Arginine and Whole Brain Radiation Therapy for the Treatment of Patients With Brain Metastases

NCT06328686 | Recruiting Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00005787NCI-2023-10895WINSHIP5883-23P30CA138292
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial evaluates different administration techniques (oral or intravenous) for arginine and tests the safety of giving arginine with whole brain radiation therapy in patients who have cancer that has spread from where it first started (primary site) to the brain (brain metastases). Arginine is an essential amino acid. Amino acids are the molecules that join together to form proteins in the body. Arginine supplementation has been shown to improve how brain metastases respond to radiation therapy. The optimal dosing of arginine for this purpose has not been determined. This study measures the level of arginine in the blood with oral and intravenous dosing at specific time intervals before and after drug administration to determine the best dosing strategy.

Conditions

Metastatic Malignant Neoplasm in the Brain; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Peak plasma L-arginine (arginine) and arginine metabolite concentration

  By compartmental pharmacokinetic analysis, the plasma arginine levels at before administration, 10 min, 30 min, 1 hour, 2 hours, and 4 hours post administration will be used to estimate the median time to reach the peak plasma arginine and the mean value of peak. This will be done separately by two arms.

  Within 4 hours of oral and intravenous (IV) dosing of L-arginine

Secondary Outcomes (5)

• Incidence of adverse events associated with delivering L-arginine with standard fractionation whole brain radiation therapy

  At 1 week into radiation and at completion of 2 week course

• Side effect profile of oral and IV arginine

  On days 1, 5, and 10

• Frontal cortex blood volume/flow changes with L-arginine administration

  Up to 1 year

• Describe The Immunological Effects of Oral versus IV Arginine

  Up to 10 days

• Describe The Metabolic Effects of Oral versus IV Arginine

  Up to 10 days

Study Arms (2)

Arm A (IV L-arginine, WBRT)

EXPERIMENTAL

Patients receive L-arginine IV over 10-20 minutes followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.

Dietary Supplement: Arginine; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Spectroscopy; Radiation: Whole-Brain Radiotherapy

Arm B (oral L-arginine, WBRT)

EXPERIMENTAL

Patients receive L-arginine PO followed by WBRT approximately 1 hour later for up to 10 days of treatment over 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT at screening, undergo collection of blood samples and spectroscopy on study, and undergo MRI at screening and follow up.

Dietary Supplement: Arginine; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Spectroscopy; Radiation: Whole-Brain Radiotherapy

Interventions

Arginine DIETARY_SUPPLEMENT

Given IV or PO

Also known as: Amino-5-guanidino-pentanoic acid, Arg, L-Arginine

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Spectroscopy PROCEDURE

Undergo spectroscopy

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Whole-Brain Radiotherapy RADIATION

Undergo WBRT

Also known as: WBRT, whole-brain radiation therapy

Arm A (IV L-arginine, WBRT); Arm B (oral L-arginine, WBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of brain metastases from any primary cancer
• Planned to undergo whole-brain radiation therapy (Hippocampal avoidant is ok)
• No systemic anti-neoplastic agent concurrent with WBRT (memantine is ok)
• Not inpatient at the time of treatment start
• Age 18 or older
• Able to consent for self

You may not qualify if:

• Patient unwilling/unable to receive daily arginine treatment (IV or oral) for the 10 days of WBRT
• Systemic therapy continuing during WBRT
• Creatinine \> 1.5 x the upper limit of normal
• Alanine aminotransferase (ALT) \> 6x the upper limit of normal
• Patient planned to be treated as an inpatient
• Age \< 18 years
• Adult not able to consent for self
• Pregnant
• Prisoners
• Cognitively impaired/impaired decision-making capacity

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis

Interventions

Arginine; Specimen Handling; Magnetic Resonance Spectroscopy; Spectrum Analysis

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Chemistry Techniques, Analytical

Study Officials

• Lisa Sudmeier, MD, PhD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Sudmeier, MD, PhD

CONTACT

404-778-3473; lisa.jane.sudmeier@emory.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: March 25, 2024
• Study Start: September 5, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 17, 2025

Record last verified: 2025-09

Locations

US (1)