administered through an IV could support managing glioblastoma. While research continues, these findings offer hope that high-dose vitamin C could complement standard cancer treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Bryan G. Allen, MD, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

Adults with newly diagnosed glioblastoma multiforme who can start treatment within 5 weeks of diagnosis, have adequate organ function and blood counts, are not pregnant or breastfeeding, do not have certain other health conditions or take specific drugs that could interfere with the study.

Inclusion Criteria

Hemoglobin ≥ 8 g/dL

I can understand and am willing to sign the informed consent myself.

Absolute neutrophil count (ANC) ≥ 1500 cells per mm3

Exclusion Criteria

I use insulin or a daily finger-stick glucometer for my diabetes.

My brain tumor has come back and is aggressive.

I am taking medication that cannot be replaced, such as warfarin or methadone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Chemotherapy

Participants receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase

6-7 weeks

3 visits per week (in-person)

Adjuvant Chemotherapy

Participants receive high doses of intravenous (IV) ascorbate twice a week during adjuvant chemotherapy

6 months

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Monthly visits, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbic Acid
• Radiation Therapy
• Temozolomide

Trial Overview The trial is testing high-dose ascorbate (vitamin C) combined with standard care including Temozolomide and radiation therapy for treating brain tumors. All participants will receive this combination to see if it improves outcomes.

How Is the Trial Designed?

Group I: ascorbate, radiation, temozolomide Experimental Treatment 3 Interventions

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

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Bryan Allen

Lead Sponsor

Trials

4

Recruited

130+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

Published Research Related to This Trial

In a study of 67 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide, thalidomide, and radiation therapy resulted in a median survival of 73 weeks, indicating a favorable outcome compared to those not receiving adjuvant chemotherapy.

The treatment was generally well tolerated, but the specific benefit of adding thalidomide to temozolomide remains uncertain, as the survival outcomes were similar to those seen with other chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. Chang, SM., Lamborn, KR., Malec, M., et al.[2018]

In a Phase I clinical trial involving 37 patients with resected glioblastoma multiforme (GBM), the maximum tolerated dose (MTD) of volumetric modulated arc radiotherapy (VMAT-SIB) combined with standard dose temozolomide (TMZ) was determined to be 80 Gy delivered in 25 fractions over 5 weeks.

The trial identified dose-limiting toxicities at higher doses (82.5 Gy), with 29.7% of patients experiencing mild acute neurological toxicity and 8.1% experiencing severe toxicity, indicating that while the treatment can escalate doses, careful monitoring for side effects is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2). Ferro, M., Ferro, M., Macchia, G., et al.[2022]

Temozolomide (TMZ) is the only anticancer drug proven to improve survival in glioblastoma when used with radiotherapy, showing high concentrations in brain tumors and cerebrospinal fluid, which enhances its effectiveness.

Molecular markers like MGMT promoter methylation can predict better responses to TMZ treatment, but side effects such as myelosuppression and nausea are common, necessitating precautions like prophylaxis against Pneumocystis carinii pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. Shinoura, N., Yamada, R., Tabei, Y., et al.[2018]

In a study comparing volumetric modulated arc therapy (VMAT) to conventional 3D conformal radiotherapy (3DCRT) in cervical cancer patients, VMAT significantly reduced late small bowel toxicity, suggesting a potential improvement in long-term patient outcomes.

However, VMAT was associated with a higher risk of acute urinary toxicity, indicating that while it may reduce certain long-term side effects, it could lead to more immediate complications, particularly in patients with low body mass index (BMI) or those experiencing significant acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conventional 3D conformal radiotherapy and volumetric modulated arc therapy for cervical cancer: Comparison of clinical results with special consideration of the influence of patient- and treatment-related parameters. Dröge, LH., von Sivers, FF., Schirmer, MA., et al.[2021]

In a randomized trial involving 144 patients with anaplastic astrocytoma (AA) and glioblastoma (GBM), neoadjuvant temozolomide (NeoTMZ) did not show a survival advantage for the overall population or for GBM patients compared to radiotherapy alone.

However, patients with AA who received NeoTMZ had a significantly longer median survival of 95.1 months compared to 35.2 months for those receiving only radiotherapy, indicating a potential benefit of NeoTMZ specifically for AA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. Malmström, A., Poulsen, HS., Grønberg, BH., et al.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a study of 53 cervical cancer patients treated with post-operative intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy, there were no acute severe toxicities (grade >3) reported, indicating a high safety profile for this treatment approach.

The 5-year overall survival rate was 85%, with low rates of late toxicity (only 3.8% experienced late grade >3 toxicities), suggesting that this combined treatment is effective and well-tolerated in managing cervical cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer. Contreras, J., Srivastava, A., Chundury, A., et al.[2021]

In a study of 573 glioblastoma multiforme patients, those treated with temozolomide alongside radiotherapy experienced significantly improved overall survival, with a median survival of 14.6 months compared to 12.1 months for those receiving radiotherapy alone.

The combination treatment was associated with some adverse effects, including thrombocytopenia and nausea, but overall, the benefits in survival rates suggest that temozolomide is an effective option for newly diagnosed glioblastoma multiforme patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Cohen, MH., Johnson, JR., Pazdur, R.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8104923/

Parenteral high-dose ascorbate - A possible approach for the ... Although it is suspected that vitamin C blood levels are low in patients with glioblastoma, no data according vitamin C deficiency, symptoms, and disease ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352304225002314

High-dose vitamin C: A promising anti-tumor agent, insight ... A phase I single-arm study found that HDVC combined with chemotherapy (gemcitabine) resulted in primary tumor shrinkage in 8 out of 9 patients, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02344355

A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma ... Study Overview. This clinical trial evaluates adding high-dose ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain ...

4. mdpi.com mdpi.com/2076-3921/13/9/1095

Analysis of High-Dose Ascorbate-Induced Cytotoxicity in ... We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6162462/

The Use of Intravenous Vitamin C as a Supportive Therapy ... 4. Conclusions. Our case report indicates that IV vitamin C may be a useful supportive therapy in the management of people with glioblastoma ...