Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Cancer of Prostate
• Intervention / Treatment: Drug: Dapagliflozin

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Melissa A Reimers, M.D.; Phone Number: 314-362-5740; Email: mreimers@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Linda R Peterson, M.D.
      • Contact: Melissa A Reimers, M.D.; Phone Number: 314-362-5740; Email: mreimers@wustl.edu
      • Principal Investigator: Melissa A Reimers, M.D.
      • Sub-Investigator: Janet McGill, M.D.
      • Sub-Investigator: Jingqin (Rosy) Luo, Ph.D.
      • Sub-Investigator: Joseph E Ippolito, M.D., Ph.D.
      • Sub-Investigator: Woodson W Smelser, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

      • 2 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:

    • cT3-cT4
    • Grade Group 4 or 5
    • PSA > 40 ng/mL\
• Willing and able to undergo prostate MRI at baseline, with a measurable prostate lesion present.
• Planning to undergo radical prostatectomy as primary treatment for localized prostate cancer.
• At least 18 years of age.
• ECOG performance status ≤ 1

• Adequate bone marrow and organ function as defined below:

  • Leukocytes ≥ 3.0 K/cumm
  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m^2
• Agreement to adhere to Lifestyle Considerations throughout study duration
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; 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; -The 10 mg dose is reflective of current clinical practice for diabetes and heart failure; Other Names: Farxiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Change in glucagon	From screening to day 29

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Foundation for Barnes-Jewish Hospital
• Investigators: Principal Investigator: Melissa A Reimers, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 14, 2021

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin
• Other Study ID Numbers: 202107070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No