Triplet Therapy (Androgen Deprivation Therapy + Darolutamide + Biweekly Docetaxel) for High-risk Metastatic Castration-sensitive Prostate Cancer (TRIC Study): A Study Protocol for Open-labelled Single-Arm Phase II Clinical Trial.

BACKGROUND

Triplet therapy consisting of androgen deprivation therapy (ADT), docetaxel, and an androgen receptor signaling inhibitor (ARSI) has demonstrated survival benefits in patients with metastatic castration-sensitive prostate cancer (mCSPC), particularly those with high-risk disease. However, the feasibility of this intensive regimen is often limited by docetaxel-associated toxicity, especially in Japanese patients. Under the current Japanese health insurance system, darolutamide is the only ARSI approved for use in triplet therapy for mCSPC. Therefore, optimization of docetaxel administration is a key clinical issue.

METHODS

The triplet therapy (androgen deprivation therapy + darolutamide + biweekly docetaxel) for high-risk metastatic castration-sensitive prostate cancer (TRIC) study is an investigator-initiated, single-center, open-label, single-arm phase II clinical trial designed to evaluate the efficacy and safety of triplet therapy consisting of ADT, darolutamide, and biweekly low-dose docetaxel (35 mg/m2 every two weeks) in patients with high-risk mCSPC. High-risk disease is defined according to the castration-sensitive PC classification proposed by Kanazawa University (Canazawa) risk classification, which includes Gleason pattern 5, bone scan index ≥1.5, and lactate dehydrogenase ≥300 IU/L. The primary endpoint is prostate-specific antigen (PSA) response at three and six months. Secondary endpoints include overall survival, time to castration resistance, radiographic progression-free survival, safety, and other clinically relevant outcomes.

RESULTS

This study will prospectively assess the feasibility, safety, and early efficacy of the proposed triplet regimen. PSA response rates, survival outcomes, and treatment-related adverse events will be analyzed to generate preliminary evidence regarding treatment activity and tolerability in this high-risk population.

CONCLUSIONS

The TRIC study will provide important prospective data on a modified triplet therapy tailored to the Japanese clinical setting. The findings are expected to inform future randomized trials and to contribute to the development of optimized treatment strategies for patients with high-risk mCSPC.

TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs) 041240151, registered: December 18, 2025.