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

12 Participants Needed

Trial Summary

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.

How does the drug Ascorbate-Meglumine differ from other treatments for this condition?

Ascorbate-Meglumine is unique because it involves the use of ascorbate (vitamin C) in a pharmacological form, which is administered intravenously to achieve very high plasma levels that are not possible with oral intake. This high concentration can act as a prodrug to deliver hydrogen peroxide to tumors, potentially enhancing the effects of standard cancer treatments like chemotherapy and radiation. ^{1 2 3 4 5}

What is the purpose of this trial?

Phase 1, Single-Center, Dose-Escalating, Open-Label, Safety Clinical Trial of Parenteral Ascorbate-Meglumine as a Novel Magnetic Resonance Imaging (MRI)-guided Adjunctive Therapeutic for Stereotactic Radiosurgery (SRS)

Research Team

John Kirkpatrick, MD

Principal Investigator

Duke Health

Eligibility Criteria

Inclusion Criteria

Capable of providing written informed consent to participate in the study

GPA score 0.5 or greater

Life expectancy of at least 3 months

Exclusion Criteria

Pregnancy

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

My cancer type is known to respond well to radiation therapy.

Timeline

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)

Treatment Details

Interventions

• Ascorbate-Meglumine

Participant Groups

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+

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Blood levels and bioavailability of ascorbic acid after administration of a sustained-release formulation to humans. [2013]

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

A simple and sensitive assay for ascorbate using a plate reader. [2018]

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

Assessment of the Stability of Supraphysiological Ascorbate in Human Blood: Appropriate Handling of Samples from Clinical Trials for Measurements of Pharmacological Ascorbate. [2020]

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

Ascorbate induces autophagy in pancreatic cancer. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ascorbic acid: chemistry, biology and the treatment of cancer. [2022]