RECRUITING

Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

Quick Facts

Study Start:2024-06-04

Study Completion:2026-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04887935

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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).	* 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.

Inclusion Criteria

Exclusion 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).

* 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.

Contacts and Locations

Study Contact

Melissa A Reimers, M.D.

CONTACT

314-362-5740

mreimers@wustl.edu

Principal Investigator

Melissa A Reimers, M.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Melissa A Reimers, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-04

Study Completion Date2026-08-31

Study Record Updates

Study Start Date2024-06-04

Study Completion Date2026-08-31

Terms related to this study

Additional Relevant MeSH Terms

Prostate Cancer
Cancer of Prostate