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

Metastatic Malignant Solid Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06328686
• Other study ID #: STUDY00005787
• Secondary ID: NCI-2023-10895ST
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: May 31, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Emory University
• Contact: Lisa Sudmeier, MD, PhD
• Phone: 404-778-3473
• Email: lisa.jane.sudmeier[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Malignant Solid Neoplasm
• Neoplasms

Intervention

Dietary Supplement:
• Arginine
Given IV or PO

Procedure:
• Biospecimen Collection
Undergo collection of blood samples
• Computed Tomography
Undergo CT
• Magnetic Resonance Imaging
Undergo MRI
• Spectroscopy
Undergo spectroscopy

Radiation:
• Whole-Brain Radiotherapy
Undergo WBRT

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of adverse events associated with delivering L-arginine with standard fractionation whole brain radiation therapy	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.	At 1 week into radiation and at completion of 2 week course
Secondary	Side effect profile of oral and IV arginine	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.	On days 1, 5, and 10
Secondary	Frontal cortex blood volume/flow changes with L-arginine administration	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.	Up to 1 year
Secondary	Describe The Immunological Effects of Oral versus IV Arginine	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.	Up to 10 days
Secondary	Describe The Metabolic Effects of Oral versus IV Arginine	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.	Up to 10 days