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NCT Number: NCT06328686

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

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.

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Key information

Conditions

Metastatic Malignant Neoplasm in the Brain Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Metastatic Malignant Solid Neoplasm Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Nervous System Diseases Nervous System Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location status: Recruiting

Location contact

Agnes Harutyunyan

CONTACT

[email protected]

Lisa Sudmeier, MD, PhD

CONTACT

[email protected]

404-712-9625

Lisa Sudmeier, MD, PhD

PRINCIPAL_INVESTIGATOR

About this study

PRIMARY OBJECTIVE:

I. Determine the bioavailability of orally-administered arginine (L-arginine).

SECONDARY OBJECTIVES:

I. Test the safety of daily arginine administration with standard-fractionation whole brain radiation therapy (WBRT).

II. Determine the side effect profile of oral and intravenous (IV) L-arginine. III. Quantify frontal cortex blood volume/flow changes following L-arginine (L-arg) administration.

IV. Describe immunological effects of oral versus (vs.) IV arginine. V. Describe the metabolic effects of oral vs. IV arginine.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: 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 computed tomography (CT) at screening, undergo collection of blood samples and spectroscopy on study, and undergo magnetic resonance imaging (MRI) at screening and follow up.

ARM B: Patients receive L-arginine orally (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.

After completion of study treatment, patients are followed up at 1 month and then quarterly for 1 year.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Arginine

Dietary Supplement

Given IV or PO

Other names: Amino-5-guanidino-pentanoic acid, Arg, L-Arginine

Biospecimen Collection

Procedure

Undergo collection of blood samples

Other names: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Computed Tomography

Procedure

Undergo CT

Other names: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Magnetic Resonance Imaging

Procedure

Undergo MRI

Other names: 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

spectroscopy

Procedure

Undergo spectroscopy

Whole-Brain Radiotherapy

Radiation

Undergo WBRT

Other names: WBRT, whole-brain radiation therapy

Primary outcomes

  1. Peak plasma L-arginine (arginine) and arginine metabolite concentration

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

    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.

Secondary outcomes

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

    Time frame: At 1 week into radiation and at completion of 2 week course

    Will be evaluated using complete metabolic panel and symptom assessment. The descriptive statistics (e.g., summary statistics for numerical measurements and frequency/percentage for categorical measurements) along with data visualization (e.g., box plot repeated by time points) will mainly be considered for all 10 patients or separated by arms. As needed, the comparison between the two arms will be carried out mainly by non-parametric tests (e.g., Wilcoxon sum-rank test, Fisher's exact test). The change before and after treatment can be tested using a paired-test (e.g., Wilcoxon signed rank test). All analyses will be explored for all 10 patients or separated by arms as appropriate.

  2. Side effect profile of oral and IV arginine

    Time frame: On days 1, 5, and 10

    Will be evaluated using symptom assessment at time of lab draw. The descriptive statistics (e.g., summary statistics for numerical measurements and frequency/percentage for categorical measurements) along with data visualization (e.g., box plot repeated by time points) will mainly be considered for all 10 patients or separated by arms. As needed, the comparison between the two arms will be carried out mainly by non-parametric tests (e.g., Wilcoxon sum-rank test, Fisher's exact test). The change before and after treatment can be tested using a paired-test (e.g., Wilcoxon signed rank test). All analyses will be explored for all 10 patients or separated by arms as appropriate.

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

    Time frame: Up to 1 year

    Cerebral blood flow (CBF) and oxygen utilization will be measured using diffuse optical spectroscopy and diffuse correlation spectroscopy after arginine administration.

    The descriptive statistics (e.g., summary statistics for numerical measurements and frequency/percentage for categorical measurements) along with data visualization (e.g., box plot repeated by time points) will mainly be considered for all 10 patients or separated by arms. As needed, the comparison between the two arms will be carried out mainly by non-parametric tests (e.g., Wilcoxon sum-rank test, Fisher's exact test). The change before and after treatment can be tested using a paired-test (e.g., Wilcoxon signed rank test). All analyses will be explored for all 10 patients or separated by arms as appropriate.

  4. Describe The Immunological Effects of Oral versus IV Arginine

    Time frame: Up to 10 days

    Administration of both oral and IV formulations of L-arginine will stimulate T-cell proliferation and expression of effector molecules. A phenotypic analysis of circulating immune cells will be conducted by spectral flow cytometry during treatment.

  5. Describe The Metabolic Effects of Oral versus IV Arginine

    Time frame: Up to 10 days

    Administration of both oral and IV formulations of L-arginine will stimulate T-cell proliferation and expression of effector molecules. Arginine metabolites, including ornithine, citrulline, will have a delayed increase following arginine administration. A phenotypic analysis of circulating immune cells will be conducted by spectral flow cytometry during treatment.

Study contacts

Contact information is provided by the study sponsor or research team.

Lisa Sudmeier, MD, PhD

CONTACT

[email protected]

404-778-3473

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Mar 25, 2024
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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