Evaluation of Ascorbate-Meglumine Therapeutic for SRS

Официальное название

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)

Обзор

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)

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Safety as measured by adverse events [Срок оценки: 1 week after receiving study drug with SRS]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Duke Health — Durham

Идентификаторы

NCT: NCT06433791 · LadeRX

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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