Evaluation of Ascorbate-Meglumine Therapeutic for SRS

Safety Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06433791
• Other study ID #: LadeRX
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 17, 2024
• Est. completion date: June 17, 2025

Study information

• Verified date: May 2024
• Source: LadeRx LLC
• Contact: Christopher Lascola, MD
• Phone: 9194752607
• Email: christopher.lascola[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

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.

Other known NCT identifiers

• NCT03927625

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: June 17, 2025
• Est. primary completion date: March 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Safety

Intervention

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

Locations

Country	Name	City	State
United States	Duke Health	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
LadeRx LLC	Duke Clinical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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