Metastatic Malignant Neoplasm in the BrainEarly Phase 1NCT06328686
Arginine and Whole Brain Radiation Therapy for the Treatment of Patients With Brain Metastases
A Early Phase 1 study testing Arginine, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Neoplasm in the Brain and Metastatic Malignant Solid Neoplasm, run by Emory University at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm
- What is being tested?
- Arginine, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Sep 2024to 31 Dec 2028
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Adult not able to consent for self
- Pregnant
- Prisoners
- Cognitively impaired/impaired decision-making capacity
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Lisa Sudmeier, MD, PhD, 404-712-9625, lsudmei@emory.edu
Agnes Harutyunyan, aharuty@emory.edu
About this study
Official title: Arginine With Whole Brain Radiation Therapy for the Treatment of 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.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the bioavailability of orally-administered arginine (L-arginine).
SECONDARY OBJECTIVES:
- 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.
- Being tested
- Arginine, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Spectroscopy
- Medical subject headings
- Brain Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArginineDrug
Also called Amino-5-guanidino-pentanoic acid, Arg, L-Arginine
Given IV or PO
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Undergo MRI
SpectroscopyProcedure or surgery
Undergo spectroscopy
Whole-Brain RadiotherapyRadiation
Also called WBRT, whole-brain radiation therapy
Undergo WBRT
| Study group | Role | What they receive |
|---|---|---|
| Arm A (IV L-arginine, WBRT) | Experimental | 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. Receives: Drug: Arginine; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Spectroscopy; Radiation: Whole-Brain Radiotherapy |
| Arm B (oral L-arginine, WBRT) | Experimental | 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. Receives: Drug: Arginine; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Spectroscopy; Radiation: Whole-Brain Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 4 hours of oral and intravenous (IV) dosing of L-arginine
Secondary outcomes (5)
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.
Measured: At 1 week into radiation and at completion of 2 week course
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.
Measured: On days 1, 5, and 10
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.
Measured: Up to 1 year
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.
Measured: Up to 10 days
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.
Measured: Up to 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2024
- Study start5 Sep 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Malignant Neoplasm in the BrainStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Lisa Sudmeier, Emory University
- Investigators
- Lisa Sudmeier, MD, PhD, Principal investigator, Emory University Hospital/Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06328686
- Sponsor's protocol ID
- STUDY00005787
- Other IDs
- NCI-2023-10895, STUDY00005787, WINSHIP5883-23, P30CA138292
- Status last verified
- Sep 2026
- First submitted
- 19 Feb 2024
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No