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

Emory University

Status and phase: Enrolling; Early Phase 1

Conditions: Metastatic Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06328686

WINSHIP5883-23 (Other Identifier)

STUDY00005787 (Other Identifier)

P30CA138292 (U.S. NIH Grant/Contract)

NCI-2023-10895 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Arm A (IV L-arginine, WBRT)

Experimental group

Description:

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.

Treatment:

Procedure: Spectroscopy

Dietary Supplement: Arginine

Procedure: Magnetic Resonance Imaging

Procedure: Biospecimen Collection

Radiation: Whole-Brain Radiotherapy

Procedure: Computed Tomography

Arm B (oral L-arginine, WBRT)

Experimental group

Description:

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.

Treatment:

Procedure: Spectroscopy

Dietary Supplement: Arginine

Procedure: Magnetic Resonance Imaging

Procedure: Biospecimen Collection

Radiation: Whole-Brain Radiotherapy

Procedure: Computed Tomography