Preoperative Semaglutide Prior to Radical Prostatectomy

Early Phase 1Not Yet RecruitingNCT07727473

Banner Health20 enrolled

Overview

In this exploratory, single-arm, nonrandomized trial, the impact of the preoperative utilization of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) semaglutide prior to radical prostatectomy in participants with intermediate risk prostate cancer will be investigated. Semaglutide will be administered according to the FDA-approved label for chronic weight management and participants will be dosed with a weekly subcutaneous injection. The primary aim of this trial is to explore the tumor biological activity of semaglutide in these participants. The trial will also evaluate the safety and tolerability of this preoperative treatment, along with the impact on physiologic/metabolic parameters.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prostate Cancer

Interventions

Semaglutide will be administered as a weekly subcutaneous injection. The dose will be titrated according to the FDA-approved labeling, starting at 0.25 mg once weekly and increasing as tolerated to a target maintenance dose of up to 2.4 mg once weekly. Treatment will continue for 3 to 6 months prior to planned radical prostatectomy.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male participants aged ≥18 years * Biopsy-proven intermediate-risk localized prostate cancer per NCCN risk stratification criteria * Planning to undergo radical prostatectomy, and surgical delay of 3-6 months is deemed appropriate by the investigator * Body mass index (BMI) \>35 kg/m² * No prior exposure to androgen deprivation therapy or androgen receptor pathway inhibitors Exclusion Criteria: * Prostate cancer risk classification other than intermediate risk * Hemoglobin A1c (HbA1c) \>9% * Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) * Baseline gastroparesis, dysphagia, or other significant gastrointestinal disease limiting oral intake * Current or recent (within 12 months) exposure to GLP-1 receptor agonist therapy * Delay of radical prostatectomy by 3-6 months is not deemed advisable by the investigator

Outcomes

Primary Outcomes

Change in Caspase-3 (CC3) activation between baseline biopsy and radical prostatectomy specimen

Measured via immunohistochemistry on prostate biopsy tissue and radical prostatectomy specimens; change assessed between pre-treatment biopsy and surgical specimen.

Time frame: Baseline (pre-treatment biopsy) through radical prostatectomy, assessed up to 6 months

Change in Ki-67 proliferative index between baseline biopsy and radical prostatectomy specimen

Percentage of Ki-67 expression measured via immunohistochemistry; compared between pre-treatment biopsy and radical prostatectomy specimen.

Time frame: Baseline through radical prostatectomy, assessed up to 6 months

Change in Gleason score from biopsy to prostatectomy specimen

Pathologic Gleason Score assessed using the Gleason Grading System (score range 6-10). Higher scores indicate more aggressive prostate cancer pathology.

Time frame: Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months

Change in Decipher genomic score in prostate tumor tissue

Decipher Genomic Classifier Score (continuous scale ranging from 0 to 1.0). Higher scores indicate greater risk of adverse oncologic outcomes.

Time frame: Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months

Secondary Outcomes

Incidence of postoperative complications following radical prostatectomy assessed by Clavien-Dindo classification

Postoperative complications graded using the Clavien-Dindo Classification System (Grade I-V). Higher grades indicate more severe postoperative complications.

Time frame: 30 days and 90 days following radical prostatectomy

Incidence of Grade 2 or higher adverse events as assessed by CTCAE criteria

Treatment-emergent adverse events graded according to CTCAE criteria; includes events occurring during semaglutide treatment and postoperative follow-up.

Time frame: From initiation of semaglutide through 90 days post-radical prostatectomy

Change in body weight

Measured in kilograms and compared between baseline and preoperative assessment.