Prostate Cancer
Conditions
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.
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.
Sponsors
Banner Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Caspase-3 (CC3) activation between baseline biopsy and radical prostatectomy specimen | Baseline (pre-treatment biopsy) through radical prostatectomy, assessed up to 6 months | Measured via immunohistochemistry on prostate biopsy tissue and radical prostatectomy specimens; change assessed between pre-treatment biopsy and surgical specimen. |
| Change in Ki-67 proliferative index between baseline biopsy and radical prostatectomy specimen | Baseline through radical prostatectomy, assessed up to 6 months | Percentage of Ki-67 expression measured via immunohistochemistry; compared between pre-treatment biopsy and radical prostatectomy specimen. |
| Change in Gleason score from biopsy to prostatectomy specimen | Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months | Pathologic Gleason Score assessed using the Gleason Grading System (score range 6-10). Higher scores indicate more aggressive prostate cancer pathology. |
| Change in Decipher genomic score in prostate tumor tissue | Baseline biopsy through radical prostatectomy specimen collection, assessed up to 6 months | Decipher Genomic Classifier Score (continuous scale ranging from 0 to 1.0). Higher scores indicate greater risk of adverse oncologic outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative complications following radical prostatectomy assessed by Clavien-Dindo classification | 30 days and 90 days following radical prostatectomy | Postoperative complications graded using the Clavien-Dindo Classification System (Grade I-V). Higher grades indicate more severe postoperative complications. |
| Incidence of Grade 2 or higher adverse events as assessed by CTCAE criteria | From initiation of semaglutide through 90 days post-radical prostatectomy | Treatment-emergent adverse events graded according to CTCAE criteria; includes events occurring during semaglutide treatment and postoperative follow-up. |
| Change in body weight | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | Measured in kilograms and compared between baseline and preoperative assessment. |
| Change in body mass index (BMI) | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | BMI (kg/m²) calculated and compared between baseline and preoperative assessment. |
| Change in hemoglobin A1c (HbA1c) | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | Measured via blood testing and compared between baseline and preoperative assessment. |
| Change in c-peptide levels | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | Measured via blood testing and compared between baseline and preoperative assessment. |
| Change in high-sensitivity C-reactive protein (hsCRP) | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | Measured via blood testing and compared between baseline and preoperative assessment. |
| Change in lipid profile parameters | Baseline through preoperative assessment performed within 14 days prior to radical prostatectomy, assessed up to 6 months | Includes total cholesterol, LDL, HDL, and triglycerides measured by blood testing and compared between baseline and preoperative assessment. |
Countries
United States
Contacts
CONTACTNibu Mathew
PRINCIPAL_INVESTIGATORIssac Bowman
Banner Health
Outcome results
None listed