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

90 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Temozolomide for treating glioblastoma?

Research shows that Temozolomide, when used with radiotherapy, improves survival in patients with glioblastoma. It has been effective in treating various brain tumors, including newly diagnosed glioma and recurrent malignant glioma. ^{1 2 3 4 5}

Is high-dose vitamin C with radiation therapy safe for humans?

Intensity-modulated radiation therapy (IMRT) is generally safe and can reduce side effects compared to older methods, but it may still expose healthy tissue to low-dose radiation, which can lead to late adverse effects like secondary cancers. ^{6 7 8 9 10}

How is the treatment of high-dose vitamin C with radiation therapy and temozolomide for glioblastoma different from other treatments?

This treatment is unique because it combines high-dose vitamin C with standard radiation therapy and temozolomide, which is not a common combination for glioblastoma. High-dose vitamin C is being explored for its potential to enhance the effects of radiation and chemotherapy, offering a novel approach compared to the standard use of temozolomide and radiation alone. ^{1 2 11 12 13}

What is the purpose of this 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.

Research Team

Bryan G. Allen, MD, PhD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. England 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. [2018]

2. Switzerland 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). [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

[Temozolomide: Temodal]. [2018]

6. India pubmed.ncbi.nlm.nih.gov

A randomized study for dosimetric assessment and clinical impact of bone marrow sparing intensity-modulated radiation therapy versus 3-dimensional conformal radiation therapy on hematological and gastrointestinal toxicities in cervical cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy, not 3 dimensional conformal, is the preferred technique for treating locally advanced disease with high-dose radiotherapy: the argument against. [2015]

9. Germany 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. [2021]

10. England 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. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients. [2023]

12. India pubmed.ncbi.nlm.nih.gov

Prognostic factors effective on survival of patients with glioblastoma: Anadolu Medical Center experience. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. [2018]