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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers (cohort 1) | Experimental | Whole Body Dosimetry for healthy volunteers |
|
| High Grade Glioma (cohort 2) | Experimental | Recurrent high grade glioma after radiation therapy |
|
| Brain Metastasis (cohort 3) | Experimental | Brain metastases from extra-cranial solid tumors before and after radiation therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [F-18]MeFAMP PET | Drug | 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. |
| 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. |
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Inclusion Criteria for all cohorts:
Exclusion Criteria for all cohorts:
6.4.9.3. Inclusion criteria specific to Dosimetry Cohort
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
Inclusion Criteria specific to Metastasis Cohort
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sebastian Eady, BS | Contact | 205-934-1082 | RadiologyCRC@uabmc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jonathan McConathy, MD, PhD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB | Birmingham | Alabama | 35294 | United States |
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| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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|
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |