MeFAMP for Imaging System A Amino Acid Transport in Primary and Metastatic Brain Tumors

Study Overview
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Brief Summary
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This first-in-human study will establish the human safety and radiation dosimetry of the system A amino acid transport substrate, (R)-3-[F-18]fluoro-2-methyl-2-(methylamino)propanoic acid ([F-18]MeFAMP), for positron emission tomography (PET) imaging of primary and metastatic brain tumors. This study will include 3 cohorts: healthy volunteers for whole body dosimetry estimates (n=6-8, Dosimetry Cohort), patients undergoing evaluation for recurrent high grade glioma after radiation therapy (n=10, high grade glioma (HGG) Cohort), and patients with brain metastases from extra-cranial solid tumors before and after radiation therapy (n=10, Metastasis Cohort). Exploratory assessment of the diagnostic accuracy of MeFAMP for distinguishing recurrent/progressive brain tumors from radiation-related treatment effects will also be performed for subsequent trial design. The study will complete accrual and safety assessment in the Dosimetry Cohort before recruiting for the HGG and Metastasis Cohorts.

Official Title
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MeFAMP for Imaging System A Amino Acid Transport in Primary and Metastatic Brain Tumors

Conditions
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Healthy Volunteers, Recurrent Glioma, Brain Metastases From Extra-cranial Solid Tumors

Intervention / Treatment
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* Drug: [F-18]MeFAMP PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for all cohorts: 18 years of age or older at the time of enrollment Females with childbearing potential must have a negative urine human chorionic gonadotropin (hCG) test on the day of procedure or a serum hCG test within 48 hours prior to the administration MeFAMP. Must have a life expectancy greater than 12 weeks. Exclusion Criteria for all cohorts: Use of an investigational drug for any indication within 3 months prior to the imaging study. Pregnancy or breast feeding Inability to complete the PET scans. Significant renal or hepatic dysfunction (estimated glomerular filtration rate (GFR) < 60 mL/min) Any condition which may interfere with ability to participate in or complete all study-related activities as assessed by the study team. 6.4.9.3. Inclusion criteria specific to Dosimetry Cohort Normal complete metabolic profile (CMP) and cell blood count (CBC) with differential at baseline. Normal ECG at baseline. Exclusion criteria specific to Dosimetry Cohort 1) Major medical problems (e.g. renal, hepatic, inflammatory) that could interfere with biodistribution of MeFAMP as assessed by the study team. Inclusion Criteria specific to HGG Cohort Grade III or Grade IV glioma previously treated with radiation therapy Standard of care contrast-enhanced MRI showing an enhancing lesion at least 1-cm in maximum dimension that is equivocal or suspicious for recurrent glioma. Eastern Cooperative Oncology Group (ECOG) performance score of 2 or better Inclusion Criteria specific to Metastasis Cohort At least one brain metastasis from melanoma, lung cancer (small or non-small cell), or breast cancer measuring at least 1-cm in maximum dimension on contrast-enhanced MRI Plan for stereotactic radiation therapy within 2 weeks of initial MeFAMP-PET/MRI scan. ECOG performance score of 2 or better Inclusion of Women and Minorities Patients 18 years of age or older will be eligible for study participation. No other discriminatory factors, including age, sex, or ethnic background will be used to determine eligibility. Every effort will be made to ensure that minorities are recruited for study participation.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers (cohort 1)<br>Whole Body Dosimetry for healthy volunteers | Drug: [F-18]MeFAMP PET<br>* Study participants will receive the fluorine-18 labeled system A amino acid transport substrate, (R)-3-[F-18]fluoro-2-methyl-2-(methylamino)propanoic acid ([F-18]MeFAMP), for positron emission tomography (PET). Participants in Cohorts 1 and 2 will receive a single administration of the study drug. Participants in cohort 3 will receive 2 administrations of the study drug, once before standard of care radiation therapy for brain metastases and once after.<br>|
| Experimental: High Grade Glioma (cohort 2)<br>Recurrent high grade glioma after radiation therapy | Drug: [F-18]MeFAMP PET<br>* Study participants will receive the fluorine-18 labeled system A amino acid transport substrate, (R)-3-[F-18]fluoro-2-methyl-2-(methylamino)propanoic acid ([F-18]MeFAMP), for positron emission tomography (PET). Participants in Cohorts 1 and 2 will receive a single administration of the study drug. Participants in cohort 3 will receive 2 administrations of the study drug, once before standard of care radiation therapy for brain metastases and once after.<br>|
| Experimental: Brain Metastasis (cohort 3)<br>Brain metastases from extra-cranial solid tumors before and after radiation therapy | Drug: [F-18]MeFAMP PET<br>* Study participants will receive the fluorine-18 labeled system A amino acid transport substrate, (R)-3-[F-18]fluoro-2-methyl-2-(methylamino)propanoic acid ([F-18]MeFAMP), for positron emission tomography (PET). Participants in Cohorts 1 and 2 will receive a single administration of the study drug. Participants in cohort 3 will receive 2 administrations of the study drug, once before standard of care radiation therapy for brain metastases and once after.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human dosimetry for [F-18]MeFAMP. | The changing concentrations of radioactivity in normal organs and tissues will be measured in each participant at 3 time points after [F-18]MeFAMP injection in Cohort 1. These data will be used to estimate human dosimetry as effective dose in milliSieverts. | From injection to 45 minutes, 2 hours, and 4 hours after PET agent administration. | 
| Safety of [F-18]MeFAMP | Laboratory values including complete metabolic panel (CMP) and complete blood count with differential (CBC with diff) and adverse events will be assessed before and after [F-18]MeFAMP administration in cohort 1. Electrocardiograms (ECG) will also be performed before and after study drug administration in cohort 1 to assess for QT prolongation and changes in heart rate, rhythm, and ECG waveforms that could represent a safety signal due to the study drug. | Lab values, ECG and adverse events will be assessed on the day of the study before and after administration of [F-18]MeFAMP for cohort 1. |