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.
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:
202107070
- NCT ID:
NCT04887935
Conditions
- Prostate Cancer
- Cancer of Prostate
Interventions
Drug | Synonyms | Arms |
---|
Dapagliflozin | Farxiga | Dapagliflozin |
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
Name | Type | Description | Interventions |
---|
Dapagliflozin | Experimental | 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. | |
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
August 18, 2021