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

Dapagliflozin Combined With Next-generation Hormonal Agent (NHA) Versus Single NHA in Participants With Metastatic Castrate-resistant Prostate Cancer: a Phase 2, Multicenter, Open-label, Randomized Controlled Trial

Dapagliflozin is a well-established medication being marketed and used for treatment Type 2 diabetes mellitus (T2DM). In retrospective cohort studies done by our team, we found that metastatic prostate cancer patients who received Dapagliflozin together with standard anti-cancer treatment, androgen deprivation therapy (ADT) combined with novel hormonal agent (NHA), had better tumor control than those having ADT and NHA.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Dapagliflozin (10mg Tab); Drug: standard medical care (ADT + NHA)

Detailed Description

Androgen deprivation therapy (ADT) combined with novel hormonal agent (NHA) is a standard treatment for metastatic castrate-resistant prostate cancer (mCRPC) but treatment failure and side effects remain significant concerns. Researchers are identifying non-castrating therapies to improve treatment tolerance and quality of life. Recently, the anti-tumor effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors has been revealed in vitro, vivo, and population-based observational studies. However, only one phase I trial has assessed their safety in PCa, and no randomized controlled trial (RCT) has evaluated their efficacy.

A phase 2 multicenter, open-label RCT will be performed in Queen Mary Hospital, Ruijin Hospital and Huashan Hospital (subject to Ethics Committee approval at each center) with 60 mCRPC patients proposed to be recruited. Data will be collected through radiological scan, laboratory test and case report form. Eligible patients will be randomized into two treatment groups with a 1:1 ratio. Patients in the test group will receive dapagliflozin on top of NHA plus ADT while those in the control group will receive standard of care NHA plus ADT. The primary outcome is radiographic progression-free survival. Secondary outcomes include overall survival, biomedical recurrence-free survival, time to first subsequent anti-cancer therapy, time to treatment failure, objective response rate and duration of response. Exploratory outcomes include treatment-related adverse events, quality of life, fear of cancer recurrence, and severity of pain. The primary analysis is efficacy analysis based on the intention-to-treat population. Hazard ratios will be calculated using Cox regression. Interim and finial analyses will be performed upon different study stages.

This study will be the first RCT to evaluate the efficacy and safety of SGLT2 inhibitors combined with the first-line next-generation hormonal agent (NHA) for mCRPC treatment. Given their general tolerability and clinical use, repurposing SGLT2 inhibitors as a non-castrating therapy may lead to better outcomes for PCa patients. Findings of this study will inform a novel combination therapy for advanced PCa, potentially enhancing clinical practice guidelines for its treatment and management in Hong Kong and mainland China

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 852-22554852; Email: stac@hku.hk

Study Locations

• China
  • Shanghai, China
    • Ruijin Hospital
    • Contact: Xiaohao Ruan, MD; Phone Number: 021-64370045; Email: rxh13277@rjh.com.cn
  • Shanghai, China
    • Huashan Hospital
    • Contact: Wu, MD; Phone Number: 021-96999176; Email: ys_wu1@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; dapagliflozin 10 mg daily along with standard medical care (NHA + ADT)	Drug: Dapagliflozin (10mg Tab); Dapagliflozin (10mg Tab); Drug: standard medical care (ADT + NHA); standard medical care for metastatic prostate cancer (ADT + NHA), the choice of NHA and ADT to be agreed among participant and treating physician with dosage and frequency according to local guideline. Surgical castration is also acceptable as ADT.
Active Comparator: Control; Standard of Care (ADT + NHA)	Drug: standard medical care (ADT + NHA); standard medical care for metastatic prostate cancer (ADT + NHA), the choice of NHA and ADT to be agreed among participant and treating physician with dosage and frequency according to local guideline. Surgical castration is also acceptable as ADT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival of prostate cancer per RECIST 1.1 criteria	From date of randomization until the date of first disease progression per RECIST 1.1 criteria, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	From date of randomization until the date of date of death from any cause, assessed up to 60 months
Adverse Event	Adverse Event of combination therapy (dapagliflozin + ADT + NHA)	All adverse events will be evaluated once every 3 months since the date of randomization, until 1 year after the end of treatment, or resolution of any treatment related adverse event, whichever is later.
Duration of response	The time from randomization to disease progression or death, only in patients who achieve complete or partial response	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

Collaborators and Investigators

• Sponsor: Yung NA
• Collaborators: Huashan Hospital; Ruijin Hospital
• Investigators: Principal Investigator: Yung Na, BM, MD, MPH, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): October 30, 2030

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: prostate cancer; sglt2
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Androgen Antagonists; dapagliflozin
• Other Study ID Numbers: HKURO202502

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No