Clinical trial NCT04887935: Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer
Official title: Pilot Clinical Trial of Neoadjuvant SGLT2 Inhibition in High-Risk Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostate Cancer
Cancer of Prostate
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: The Foundation for Barnes-Jewish Hospital
First posted: 2021-05-14
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Frequency and severity of toxicities related to dapagliflozin as measured by CTCAE v 5.0
timeFrame: From cycle 1 day 1 (the cycle is 28 days in length) through 30 days after prostatectomy (approximately day 64)
measure: Proportion of patients who are able to successfully complete at least 80% of the planned dapagliflozin doses and undergo radical prostatectomy
timeFrame: At approximately 6 weeks
Secondary outcomes:
measure: MRI quantified change in tumor size from screening to post-treatment
timeFrame: At the time of pre-operative prostate MRI (estimated to be at week 6)
measure: Degree of tumor necrosis/shrinking
timeFrame: From screening to time of radical prostatectomy (estimated to be at week 6)
measure: Change in plasma glucose
timeFrame: From screening to day 29
measure: Change in C-peptide
timeFrame: From screening to day 29
measure: Change in HbA1C
timeFrame: From screening to day 29
measure: Change in glucagon
timeFrame: From screening to day 29
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Melissa A Reimers, M.D.
role: PRINCIPAL_INVESTIGATOR
References: