Ascorbate-Meglumine for Safety

Overseen By Maureen Maughan, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: LadeRx LLC

Must not be taking: Flecainide, methadone, amphetamines, others

Disqualifiers: Pregnancy, G6PD deficiency, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ascorbate-Meglumine, a potential supportive therapy, to determine its safety for individuals undergoing Stereotactic Radiosurgery (SRS) for brain tumors that have spread from other parts of the body. The goal is to find the right dose and understand how the treatment works when combined with MRI-guided surgery. This trial may suit those diagnosed with brain metastases from another cancer and planning to undergo SRS treatment. Participants will receive varying doses to identify the safest and most effective amount. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically flecainide, methadone, amphetamines, quinidine, and chlorpropamide, if you cannot switch to a different drug. Also, you must not be on strong inducers, inhibitors, or substrates of CYP within 3 days of the study treatment.

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

A previous study tested ascorbate-meglumine for safety in patients with cancer that had spread to the brain. The study found that ascorbate-meglumine was generally well-tolerated, indicating safety for most people. Few serious side effects occurred, and most were mild, such as tiredness and nausea. These results suggest that ascorbate-meglumine is safe enough for further study. Since this trial is in the early stages (Phase 1), it primarily focuses on testing different doses to ensure the treatment's safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for brain metastases, which often include surgery, radiation therapy, and chemotherapy, Ascorbate-Meglumine introduces a novel approach by incorporating high-dose vitamin C (ascorbate) combined with meglumine as a potential therapeutic agent. Researchers are excited about this treatment because it leverages ascorbate's potential to selectively target cancer cells while sparing healthy ones, potentially enhancing the effectiveness of stereotactic radiosurgery (SRS). Additionally, the administration of Ascorbate-Meglumine at varying dose rates aims to optimize delivery and maximize therapeutic effects, offering a fresh perspective on managing brain metastases.

What evidence suggests that Ascorbate-Meglumine might be an effective treatment for brain metastases?

Research has shown that ascorbate-meglumine, when combined with a specific radiation treatment called stereotactic radiosurgery (SRS), might help treat cancer that has spread to the brain. In this trial, participants will receive varying doses of ascorbate-meglumine to assess its safety and effectiveness. Studies have found that ascorbate-meglumine can increase cancer cells' sensitivity to radiation, potentially enhancing tumor targeting while safeguarding healthy brain tissue. Early results suggest this combination could improve outcomes for patients with brain metastases, but further research is needed to confirm these benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

John Kirkpatrick, MD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

Inclusion Criteria

GPA score 0.5 or greater

Capable of providing written informed consent to participate in the study

Life expectancy of at least 3 months

Exclusion Criteria

Pregnancy

I am taking medication that cannot be changed, such as flecainide or methadone.

I cannot have an MRI due to a pacemaker or recent surgery with metal implants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Planning MRI

Participants complete a planning MRI for SRS with gadolinium-DPTA per standard of care

1 week

1 visit (in-person)

Study MRI and Treatment

Participants receive an escalating dose of ascorbate-meglumine during MRI scans to evaluate contrast effect and PK blood draws

48 hours after planning MRI

1 visit (in-person)

Stereotactic Radiosurgery (SRS)

Participants undergo SRS procedure and receive a second dose of ascorbate-meglumine as an adjunctive therapeutic

Within 1 week after planning MRI

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbate-Meglumine

How Is the Trial Designed?

Group I: Ascorbate Meglumine dose 4 Experimental Treatment 1 Intervention

Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, includingpost-operative patients with 1-3 residual metastases. The fourth cohort of patients will receive ascorbate-meglumine at a dose administration rate of 1.25 g/min for 60 minutes. Interventions: Drug: Ascorbate-Meglumine

Group II: Ascorbate Meglumine dose 3 Experimental Treatment 1 Intervention

Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, includingpost-operative patients with 1-3 residual metastases. The third cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.63 g/min for 60 minutes. Interventions: Drug: Ascorbate-Meglumine

Group III: Ascorbate Meglumine dose 2 Experimental Treatment 1 Intervention

Patients receiving SRS treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced MRI scan showing 1-3 brain metastases, including post-operative patients with 1-3 residual metastases.The second cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.31 g/min for 60 minutes. Interventions: Drug: Ascorbate-Meglumine

Group IV: Ascorbate Meglumine dose 1 Experimental Treatment 1 Intervention

Patients receiving Stereotactic Radiosurgery (SRS) treatment for cancer metastatic to the brain from an extracranial primary site with a contrast-enhanced Magnetic Resonance Imaging (MR) scan showing 1-3 brain metastases, including post-operative patients with 1-3 residual metastases. The first cohort of patients will receive ascorbate-meglumine at a dose administration rate of 0.16 g/min for 60 minutes. Interventions: Drug: Ascorbate-Meglumine

Who Is Running the Clinical Trial?

LadeRx LLC

Lead Sponsor

Trials

1

Recruited

10+

Duke Clinical Research Institute

Collaborator

Trials

69

Recruited

242,000+

Published Research Related to This Trial

Intravenous administration of ascorbate (vitamin C) can achieve much higher plasma concentrations compared to oral intake, which is limited by absorption and excretion processes.

High concentrations of ascorbate have shown potential cell toxicity in laboratory studies, suggesting that the method of administration may significantly impact its effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbate induces autophagy in pancreatic cancer. Cullen, JJ.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03927625

Evaluation of Ascorbate-Meglumine Therapeutic for SRS Diagnostic MRI demonstrates the presence of 1 to 3 intact (not previously irradiated or resected) brain metastases. Maximum tumor diameter ≤ 2.5 cm for the ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2024-07499

Evaluation of Ascorbate-Meglumine Therapeutic for SRS Primary cancer diagnosis with newly diagnosed brain metastases; Diagnostic MRI demonstrates the presence of 1 to 3 intact (not previously irradiated or ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK571233/

List of Excluded Studies - Radiation Therapy for Brain ... - NCBI 1. Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission. Cochrane Database Syst Rev. 2000(4):Cd002805 ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT366152

Safety and efficacy evaluation of ACT001 and WBRT ... Safety and efficacy data from 45 cancer patients with brain metastasis in a phase 1b/2a study were presented. Methods: Eligible patients with SCLC, NSCLC ...

5. jtultrasound.biomedcentral.com jtultrasound.biomedcentral.com/articles/10.1186/s40349-016-0079-2

International Society for Therapeutic Ultrasound ... The data collected suggests cavitation levels that can be applied while keeping lesioning effect to the confined area and avoiding haemorrhages ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/condition/496/brain-metastases?activelyRecruiting=false&page=42

Brain Metastases Clinical Research Trials Drug efficacy and safety data will be collected. Phase. 2. Span. 270 weeks ... A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases ...

7. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/brain-metastases

Brain Metastases Clinical Trials This clinical trial evaluates the safety and feasibility of tumor treating fields (TTF) in the treatment of spinal leptomeningeal disease in patients with ...