Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

NCT04887935 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202107070
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study of the tolerability and safety of neoadjuvant dapagliflozin for patients with unfavorable intermediate, high-risk, or very high-risk prostatic adenocarcinoma prior to radical prostatectomy. The primary hypothesis is that four weeks of daily dapagliflozin prior to surgery is well-tolerated and safe to use in this patient population. The investigators also hypothesize that dapagliflozin will be efficacious in resulting in tumor shrinkage on pre-operative imaging and will result in tumor necrosis at prostatectomy.

Conditions

Prostate Cancer; Cancer of Prostate

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of toxicities related to dapagliflozin as measured by CTCAE v 5.0

  From cycle 1 day 1 (the cycle is 28 days in length) through 30 days after prostatectomy (approximately day 64)

• Proportion of patients who are able to successfully complete at least 80% of the planned dapagliflozin doses and undergo radical prostatectomy

  The study will be feasible if at least 19 of the 24 enrolled subjects are able to complete at least 80% of the planned dapagliflozin doses and undergo radical prostatectomy as scheduled.

  At approximately 6 weeks

Secondary Outcomes (6)

• MRI quantified change in tumor size from screening to post-treatment

  At the time of pre-operative prostate MRI (estimated to be at week 6)

• Degree of tumor necrosis/shrinking

  From screening to time of radical prostatectomy (estimated to be at week 6)

• Change in plasma glucose

  From screening to day 29

• Change in C-peptide

  From screening to day 29

• Change in HbA1C

  From screening to day 29

Study Arms (1)

Dapagliflozin

EXPERIMENTAL

* Dapagliflozin will be initiated once daily approximately 6 weeks prior to planned prostatectomy * Dapagliflozin will be given at 10 mg by mouth once daily for 4 weeks (days 1-28) prior to prostatectomy.

Drug: Dapagliflozin

Interventions

Dapagliflozin DRUG

-The 10 mg dose is reflective of current clinical practice for diabetes and heart failure

Also known as: Farxiga

Dapagliflozin

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed localized prostatic adenocarcinoma. Patients with primarily neuroendocrine/small cell histology will be excluded.
• Patients with prostatic adenocarcinoma in one of the following risk groups as defined by NCCN criteria:
• Unfavorable intermediate risk. Intermediate risk is defined as having no high-risk or very high-risk factors and having at least one of the following intermediate risk factors (IRFs):
• cT2b-cT2c
• Grade Group 2 or 3
• PSA 10-20 ng/mL
• Unfavorable intermediate risk additionally must have one or more of the following:
• or 3 IRFs
• Grade Group 3
• ≥50% biopsy cores positive (eg, ≥ 6 of 12 cores) OR
• High-risk, which is defined as not meeting very high-risk criteria and having at least one of the following high-risk features:
• cT3-cT4
• Grade Group 4 or 5
• PSA \> 20 ng/mL OR
• Very high-risk, which is defined as meeting at least two of the following criteria:

You may not qualify if:

• Current or previous treatment with SGLT2i or thiazolidinedione.
• Currently receiving regularly scheduled systemic steroids in the form of prednisone or dexamethasone (more than 10 mg prednisone daily or equivalent). Topical steroid ointments or creams for occasional skin rash is allowed.
• A history of other malignancy with the exceptions of malignancies for which all treatment was completed at least 2 years before registration with no evidence of disease and locally treated skin squamous or basal cell carcinoma.
• History of stroke or transient ischemic attack in the last 5 years.
• Patients with type 1 diabetes mellitus will be excluded or patients with insulin-requiring diabetes mellitus will be excluded. Only patients with well-controlled type 2 diabetes mellitus will be allowed.
• Screening HbA1c \> 10%, unless approved by endocrinologist.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dapagliflozin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, peripheral arterial disease, ketoacidosis, severe kidney disease (estimated glomerular filtration rate eGFR \< 30 mL/min/1.73m2), symptomatic hypotension, and chronic/frequent urinary tract infections or yeast infections.
• Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
• Any evidence of pelvic instrumentation (i.e. hip arthroplasty) that would obscure and/or limit prostate MRI evaluation at the discretion of the investigator, or any type of medical device that would be incompatible with MRI imaging.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

dapagliflozin

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

• Melissa A Reimers, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa A Reimers, M.D.

CONTACT

314-362-5740; mreimers@wustl.edu

Study Design

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

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 14, 2021
• Study Start: June 4, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)