Clinical trial NCT06328686: Arginine and Whole Brain Radiation Therapy for the Treatment of Patients With Brain Metastases
Official title: Arginine With Whole Brain Radiation Therapy for the Treatment of Brain Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Metastatic Malignant Neoplasm in the Brain
Metastatic Malignant Solid Neoplasm
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-03-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak plasma L-arginine (arginine) and arginine metabolite concentration
timeFrame: Within 4 hours of oral and intravenous (IV) dosing of L-arginine
Secondary outcomes:
measure: Incidence of adverse events associated with delivering L-arginine with standard fractionation whole brain radiation therapy
timeFrame: At 1 week into radiation and at completion of 2 week course
measure: Side effect profile of oral and IV arginine
timeFrame: On days 1, 5, and 10
measure: Frontal cortex blood volume/flow changes with L-arginine administration
timeFrame: Up to 1 year
measure: Describe The Immunological Effects of Oral versus IV Arginine
timeFrame: Up to 10 days
measure: Describe The Metabolic Effects of Oral versus IV Arginine
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Hospital/Winship Cancer Institute
name: Lisa Sudmeier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: