Dapagliflozin Propanediol for the Treatment of Localized Prostate Cancer

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 National Comprehensive Cancer Network (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 ** Prostate specific antigen (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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• 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)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x IULN
• Estimated glomerular filtration rate estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m^2
• Agreement to adhere to lifestyle considerations throughout study duration
• Ability to understand and willingness to sign an Institutional Review Board (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 or patients with insulin-requiring diabetes mellitus will be excluded. Only patients with well-controlled type 2 diabetes mellitus will be allowed
• Hemoglobin A1c (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/1.73 m^2), symptomatic hypotension, and chronic/frequent urinary tract infections or yeast infections
• Patients with human immunodeficiency virus (HIV) are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (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