Clinical Trials /

Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer

NCT04887935

Description:

This is a study of the tolerability and safety of neoadjuvant dapagliflozin for patients with 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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer
  • Official Title: Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 21-x178
  • NCT ID: NCT04887935

Conditions

  • Prostate Cancer
  • Cancer of Prostate

Interventions

DrugSynonymsArms
DapagliflozinFarxigaDapagliflozin

Purpose

This is a study of the tolerability and safety of neoadjuvant dapagliflozin for patients with 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.

Trial Arms

NameTypeDescriptionInterventions
DapagliflozinExperimentalDapagliflozin 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.
  • Dapagliflozin

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

          -  Normal bone marrow and organ function as defined below:

               -  Leukocytes ≥ 3,000/mcL

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  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. 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.

          -  HbA1c > 10%, unless approved by endocrinologist. No patients with insulin-requiring
             diabetes mellitus will be allowed.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and severity of toxicities related to dapagliflozin as measured by CTCAE v 5.0
Time Frame:From start of treatment through day 64
Safety Issue:
Description:-Feasibility will be met if 24 patients are enrolled in 24 months

Secondary Outcome Measures

Measure:Percent reduction in prostate tumor size as determined by pre-operative prostate MRI
Time Frame:At the time of pre-operative prostate MRI (estimated to be at week 6)
Safety Issue:
Description:
Measure:Percentage of prostate tumor necrosis
Time Frame:At the time of radical prostatectomy (estimated to be at week 6)
Safety Issue:
Description:
Measure:Change in plasma glucose
Time Frame:From day 1 to day 29
Safety Issue:
Description:
Measure:Change in ketones
Time Frame:From day 1 to day 29
Safety Issue:
Description:
Measure:Change in HbA1C
Time Frame:From baseline to day 29
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

May 19, 2021