Preoperative Semaglutide Prior to Radical Prostatectomy

NCT07727473 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 2241-2114
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

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

Secondary Outcomes (8)

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

  30 days and 90 days following radical prostatectomy

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

  From initiation of semaglutide through 90 days post-radical prostatectomy

• Change in body weight

  Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months

• Change in body mass index (BMI)

  Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months

• Change in hemoglobin A1c (HbA1c)

  Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months

Study Arms (1)

Semaglutide Preoperative Treatment

EXPERIMENTAL

Participants enrolled in this single-arm study will receive weekly subcutaneous semaglutide for 3 to 6 months prior to planned radical prostatectomy. Semaglutide will be administered according to the FDA-approved dosing regimen, with dose titration as tolerated. Treatment will be discontinued one week prior to surgery, after which participants will proceed with standard-of-care radical prostatectomy and postoperative follow-up.

Drug: Semaglutide 2.4 mg

Interventions

Semaglutide 2.4 mg DRUG

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.

Semaglutide Preoperative Treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Banner Health: lead

Study Sites (1)

Banner MD Anderson Cancer Center at Gateway

Gilbert, Arizona, 85234, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Issac Bowman

  Banner Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nibu Mathew

CONTACT

480-256-3425; nibu.mathew@bannerhealth.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: July 27, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)