Using dapagliflozin before surgery for high-risk prostate cancer

Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer

This study is testing if the diabetes drug dapagliflozin is safe and well-tolerated when given to men with high-risk prostate cancer before their surgery.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Washington University School of Medicine (other)
• Drugs / interventions: prednisone
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT04887935 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of dapagliflozin, an SGLT2 inhibitor, administered for four weeks prior to radical prostatectomy in patients with high-risk localized prostatic adenocarcinoma. The primary aim is to determine if this treatment is well-tolerated in this specific patient population. Eligible participants must have confirmed localized prostate cancer and meet specific high-risk criteria as defined by NCCN guidelines. The study will involve monitoring patients' responses and any adverse effects during the treatment period.

Who should consider this trial

Good fit: Ideal candidates are adult males aged 18 and older with high-risk or very high-risk localized prostatic adenocarcinoma planning to undergo radical prostatectomy.

Not a fit: Patients with neuroendocrine or small cell histology of prostate cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve surgical outcomes and overall management of high-risk prostate cancer patients.

How similar studies have performed: While this specific approach is novel, similar studies involving SGLT2 inhibitors in cancer treatment have shown promising results.

Eligibility criteria

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 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).

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.

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (RECRUITING)

Study contacts

• Principal investigator: Melissa A Reimers, M.D. — Washington University School of Medicine
• Study coordinator: Melissa A Reimers, M.D.

Conditions: Prostate Cancer, Cancer of Prostate