There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium Prostate-Specific Membrane Antigen (177Lu-PSMA) as a radioligand therapy. This single center, pilot study will compare differences in the mechanisms of actinium-225 and lutetium-177 radioligand therapies (RLT) in participants with high or very high risk localized or locoregional prostate cancer planning on undergoing a prostatectomy.
Histologically confirmed prostate adenocarcinoma.
Willing to undergo prostatectomy with or without lymph node dissection, and candidate for prostatectomy as determined by urologic oncology.
Gleason score of 4+5 disease or higher.
Pelvic nodal metastases on PSMA PET.
Has received prior prostate cancer therapy.
Has participated in a study of an investigational therapeutic product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
Dry mouth that impacts the eating of food (i. e. requiring mouthwash prior to eating).
Concurrent serious (as determined by the principal investigator) medical conditions including but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
Parallel
177 Lutetium Prostate-Specific Membrane Antigen 617
DrugGiven intravenously (IV) or intra-arterially (IA)
Actinium-225 Prostate-Specific Membrane Antigen 617
DrugGiven IV or IA
Non-investigational, Prostatectomy
Procedure/SurgeryUndergo non-investigational surgical procedure to remove prostate.
Prostate Tissue Collection
Procedure/SurgeryWhole prostate tissue will be collected for correlative research at time of prostatectomy.
Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)
Procedure/SurgeryImaging procedure
Blood Sample Collection
Procedure/SurgeryBlood samples will be obtained for research purposes
Mean of tumor absorbed dose (Cohorts 1 and 2)
The mean tumor absorbed dose on post-treatment SPECT imaging within 7 days of the first radioligand treatment (RLT) will be obtained by using MIM Software to measure absorbed dose and researchers will manually segment activity in the dominant prostate tumor while carefully excluding any activity within the bladder using a threshold of 5 Gray. Using this segmented volume, the mean dose within the tumor in Gray for each participant and standard deviation will be calculated and reported descriptively for Cohorts 1 and 2. A two-sample t-test comparing the dose between Cohort 1 and Cohort 2 and Analysis of Variance (ANOVA) model to compare the dose between different treatment/fractionation modalities within each cohort will be performed.
Rate of Cluster of differentiation 3 positive (CD3+) T cell infiltration
Immunohistochemistry will be performed using standard methods, and stained slides will be scanned using an automated microscope scanner. Five randomly selected fields (0.25 mm\^2) from each participant's primary tumor will be captured. Using color-specific algorithms, CD3+ cell counts will be determined, and the mean of each of the five quantified fields will be used. We will use a two-sample t-test or ANOVA model comparing the CD3+ cell counts between Cohort 1 and Cohort 2 with participants who have not undergone prostatectomy enrolled in the biospecimen protocol, respectively.
Proportion of participants with reported treatment-emergent adverse events (Cohorts 1 and 2)
The proportion of participants with treatment-emergent adverse events, as classified by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5.0) will be reported for participants receiving RLT.
Proportion of participants with perioperative complications
The Clavien-Dindo classification is a widely used system for grading and classifying surgical complications. The Proportion of participants with documented perioperative complications following prostatectomy per the Clavien-Dindo classification will be reported.
Median scores on the xerostomia-quality-of-life-scale (XeQoLS)
The XeQoLS questionnaire measures the effects of salivary gland dysfunction and xerostomia on the four major domains of oral health-related quality of life: physical, pain, personal, and social. The questionnaire consists of 15 items, each rated on a 0-to-4 point Likert scale, with higher scores indicating more severe symptom burden. Median scores for each domain and global score and interquartile ranges will be reported.
Proportion of participants with 50% decrease in level of prostate specific antigen (PSA50)
The proportion of participants who achieve a greater than 50% decline from baseline PSA drawn prior to Cycle 1 Day 1 (C1D1), up to the day of prostatectomy, will be descriptively reported along with 95% binomial confidence interval. It will be compared between the two treatment Cohorts using a Fischer's test.
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Thomas Hope
Lead sponsor
University of California, San Francisco
Sponsor institution
Novartis
Collaborator
