Impact of Monosodium Glutamate on 68GA-PSMA-11, PET Imaging Biodistribution in Patients With Prostate Cancer (MSG PSMA PET)

Evaluation by 68Ga-PSMA-11 PET Imaging of Monosodium Glutamate as a Potential Agent for Salivary Gland Protection Under PSMA-targeted Alpha-therapy: a Randomized Pilot Imaging Research Study

This phase I trial studies the impact of monosodium glutamate (MSG) on 68GA-PSMA-11 PET/CT in decreasing the salivary glands uptake in patients with prostate cancer. Prostate specific membrane antigen (PSMA) is a molecule that is overexpressed by the prostate cancer cells. 68GA-PSMA-11 is an imaging radioactive drug that can target this molecule in tissues for imaging and therapy of prostate cancer. Food substances, such as monosodium glutamate, may reduce salivary gland uptake of 68GA-PSMA-11. Ultimately, giving MSG may reduce potential harm and injury to the salivary glands in patients with prostate cancer treated with PSMA-targeted molecular radiotherapy.

Study Overview

• Status: Completed
• Conditions: Prostate Carcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Gallium Ga 68-labeled PSMA-11; Procedure: Biospecimen Collection; Dietary supplement: Monosodium Glutamate

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effect of monosodium glutamate (MSG) administration (glutamate supplementation) on the salivary gland uptake of gallium Ga 68-labeled PSMA-11 (68Ga-PSMA-11).

SECONDARY OBJECTIVES:

I. To determine the effect of MSG administration on renal 68Ga-PSMA-11 uptake. II. To determine the effect of MSG administration on tumor 68Ga-PSMA-11 uptake. III. To determine if 68GA-PSMA-11 is excreted in the saliva. IV. Safety of MSG administration both oral ingestion and oral-salivary stimulation.

OUTLINE: Patients are randomized to 1 of 2 arms.

Arm I: Patients receive gallium Ga 68-labeled PSMA-11 intravenously (IV) and undergo a positron emission tomography (PET)/computed tomography (CT) scan on day 1. Within 2 weeks (days 2-14), patients receive MSG orally (PO) over 10 minutes and receive a second dose of gallium Ga 68-labeled PSMA-11 IV, followed by a second PET/CT scan. Patients also undergo collection of saliva at 0, 30, and 60 minutes after gallium Ga 68-labeled PSMA-11 injection and 90 minutes after PET/CT.

Arm II: Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo a PET/CT scan on day 1. Within 2 weeks (days 2-14), patients receive a second dose of gallium Ga 68-labeled PSMA-11 IV immediately followed by MSG applied in the mouth over 30 seconds every 10 minutes for a total of 6 times, and then undergo a second PET/CT scan. Patients also undergo collection of saliva at 0, 30, and 60 minutes after gallium Ga 68-labeled PSMA-11 injection and 90 minutes after PET/CT.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patient volunteer to undergo 2 PSMA PET/CT scans within 14 days
• Histopathologically proven prostate cancer (PCa)

• PSMA PET/CT indicated for :

  • Initial staging before definitive therapy
  • Biochemical recurrence localization
  • Metastatic disease re-staging
• Ability to understand a written informed consent document and the willingness to sign it
• Ability to ingest 300 mL of fluid across 10 minute period

Exclusion Criteria:

• Prior salivary gland surgery or radiation therapy
• Prior history or current salivary gland disease
• Unable to lie flat, still or tolerate a PET scan
• Unable to follow the salivary flow stimuli administration regimen
• Unable to follow the glutamate supplementation administration regimens
• Asthma
• Severe uncontrolled hypertension (systolic blood pressure above 140 mm Hg and diastolic blood pressure above 90 mm Hg, or systolic blood pressure above 180 mm Hg, or diastolic blood pressure above 110 mg Hg). Patients with controlled hypertension under medication are eligible
• Sodium/salt restricted diet due to other medical conditions
• History of severe asthma that has led to hospitalizations or emergency room visits
• History of severe contraindications to MSG consumption including severe headaches, migraines or other intolerance
• Change to treatment administered between time of baseline scan and MSG scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (68GA-PSMA-11, PET/CT, monosodium glutamate); 8 patients receive gallium Ga 68-labeled PSMA-11 IV and PET/CT scan on day 1. Within 2 weeks (days 2-14), patients receive MSG PO over 10 minutes and receive a second dose of gallium Ga 68-labeled PSMA-11 IV, followed by a second PET/CT scan. Patients also undergo collection of saliva at 0, 30, and 60 minutes after gallium Ga 68-labeled PSMA-11 injection and 90 minutes after PET/CT.	Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; tomography; computerized tomography; CT scan; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; positron emission tomography scan; Drug: Gallium Ga 68-labeled PSMA-11; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; Gallium Ga 68 PSMA-11; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; Procedure: Biospecimen Collection; Undergo collection of saliva; Dietary supplement: Monosodium Glutamate; Given PO; Other Names: MSG Monohydrate; Sodium Glutamate Monohydrate
EXPERIMENTAL: Arm II (68GA-PSMA-11, PET/CT, monosodium glutamate); 8 patients receive gallium Ga 68-labeled PSMA-11 IV and undergo a PET/CT scan on day 1. Within 2 weeks (days 2-14), patients receive a second dose of gallium Ga 68-labeled PSMA-11 IV immediately followed by MSG applied in the mouth over 30 seconds every 10 minutes for a total of 6 times, and then undergo a second PET/CT scan. Patients also undergo collection of saliva at 0, 30, and 60 minutes after gallium Ga 68-labeled PSMA-11 injection and 90 minutes after PET/CT.	Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; tomography; computerized tomography; CT scan; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; positron emission tomography scan; Drug: Gallium Ga 68-labeled PSMA-11; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; Gallium Ga 68 PSMA-11; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; Procedure: Biospecimen Collection; Undergo collection of saliva; Dietary supplement: Monosodium Glutamate; Given PO; Other Names: MSG Monohydrate; Sodium Glutamate Monohydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary gland uptake of gallium Ga 68-labeled PSMA-11 (68Ga-PSMA-11)	Standard uptakes values (SUV) values (maximum SUV [SUVmax] and SUVmean) in all assessable salivary glands will be measured with a spherical volume-of-interest with and without the administration of monosodium glutamate (MSG) interventions. SUVmax/salivary gland will be calculated and a mean SUVmax/patient will be generated. The aim is to show a 2-fold reduction of the salivary gland 68Ga-PSMA-11 uptake after MSG administration. Paired T-test will be used to determine statistical significance per salivary gland and per patient.	2 measurements within 2 to 14 days maximum (on positron emission tomography [PET]1 and PET2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal 68Ga-PSMA-11 uptake	SUVmax and SUVmean in the kidneys will be measured with a spherical volume-of-interest with and without the administration of MSG interventions. SUVmax/kidneys will be calculated and a mean SUVmax/patient will be generated. Paired T-test will be used to determine statistical significance per salivary gland and per patient.	2 measurements within 2 to 14 days maximum (on PET1 and PET2)
Tumor 68Ga-PSMA-11 uptake	SUVmax and SUVmean in the visible tumor lesions will be measured with a spherical volume-of-interest with and without the administration of MSG interventions. SUVmax/tumor lesions will be calculated and a mean SUVmax/patient will be generated. Paired T-test will be used to determine statistical significance per salivary gland and per patient.	2 measurements within 2 to 14 days maximum (on PET1 and PET2)
Saliva radioactivity concentration	Saliva radioactivity concentration will be compared with and without saliva stimuli.	2 measurements within 2 to 14 days maximum (on PET1 and PET2)
Incidence of adverse events of MSG administration		Up to 6 months

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Investigators: Principal Investigator: Jeremie Calais, M.D., UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 5, 2019
• Primary Completion (ACTUAL): May 6, 2020
• Study Completion (ACTUAL): May 6, 2020

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Edetic Acid; Gallium 68 PSMA-11
• Other Study ID Numbers: 18-001776 (OTHER: UCLA / Jonsson Comprehensive Cancer Center); NCI-2019-04437 (REGISTRY: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No