A Phase 2 interventional study of Ra223 and Darolutamide Oral Tablet in Metastatic Hormone-Sensitive Prostate Cance, sponsored by Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD. Not yet recruiting at 12 sites in Spain. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-21.
Sponsored by Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD · Phase 2, Interventional, and Treatment
GUARD-QUANTUM is a prospective, phase II, single-arm, non-randomized, non-blinded, investigator-initiated study. The rationale behind studying this combination lies in the potential additive or synergistic benefits that may arise from concurrently targeting androgen receptor signaling pathways and bone metastases.
The trial will enroll competitively up to 50 patients with mHSPC and high volume disease (i.e. ≥4 bone metastatic foci in Tc-99m bone scanning, with at least one focus located outside the pelvis or vertebral bodies in the spine AND/OR visceral metastasis shown on computed tomography or magnetic resonance imaging not including lymph nodes). Patients should have started and be on treatment as per standard of care with first-line triplet therapy consisting of chemical or surgical androgen deprivation therapy (ADT), docetaxel and darolutamide. At least four cycles of docetaxel should have been administered and the last dosing of docetaxel be \< 12 weeks prior the first planned dose of Ra223. Patients should have a good performance status (ECOG PS 0-2 and Charlson score ≤ 3) and have recovered from any prior toxicity from triplet therapy. Previous treatments other than chemotherapy for locoregional disease are acceptable.
Additionally to the IMPs and AXMPs, the study includes the administration of at least two doses of a bone protecting agent (zoledronic acid or denosumab) is required before the first administration of Ra223, and the bone protecting agent should have been started at least 6 weeks before the first administration of Ra223. Patients should also start treatment with vitamin D and calcium supplements
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's planned enrollment of 50 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD is the lead sponsor of 3 studies on the registry; 3 are open to participants now.
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Subjects must fulfill all of the following inclusion criteria to be eligible for enrollment to the study:
Patients should have received triplet therapy with ADT (luteinizing hormone releasing hormone analogue (LHRHA) for continuous treatment or previous bilateral orchidectomy), docetaxel and darolutamide as first-line therapy for mHSPC. The following conditions apply:
Note: patients with prior therapies for locoregional disease are acceptable
Patients should be willing to initiate or continue bisphosphonates /denosumab, calcium and vitamin D supplements (Section 7.4.4) prior to the first dose of Ra223.
Note: Patients must start treatment with a bone protecting agent (at doses used to reduce the incidence of skeletal related events) before the time of signing the ICF. A minimum of two doses is recommended before the first administration of Ra223. The first administration of Ra223 should be scheduled at least 6 weeks after the first administration of the bone protecting agent.
Adequate organ and bone marrow function as follows (subject must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory):
EXCLUSION CRITERIA:
Subjects with any of the following could not enroll in this study:
Patients experiencing progression during previous ADT or meeting criteria for castration resistant prostate cancer (CRPC).
Note: Prior ADT is allowed.
Receiving abiraterone treatment as part of the first-line triplet therapy for mHSPC.
Note: An increased risk of death and fractures was observed in a clinical study in which Ra223 was added to abiraterone acetate and prednisone/prednisolone in patients with asymptomatic or mildly symptomatic CRPC and this is the rationale to not include patients with this combination.
Any other serious illness or medical condition such as, but not limited to:
Significant cardiovascular disease including:
Six intravenous administrations of Radium-223 chloride, in a dose of 55 kBq/kg body weight standard dose with a treatment interval between administrations of 4 weeks. Treatment with Ra223 could be prematurely discontinued in case of progression, unacceptable toxicity, withdrawal or death. Patients received backgrount therapy with ADT and darolutamide
Drug: Ra223 · Drug: Darolutamide Oral Tablet · Other: Androgen Deprivation Therapy (ADT)
Six intravenous administrations of Radium-223 chloride, in a dose of 55 kBq/kg body weight standard dose with a treatment interval between administrations of 4 weeks. Treatment with Ra223 could be prematurely discontinued in case of progression, unacceptable toxicity, withdrawal or death.
Darolutamide at 600 mg twice daily. Darolutamide administration will continue until progression, unacceptable toxicity, withdrawal or death, whichever comes first.
Standard of care ADT (surgical or drug). Administration will continue until progression, unacceptable toxicity, withdrawal or death, whichever comes first.
Treatment compliance
Measured as the total number of cycles administered to each patient. Patients will be categorized in two groups, complete treatment compliance (complete ≥5 cycles of Ra223) and incomplete treatment compliance (complete \<5 cycles of Ra223). The proportion of patients in each category and their 95% confidence interval (CI) calculated by Clopper-Pearson will be given.
Time frame: Throughout the study treatment period, approximately 6 months
Prostate-specific antigen (PSA) response rates
Response is defined as PSA \<0.02 ng/mL at Ra223 completion. Rate of PSA response is defined as the number of subjects with absolute PSA response, divided by the total number of subjects evaluable for absolute PSA response (with high PSA levels at baseline).
Time frame: Throughout the study period, approximately 18 months
Total alkaline phosphatase response rates
Defined as a reduction of ≥30% from the baseline value, before the first dose of study treatment (Ra223). The ALP response will be assessed only in patients with ALP increased levels at baseline. Percentage of patients who experience these reductions throughout the study period.
Time frame: Throughout the study period, approximately 18 months
Radiographic progression-free survival (rPFS)
Defined from the day of first dose of Ra223 to the day the first event of radiological progression or death (due to any cause) is recorded. Assessed by investigator and defined as motivated by the recommendations of the Prostate Cancer Clinical Trials Working Group 3for the "delay/prevent" objective. rPFS will be estimated by Kaplan-Meier method. Patients who are alive without evidence of radiological progression at their last imaging assessment will be censored at that date.
Time frame: Throughout the study period, approximately 18 months
Time to pain progression
Measured according to Brief Pain Inventory (BPI). Pain progression is defined in patients in the 'pain evaluable' population as: an increase of 2 or more points in the BPI's "worst pain in 24 hours"-score from baseline observed at 2 consecutive evaluations ≥4 weeks apart, or initiation of short or long-acting opioid use for pain. Time-to-pain progression is defined as the time (days) from the first dose of study treatment (Ra223) date, to the date of pain progression
Time frame: Throughout the study period, approximately 18 months
Time to next systemic antineoplastic therapy
This is the interval of time between first dose of study treatment (Ra223) and the first day of initiation of a next line of systemic antineoplastic therapy after the initial scheduled treatment.
Time frame: Throughout study period, approximately 18 months
Time to castration resistance
Defined as the time to PSA progression (according to PCWG3 criteria is defined as the date that a 25% or greater increase and absolute increase of 2 ng/mL or more from the nadir \[lowest at or after baseline\] is documented, which both are confirmed by a second value obtained at least 3 weeks later, including all potential PSA values ≥2 ng/mL above nadir and ≥25% increase above nadir between initial assessment date and confirmation assessment date) with serum testosterone being at castrate level \<0.50 ng/mL, or the time to progression by soft tissue lesions or bone lesions (as described above), whatever comes first.
Time frame: Throughout the study period, approximately 18 months
Overall survival (OS)
Measured from the date of first dose of study treatment (Ra223) to the date of death whatever the cause of death. OS will be estimated by Kaplan-Meier method. Patients who are alive are censored at the date of the most recent follow-up examination.
Time frame: Throughout the study period, approximately 18 months
Time to symptomatic skeletal event
Defined as the time elapsed between the day of first dose of study treatment administration (Ra223) to the day of symptomatic skeletal event recorded for each patient. Symptomatic Skeletal-related events (SSEs) are defined as the first event of: the first use of external-beam radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or non-vertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention.
Time frame: Throughout the study period, approximately 18 months
Incidence of dose interruption
Percentage of patients experiencing dose interruptions
Time frame: Throughout the study treatment period, approximately 6 months
Health-related quality of life (HRQoL) through EQ-5D-5L
The EQ-5D-5L is a standardized, widely used questionnaire designed to measure a person's HRQoL. It evaluates overall health across five distinct dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and provides an actionable index score and a visual assessment of health status. Here we will report the total score: The top of the scale (100) represents "The best health you can imagine". The bottom of the scale (0) represents "The worst health you can imagine"
Time frame: Throughout the study period, approximately 18 months
Health-related quality of life (HRQoL) through National Comprehensive Cancer Network Functional Assessment of Cancer Therapy - Prostate (FACT-P)
The FACT-P is a validated, multidimensional, patient-reported questionnaire used to evaluate the HRQOL of men diagnosed with prostate cancer. It is widely used by clinicians and researchers to track physical, emotional, and social well-being over time. The assessment consists of 39 questions/statements graded on a 5-point Likert scale (ranging from 0 = "not at all" to 4 = "very much"). It is divided into five core domain: physical, social, emotional, functional and prostatic. Here we will report the total score. The total FACT-P score ranges from 0 to 156. Higher scores represent a better health-related quality of life.
Time frame: Throughout the study period, approximately 18 months
Assessment of disease volume by novel imaging modalities (Prostate-Specific Membrane Antigen Positron Emission Tomography [PET-PSMA])
Patients will be assessed through PT-PSMA. The volume of disease will be reported trhough time. Best tumor size reduction will be reported
Time frame: Throughout the study period, approximately 18 months
Biomarkers
Transcriptome and whole genome sequencing to identify biomarkers that correlate with prognosis. Here we will report the most frequent genetic alterations and their prevalence in the study population. The analysis will be done in tumor and blood samples.
Time frame: Tumor archival tissue sample at baseline. Blood samples at baseline, within 7 days before end of Cycle 3 (each cycle is 28 days) and at disease progression
Plan to share: No
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Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD