Dapagliflozin Combined With Next-generation Hormonal Agent (NHA) Versus Single NHA in Participants With Metastatic Castrate-resistant Prostate Cancer

Inclusion Criteria:

* Age of 18 years and above
* Histologically or cytologically confirmed diagnosis of prostatic adenocarcinoma without neuroendocrine/ small cell histology;
* PCa progression while receiving ADT (or post bilateral orchiectomy) within 6 months before screening: two consecutive rising PSA levels, radiographic soft tissue or bone progression;
* Current evidence of metastatic disease by radiological scan;
* Decided to receive any of the NHA (including Abiraterone Acetate, Enzalutamide, Apalutamide or Darolutamide) under standard of care setting, or started NHA for no more than 28 days at the time of treatment period start;
* Ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<1.7 nM);
* Naïve of taxane-based chemotherapy regimens;
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
* Normal hematologic and organ function as defined below: (a) leukocytes ≥ 3,000/mcL; (b) absolute neutrophil count ≥ 1,500/mcL; (c) platelets ≥ 100,000/mcL; (d) total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN); (e) AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN; (f) estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m2;
* Ability to understand and willingness to sign an IRB-approved written informed consent document.

Exclusion Criteria:

* Current or previous treatment with SGLT2 inhibitors or thiazolidinedione;
* Presence of type 1 diabetes mellitus, insulin-requiring diabetes mellitus or poorly controlled diabetes mellitus (i.e., HbA1c \> 10%, unless approved by endocrinologist);
* Presence of malignancies other than prostate cancer within two years prior to study enrollment;
* Disease progressed during or after treatment with one NHA;
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dapagliflozin;
* Clinically significant abnormal serum potassium or sodium level;
* Presence of uncontrolled comorbidities including but not limited to ongoing or active infection (e.g., HIV, HBV, HCV and tuberculosis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, peripheral arterial disease, ketoacidosis, severe kidney disease, symptomatic hypotension, and chronic/frequent urinary tract infections or yeast infections;
* Participation in another clinical trial with therapeutic intent within 28 days prior to enrollment;
* Inability to swallow capsules/tablets
* Any medical conditions that might deem unsafe or contraindicated for inclusion in the clinical trial, per investigator's discretion