Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · May 10, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a medication called dapagliflozin to see how well it is tolerated and whether it is safe for men with high-risk localized prostate cancer before they undergo surgery to remove the prostate. The trial is looking for men aged 18 and older who have been diagnosed with certain types of prostate cancer that are considered high-risk based on specific criteria, such as the size of the tumor or certain cancer characteristics. Participants must also be planning to have surgery as their main treatment.

If you join this trial, you will take dapagliflozin daily for four weeks before your surgery. Throughout the study, doctors will monitor your health to ensure the medication is safe for you. It’s important to note that certain health conditions and previous treatments may make you ineligible for the study, so an assessment will be done before enrollment. This trial aims to gather information that could help improve treatment options for men facing similar health challenges.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • Histologically or cytologically confirmed localized prostatic adenocarcinoma. Patients with primarily neuroendocrine/small cell histology will be excluded.
• • Patients with high risk or very high risk prostatic adenocarcinoma as defined by NCCN criteria.
• * High risk is defined by NCCN as meeting at least one of the following criteria:
• • T3a
• • grade group 4 or 5
• • PSA \> 20
• * Very high risk is defined by NCCN as meeting at least one of the following criteria:
• • T3b-T4
• • primary Gleason pattern 5
• • 2-3 high risk features \*\*\> 4 cores with grade group 4 or 5
• • 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.