Clinical trial NCT06433791: Evaluation of Ascorbate-Meglumine Therapeutic for SRS
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)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Safety
Lead sponsor: LadeRx LLC
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
First posted: 2024-05-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: dose escalation
Primary purpose: TREATMENT

Brief 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)

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Safety as measured by adverse events
timeFrame: 1 week after receiving study drug with SRS
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Health
state: North Carolina
Study officials:
affiliation: Duke Health
name: John Kirkpatrick, MD
role: PRINCIPAL_INVESTIGATOR
References: