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

ConditionsMetastatic Malignant Neoplasm in the BrainMetastatic Malignant Solid Neoplasm
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEmory University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Arginine

    Drug

    Given IV or PO

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Spectroscopy

    Procedure/Surgery

    Undergo spectroscopy

  • Whole-Brain Radiotherapy

    Radiation

    Undergo WBRT

Treatment groups

10 Participants
are divided into 2 treatment groups
Group A: Arm A (IV L-arginine, WBRT)Experimental treatment 6 interventions
Group B: Arm B (oral L-arginine, WBRT)Experimental treatment 6 interventions

Trial outcomes

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.

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

Secondary outcomes

1

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.

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

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.

Time frame
On days 1, 5, and 10
3

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.

Time frame
Up to 1 year
4

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.

Time frame
Up to 10 days

Other outcomes

Sponsors and contacts

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Emory University

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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