Targeted radiation added to darolutamide and hormone therapy for metastatic prostate cancer

Trial details

Who runs it

West China Hospital

Trial code

NCT07649421

Record updated

10 September 2026

Original description

This is a multicenter, randomized, open-label phase 2 study for men with metastatic hormone-sensitive prostate cancer. About 254 participants will first receive 6 months of darolutamide plus androgen deprivation therapy. Participants whose cancer has not progressed and who still have active tumor lesions on prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) will then be randomly assigned to one of two groups. One group will continue darolutamide plus androgen deprivation therapy. The other group will receive stereotactic body radiotherapy (SBRT) to all active tumor lesions identified by PSMA PET/CT, while continuing darolutamide plus androgen deprivation therapy. The main purpose of this study is to find out whether adding PSMA PET/CT-guided SBRT can help participants live longer without tumor growth seen on scans or death. The study will also evaluate prostate-specific antigen (PSA) changes, time to castration-resistant prostate cancer, overall survival, side effects, and quality of life.Read full original descriptionShow less

A Multicenter, Prospective, Randomized Controlled Phase II Trial of PSMA PET/CT-Guided Stereotactic Body Radiotherapy Combined With Darolutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer

This is a multicenter, randomized, open-label phase 2 study for men with metastatic hormone-sensitive prostate cancer. About 254 participants will first receive 6 months of darolutamide plus androgen deprivation therapy. Participants whose cancer has not progressed and who still have active tumor lesions on prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) will then be randomly assigned to one of two groups. One group will continue darolutamide plus androgen deprivation therapy. The other group will receive stereotactic body radiotherapy (SBRT) to all active tumor lesions identified by PSMA PET/CT, while continuing darolutamide plus androgen deprivation therapy. The main purpose of this study is to find out whether adding PSMA PET/CT-guided SBRT can help participants live longer without tumor growth seen on scans or death. The study will also evaluate prostate-specific antigen (PSA) changes, time to castration-resistant prostate cancer, overall survival, side effects, and quality of life.

Inclusion: Male participants aged ≥18 years and <85 years; Histologically confirmed prostate adenocarcinoma; No neuroendocrine carcinoma, ductal adenocarcinoma, small-cell carcinoma, signet-ring cell carcinoma, or sarcomatoid carcinoma component; Metastatic prostate cancer confirmed by imaging and/or pathological evidence; Baseline PSMA PET/CT assessment demonstrates a total of ≤20 metastatic lesions; No prior radical prostatectomy or radiotherapy for prostate cancer; No prior systemic anti-tumor therapy that may affect the efficacy assessment of this study, including androgen receptor signaling inhibitors (ARSIs; e.g., abiraterone, enzalutamide, apalutamide, rezvilutamide, or darolutamide), chemotherapy, PARP inhibitors, radionuclide therapy, or other such treatments; Short-term androgen deprivation therapy (ADT) and/or first-generation antiandrogen therapy prior to enrollment is permitted, provided that the interval from the first initiation of any such treatment to the date of enrollment does not exceed 3 months (≤12 weeks); Expected survival >12 months; Able to understand the study and voluntarily sign written informed consent; Able and willing to comply with study visits and protocol procedures; Willing to provide tumor tissue, blood, and other biological samples as required by the study protocol; Absolute neutrophil count ≥1.5 × 10\^9/L; Platelet count ≥100 × 10\^9/L; Hemoglobin ≥90 g/L; Total bilirubin ≤1.5 × upper limit of normal; Alanine aminotransferase and aspartate aminotransferase ≤2.5 × upper limit of normal; Serum albumin ≥20 g/L; Serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥50 mL/min; Eastern Cooperative Oncology Group performance status ≤2.

Exclusion: Current or prior history of another primary malignancy; Prior radical prostatectomy; Prior external beam radiotherapy; Prior radical or ablative local therapy for prostate cancer; Prior treatment with an androgen receptor signaling inhibitor, including abiraterone, enzalutamide, apalutamide, rezvilutamide, or darolutamide; Prior chemotherapy for prostate cancer; Major surgery within 4 weeks before enrollment; Serious trauma within 4 weeks before enrollment; Contraindication to radiotherapy; Inability to maintain the required body position for radiotherapy; Unacceptable toxicity during the 6-month run-in period of androgen deprivation therapy plus darolutamide before randomization; Arterial thrombotic, embolic, or ischemic event within 6 months before enrollment; Myocardial infarction within 6 months before enrollment; Unstable angina within 6 months before enrollment; Cerebrovascular accident within 6 months before enrollment; Transient ischemic attack within 6 months before enrollment; Symptomatic hypercalcemia requiring continuous bisphosphonate therapy; History of abdominal fistula within 6 months before enrollment; History of gastrointestinal perforation within 6 months before enrollment; History of intra-abdominal abscess within 6 months before enrollment; History of another malignancy within 3 years that differs from the study cancer in primary site or histology; History of papillary thyroid carcinoma is allowed if it is well controlled; History of basal cell carcinoma of the skin is allowed if it is well controlled; History of squamous cell carcinoma of the skin is allowed if it is well controlled; History of cervical carcinoma in situ is allowed if it is well controlled; Severe pelvic infection; History of allergy to PET/CT tracer; Disease progression during the 6-month run-in period of androgen deprivation therapy plus darolutamide before randomization; Allergy to any component of the study treatment; Active or poorly controlled serious infection; Human immunodeficiency virus infection; Acute or chronic active hepatitis C infection, defined as positive hepatitis C virus antibody with hepatitis C virus RNA >15 IU/mL; Active pulmonary tuberculosis; Other serious infectious disease; New York Heart Association class III or IV congestive heart failure; Persistent symptomatic arrhythmia; Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg; Medical condition requiring warfarin or coumarin anticoagulation therapy; Uncontrolled adrenal insufficiency; Severe non-healing ulcer; Gastrointestinal disease that may impair absorption; Active peptic ulcer disease; History of small bowel resection that may impair drug absorption; Any other medical or psychological condition that, in the investigator's judgment, may affect participant safety, compliance, or study integrity; Any condition that, in the investigator's judgment, makes the participant unsuitable for this study; Acute or chronic active hepatitis B infection, defined as positive hepatitis B surface antigen with hepatitis B virus DNA >1 × 10\^3/mL; Left ventricular ejection fraction below the lower limit of normal on repeated echocardiographic assessments; Uncontrolled hypercalcemia, defined as ionized calcium >1.5 mmol/L, total calcium >12 mg/dL, or corrected serum calcium above the upper limit of normal; Other acute or chronic disease, psychiatric disorder, or laboratory abnormality that may increase the risk associated with study participation or study treatment; Other acute or chronic disease, psychiatric disorder, or laboratory abnormality that may interfere with interpretation of study results; Spinal cord compression; Active enteritis; Nuclear medicine assessment showing super bone imaging; Marked discordance between PSMA PET/CT and FDG PET/CT findings; No active tumor lesion on PSMA PET/CT after the 6-month run-in period; Uncontrolled atrial fibrillation; Severe non-healing wound; Uncontrolled nausea; Uncontrolled vomiting; Uncontrolled diarrhea.

ClinicalTrials.gov NCT07649421