Pharmacokinetics of IA and IV Ga68-PSMA-11 Infusion

Early Phase 1CompletedNCT04976257

Ryan Kohlbrenner, MD5 enrolled

Overview

Prostate-specific membrane antigen (PSMA) agents have shown promise in detecting and treating prostate cancer. Gallium-68-labeled PSMA-11 (68Ga-PSMA-11) is a radioactive agent that binds to prostate cancer cells and can be imaged using positron emission tomography (PET) scanners that detect radioactivity in the body. This early phase I study will use PET to determine if delivering 68Ga-PSMA-11 directly into the prostatic artery (intra-arterial (IA) administration) results in greater uptake in the prostate than delivering 68Ga-PSMA-11 into a vein in the arm (intravenous (IV) administration).

PRIMARY OBJECTIVE: I. To compare the maximum standardized uptake value (SUVmax) in tumoral regions-of-interest during prostatic arterial and intravenous 68Ga-PSMA-11 infusions. SECONDARY OBJECTIVES: I. To compare the tumoral time-activity curves for selective prostatic arterial and intravenous 68Ga-PSMA-11 infusions. II. To study PSMA receptor saturation kinetics during selective prostatic arterial infusion of 68Ga-PSMA-11 (obtained only from arterial time activity curves \[TACs\] ipsilateral to the side of infusion). OUTLINE: Patients receive 68Ga-PSMA-11 IV over 30 minutes and undergo dynamic PET imaging over infusion period and for 15 minutes after on day 1. 1-14 days later, patients undergo pelvic angiogram and prostatic arterial catheterization. Patients then receive 68Ga-PSMA-11 IA over 30 minutes and undergo dynamic PET imaging over infusion period and for 15 minutes after. After completion of study, patients are followed up with 24 hours after the IA infusion and PET scan.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age greater than or equal to 18 years and less than or equal to 80 years. * Children are excluded from this study because the disease does not occur in children * Individuals from age 76 to age 80 must have a prior CT of the abdomen and pelvis within 5 years of first PSMA scan demonstrating non-occlusive pelvic atherosclerosis, regardless of smoking status * Individuals over the age of 80 are excluded from this study to improve the likelihood of a catheterizable prostatic artery, given the higher rates of occlusive atherosclerosis with advanced age * Ability to provide informed consent * Biopsy-proven unilateral or bilateral prostate adenocarcinoma, any stage (any N or any M) * Large tumor burden, characterized by either * A discrete lesion with maximal tumor diameter \>= 2.0cm on at least one affected side, documented on prostate magnetic resonance imaging (MRI) or Transrectal ultrasound (TRUS) within 4 months of first scan. * Infiltrative disease with primary pattern Gleason 4 adenocarcinoma in at least 4 of 6 sextant core biopsy locations on at least one affected side, documented in a surgical pathology report within 4 months of first scan. * Gleason score \>= 4+4 * Cancer of the Prostate Risk Assessment (CAPRA) score \>= 6 Exclusion Criteria: * Body mass index (BMI) \> 35 kg/m\^2 * Prior treatment for prostate cancer, or any use of anti-androgen therapy within 3 months of first scan * History of any pelvic radiotherapy * Severe atherosclerosis from prior CT imaging study, or greater than 10 pack-year smoking history if no prior imaging available. * Stage IV or V chronic kidney disease by estimated glomerular filtration rate (eGFR) within 45 days of first scan * Platelet count \< 50 x 10\^9/L and/or international normalized ratio \> 1.5 * Severe allergy to iodinated contrast * Active urinary tract infection or recent episode of prostatitis within 1 month of first scan * Inability to tolerate prolonged supine positioning

Outcomes

Primary Outcomes

Maximum standardized uptake value (SUVmax)

A two-sided paired t-test will determine whether the ipsilateral SUVmax values obtained during selective arterial 68Ga-PSMA-11 infusions are greater than those obtained during venous infusions. A similar paired analysis will be made during arterial infusions to compare tumoral regions of interest (ROIs) ipsilateral and contralateral to the side of the infusion. Means/medians, ranges/standard deviations will be calculated for each endpoint.