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Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer

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ClinicalTrials.gov Identifier: NCT04887935
Recruitment Status : Not yet recruiting
First Posted : May 14, 2021
Last Update Posted : May 19, 2021
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Cancer of Prostate Drug: Dapagliflozin Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer
Estimated Study Start Date : April 30, 2022
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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 Name: Farxiga




Primary Outcome Measures :
  1. Frequency and severity of toxicities related to dapagliflozin as measured by CTCAE v 5.0 [ Time Frame: From start of treatment through day 64 ]
  2. Number of patients enrolled in 24 months [ Time Frame: Through 24 months ]
    -Feasibility will be met if 24 patients are enrolled in 24 months


Secondary Outcome Measures :
  1. 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) ]
  2. Percentage of prostate tumor necrosis [ Time Frame: At the time of radical prostatectomy (estimated to be at week 6) ]
  3. Change in plasma glucose [ Time Frame: From day 1 to day 29 ]
  4. Change in ketones [ Time Frame: From day 1 to day 29 ]
  5. Change in HbA1C [ Time Frame: From baseline to day 29 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04887935


Contacts
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Contact: Melissa A Reimers, M.D. 314-362-5740 mreimers@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Contact: Melissa A Reimers, M.D.    314-362-5740    mreimers@wustl.edu   
Principal Investigator: Melissa A Reimers, M.D.         
Sub-Investigator: Linda R Peterson, M.D.         
Sub-Investigator: Joseph E Ippolito, M.D., Ph.D.         
Sub-Investigator: George Andriole, M.D.         
Sub-Investigator: Janet McGill, M.D.         
Sub-Investigator: Jingqin (Rosy) Luo, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Melissa A Reimers, M.D. Washington University School of Medicine
Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT04887935    
Other Study ID Numbers: 21-x178
First Posted: May 14, 2021    Key Record Dates
Last Update Posted: May 19, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs