Evaluation of Ascorbate-Meglumine Therapeutic for SRS

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)

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Safety
• Intervention / Treatment: Drug: Ascorbate-Meglumine

Detailed Description

Phase 1, single-center, open-label study in subjects receiving Stereotactic Radiosurgery (SRS) for brain metastases. The study will consist of 4 principal cohorts (n=3 in each cohort). Each cohort will receive an escalating dose of ascorbate-meglumine as an Magnetic Resonance Imaging (MRI)-detectable adjunctive therapeutic to SRS.

Subjects will complete a planning MRI for SRS with gadolinium- diethylenetriamine penta-acetic acid (GD-DPTA) per standard of care for SRS. Forty-eight hours after the planning MRI, the subjects will complete the study MRI with ascorbate-meglumine contrast agent. Each cohort will receive an escalating dose of ascorbate-meglumine by intravenous administration over 1 hour during the MRI. The total dose of ascorbate-meglumine will escalate from the first cohort to the next cohort in a sequential manner. During ascorbate-meglumine infusion, MRI scans will be performed to evaluate the contrast effect and PK blood draws will occur at defined time points.

Patients will return for the SRS procedure within 1 week following the planning MRI per standard of care. During SRS, subjects will receive a second dose of ascorbate-meglumine as an adjunctive therapeutic.

Patients will enter into a follow up phase within 2 weeks after the SRS procedure per standard of care.

The primary endpoint is to evaluate the safety of parenteral ascorbate-meglumine as a MRI-detectable adjunctive therapeutic to SRS.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Christopher Lascola, MD; Phone Number: 9194752607; Email: christopher.lascola@duke.edu
• Study Contact Backup: Name: Maureen Maughan, PhD; Phone Number: 9195979530; Email: maureen.maughan@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27709
      • Duke Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Primary cancer diagnosis with newly diagnosed brain metastases
• 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 largest lesion determined during the planning MRI
• Plan of care must include Stereotactic Radiosurgery (SRS)
• SRS treatment plan must be delivered as a single RT fraction
• Age 18 years and older
• Life expectancy of at least 3 months
• GPA score 0.5 or greater
• Capable of providing written informed consent to participate in the study

Exclusion Criteria:

• Primary lesion with radiosensitive histology (i.e., small cell carcinoma, germ-cell tumors, lymphoma, leukemia, and multiple myeloma)
• Metastases in the brain stem, pons or medulla or within 3 mm of the optic apparatus (such that some portion of the optic nerve or chiasm would receive a radiation dose > 10 Gy SRS in one single fraction)
• Previous whole-brain radiation (previous SRS to or resection of other brain lesions is permitted if more than 3 months prior to the date of enrollment on this protocol)
• Pregnancy
• History or manifestation of glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency
• History of oxalate kidney stones
• History of iron overload or hemochromatosis
• History of allergy to ascorbic acid
• Anuria, dehydration, serum albumin <3.0 g/dL, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated .
• Subjects who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide.
• Subjects who are on strong inducers, inhibitors or substrates of CYP within 3 days of planned administration of study ascorbate-meglumine.
• Subjects for which MRI is contra-indicated (for example a pacemaker/recent surgery with orthopedic prosthesis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ascorbate Meglumine dose 1; 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	Drug: Ascorbate-Meglumine; Ascorbate, meglumine and sodium salt made by combining 375 mM sodium ascorbate,125 mM ascorbic acid and 125 mM meglumine in sterile water for injection; Other Names: Vitamin C
Experimental: Ascorbate Meglumine dose 2; 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	Drug: Ascorbate-Meglumine; Ascorbate, meglumine and sodium salt made by combining 375 mM sodium ascorbate,125 mM ascorbic acid and 125 mM meglumine in sterile water for injection; Other Names: Vitamin C
Experimental: Ascorbate Meglumine dose 3; 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	Drug: Ascorbate-Meglumine; Ascorbate, meglumine and sodium salt made by combining 375 mM sodium ascorbate,125 mM ascorbic acid and 125 mM meglumine in sterile water for injection; Other Names: Vitamin C
Experimental: Ascorbate Meglumine dose 4; 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	Drug: Ascorbate-Meglumine; Ascorbate, meglumine and sodium salt made by combining 375 mM sodium ascorbate,125 mM ascorbic acid and 125 mM meglumine in sterile water for injection; Other Names: Vitamin C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as measured by adverse events	Adverse events will be monitored in patients receiving ascorbate-meglumine during Stereotactic Radiosurgery (SRS)	1 week after receiving study drug with SRS

Collaborators and Investigators

• Sponsor: LadeRx LLC
• Collaborators: Duke Clinical Research Institute
• Investigators: Principal Investigator: John Kirkpatrick, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Estimated): June 17, 2024
• Primary Completion (Estimated): March 17, 2025
• Study Completion (Estimated): June 17, 2025

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 27, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: LadeRX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No