## Protocol Section
### Identification Module
**NCT ID:** NCT06433791

**Brief Title:** 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)

#### Organization Study ID Info
**ID:** LadeRX
#### Organization
**Class:** INDUSTRY
**Full Name:** LadeRx LLC
### Status Module
#### Completion Date
**Date:** 2025-06-17

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-27

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-03-17

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-17

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-27
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Duke Clinical Research Institute

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** LadeRx LLC

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Safety

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

**Intervention Model Description:** dose escalation

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 12

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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

**Intervention Names:**

- Drug: Ascorbate-Meglumine

**Label:** Ascorbate Meglumine dose 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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

**Intervention Names:**

- Drug: Ascorbate-Meglumine

**Label:** Ascorbate Meglumine dose 2

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 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

**Intervention Names:**

- Drug: Ascorbate-Meglumine

**Label:** Ascorbate Meglumine dose 3

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** 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

**Intervention Names:**

- Drug: Ascorbate-Meglumine

**Label:** Ascorbate Meglumine dose 4

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Ascorbate Meglumine dose 1

- Ascorbate Meglumine dose 2

- Ascorbate Meglumine dose 3

- Ascorbate Meglumine dose 4

**Description:** 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

**Name:** Ascorbate-Meglumine

**Other Names:**

- Vitamin C

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Adverse events will be monitored in patients receiving ascorbate-meglumine during Stereotactic Radiosurgery (SRS)

**Measure:** Safety as measured by adverse events

**Time Frame:** 1 week after receiving study drug with SRS

### Eligibility Module

**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)

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** christopher.lascola@duke.edu

**Name:** Christopher Lascola, MD

**Phone:** 9194752607

**Role:** CONTACT

**Contact 2:**

**Email:** maureen.maughan@duke.edu

**Name:** Maureen Maughan, PhD

**Phone:** 9195979530

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Durham

**Country:** United States

**Facility:** Duke Health

**State:** North Carolina

**Zip:** 27709

#### Overall Officials

**Official 1:**

**Affiliation:** Duke Health

**Name:** John Kirkpatrick, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M4513

- Name: Ascorbic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: T477

- Name: Vitamin C

- Relevance: HIGH

- As Found: SARS-CoV-2

- ID: T437

- Name: Ascorbic Acid

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
