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Radium-223 for High-Volume Metastatic Hormone Sensitive Prostate Cancer (GUARD-QUANTUM)

16 luglio 2026 aggiornato da: Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD

Quantitative Unified Assessment of Novel Triplet Therapy and Unconventional Maintenance With Radium-223 for High-Volume Metastatic Hormone Sensitive Prostate Cancer: A Phase II Pilot Trial

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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

Tipo di studio

Interventistico

Iscrizione (Stimato)

50

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Spagna
      • Barcelona, Spagna, 08036
        • Hospital Clínic de Barcelona
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Barcelona, Spagna, 08041
        • Hospital Santa Creu i Sant Pau
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Las Palmas de Gran Canaria, Spagna, 35016
        • Complejo Hospitalario Universitario Materno-Infantil de Gran Canaria (CHUIMI)
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Madrid, Spagna, 28040
        • Hospital Clínico San Carlos
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Madrid, Spagna, 28041
        • Hospital Universitario 12 de Octubre
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Madrid, Spagna, 28046
        • Hospital Universitario La Paz
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Responsible Person Designated by the Sponsor, M.D., Ph.D.
      • Madrid, Spagna, 28050
        • Hospital Universitario HM Sanchinarro
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Oviedo, Spagna, 33011
        • Hospital Universitario Central de Asturias (HUCA)
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Santander, Spagna, 39008
        • Hospital Universitario Marques de Valdecilla
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Santiago de Compostela, Spagna, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS)
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.
      • Valencia, Spagna, 46009
        • Instituto Valenciano de Oncología (IVO)
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator designed by the Sponsor, M.D., Ph.D.
      • Valladolid, Spagna, 47003
        • Hospital Clínico Universitario de Valladolid (HCUV)
        • Contatto:
          • A responsible person Designated by the Sponsor
          • Numero di telefono: 0034934344412
          • Email: investigacion@mfar.net
        • Investigatore principale:
          • A Principal Investigator Designated by the Sponsor, M.D., Ph.D.

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

INCLUSION CRITERIA

Subjects must fulfill all of the following inclusion criteria to be eligible for enrollment to the study:

  1. Patients must be fully informed about the study and sign the informed consent form (ICF) before any study specific assessment.
  2. Patients ≥18 years old.
  3. ECOG performance status of 0 to 2 and Charlson score ≤ 3 prior to study entry, after docetaxel.
  4. Patients with histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.

  5. 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:

    1. Received ≥ 4 cycles of docetaxel.
    2. Treatment with docetaxel should be finished ≤ 12 weeks before the first planned dose of Ra223.
    3. Having no progression of the disease after triplet therapy completion and before inclusion.

    Note: patients with prior therapies for locoregional disease are acceptable

  6. Patients should have recovered from any prior toxicity from ADT, darolutamide or docetaxel to CTCAE grade 1 or baseline levels.
  7. Presence of at least 4 bone metastasis on the screening bone scan, with or without lymph node and/or visceral metastases.
  8. Asymptomatic or mildly symptomatic (defined as short form question #3 in Brief Pain Inventory worst pain must be < 4).

  9. 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.

  10. T-score ≥ -2.5 on a DXA scan done in the past 12 months. A DXA scan performed during the screening period will be encouraged but not mandated.

  11. 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):

    1. Absolute neutrophil count (ANC) ≥ 1.5 x109/L;
    2. Platelets ≥ 100 x109/L;
    3. Hemoglobin ≥ 9.0 g/dl;
    4. Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN), except for patients with Gilbert's disease ≤ 5.0 x ULN;
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN;
    6. Creatinine ≤ 1.5 x ULN;
    7. CrCl < 30 mL/min;
    8. Albumin > 25 g/L.
  12. Participants who have pregnant partners must use a condom and those with partners of childbearing potential must use a condom and another adequate birth control measure if engaging in sexual activities during the study treatment period and for at least 1 week after last dose of darolutamide and 6 months after the last dose of Ra223. A highly effective method of birth control is defined as those which result in low failure rate (i.e., less than 1% per year) when used consistently and correctly.

EXCLUSION CRITERIA:

Subjects with any of the following could not enroll in this study:

  1. Presence of tumor lesion in central nervous system through radiologically confirmed diagnosis.
  2. Prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin, in-situ carcinoma or low-grade superficial bladder cancer, or the patient has been free of malignancy for a period of 3 years prior to inclusion).

  3. Patients experiencing progression during previous ADT or meeting criteria for castration resistant prostate cancer (CRPC).

    Note: Prior ADT is allowed.

  4. External irradiation, brachytherapy, or local treatment (including radiofrequency ablation, cryotherapy, high intensity focused ultrasound, etc.) within 4 weeks prior to the first dose of study treatment.
  5. Received prior chemotherapy for prostate cancer other than as part of first-line triplet therapy for mHSPC.
  6. Major surgery within 4 weeks prior to treatment.
  7. Prior hemibody external radiotherapy.
  8. Corticosteroids are allowed only at a dose ≤ 10 mg of prednisone (or equivalent) no matter the indication.

  9. 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.

  10. Plan to receive any other antitumor therapies during this trial.
  11. Treatment with an investigational drug within the previous 4 weeks, or planned during the treatment period.

  12. Any other serious illness or medical condition such as, but not limited to:

    1. Any uncontrolled infection ≥ Grade 2 according to NCI-CTCAE v6.0;
    2. Gastrointestinal disorder affecting absorption (e.g., gastrectomy or active peptic ulcer disease);
    3. Crohn's disease or ulcerative colitis;
    4. Osteonecrosis of the jaw;
    5. Non-malignant bone disease with an osteoblastic activity;
    6. Bone marrow dysplasia;
    7. Fecal incontinence;
    8. Life-threatening illness unrelated to cancer.

  13. Significant cardiovascular disease including:

    1. Uncontrolled angina within 3 months prior to screening;
    2. Congestive heart failure New York Heart Association (NYHA) class III or IV, or patients with history of congestive heart failure NYHA class III or IV in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%. Of note, MUGA scans at baseline will not be mandated.
    3. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
    4. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
    5. Uncontrolled hypertension as indicated by a resting systolic blood pressure > 160 millimeters of mercury (mm Hg) or diastolic blood pressure > 100 mm Hg at screening; Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to inclusion. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 160/100 mm Hg in order for a patient to be eligible for the study.
  14. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs. No known hypersensitivity to Ra223 (refer to summary of product characteristics [SmPC]).
  15. Contraindication to both CT and MRI contrast agents.
  16. Contraindications for the use of bisphosphonates or denosumab as per physician judgment.
  17. Involvement in another therapeutic trial involving an experimental drug.
  18. Drug or alcohol abuse.
  19. Any medical condition that in the opinion of the investigator will negatively affect patients' clinical status when participating in this trial.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: QUANTUM intervention

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
Droga: Ra223
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.
Droga: Darolutamide Oral Tablet
Darolutamide at 600 mg twice daily. Darolutamide administration will continue until progression, unacceptable toxicity, withdrawal or death, whichever comes first.
Altro: Androgen Deprivation Therapy (ADT)
Standard of care ADT (surgical or drug). Administration will continue until progression, unacceptable toxicity, withdrawal or death, whichever comes first.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Treatment compliance
Lasso di tempo: Throughout the study treatment period, approximately 6 months
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.
Throughout the study treatment period, approximately 6 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Prostate-specific antigen (PSA) response rates
Lasso di tempo: Throughout the study period, approximately 18 months
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).
Throughout the study period, approximately 18 months
Total alkaline phosphatase response rates
Lasso di tempo: Throughout the study period, approximately 18 months
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.
Throughout the study period, approximately 18 months
Radiographic progression-free survival (rPFS)
Lasso di tempo: Throughout the study period, approximately 18 months
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.
Throughout the study period, approximately 18 months
Time to pain progression
Lasso di tempo: Throughout the study period, approximately 18 months

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
Throughout the study period, approximately 18 months
Time to next systemic antineoplastic therapy
Lasso di tempo: Throughout study period, approximately 18 months
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.
Throughout study period, approximately 18 months
Time to castration resistance
Lasso di tempo: Throughout the study period, approximately 18 months
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.
Throughout the study period, approximately 18 months
Overall survival (OS)
Lasso di tempo: Throughout the study period, approximately 18 months
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.
Throughout the study period, approximately 18 months
Time to symptomatic skeletal event
Lasso di tempo: Throughout the study period, approximately 18 months

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.
Throughout the study period, approximately 18 months
Incidence of dose interruption
Lasso di tempo: Throughout the study treatment period, approximately 6 months
Percentage of patients experiencing dose interruptions
Throughout the study treatment period, approximately 6 months
Health-related quality of life (HRQoL) through EQ-5D-5L
Lasso di tempo: Throughout the study period, approximately 18 months

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"
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)
Lasso di tempo: Throughout the study period, approximately 18 months

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.
Throughout the study period, approximately 18 months

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Assessment of disease volume by novel imaging modalities (Prostate-Specific Membrane Antigen Positron Emission Tomography [PET-PSMA])
Lasso di tempo: Throughout the study period, approximately 18 months
Patients will be assessed through PT-PSMA. The volume of disease will be reported trhough time. Best tumor size reduction will be reported
Throughout the study period, approximately 18 months
Biomarkers
Lasso di tempo: 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
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.
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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Alianza multidisciplinar para la investigación de los tumores genitourinarios -GUARD

Collaboratori

Bayer
MFAR

Investigatori

  • Cattedra di studio: David Lorente, M.D., Ph.D., Instituto Valenciano de Oncología
  • Cattedra di studio: Guillermo de Velasco, M.D., Ph.D., Hospital Universitario 12 de Octubre

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2026

Completamento primario (Stimato)

1 dicembre 2029

Completamento dello studio (Stimato)

1 dicembre 2029

Date di iscrizione allo studio

Primo inviato

2 luglio 2026

Primo inviato che soddisfa i criteri di controllo qualità

16 luglio 2026

Primo Inserito (Effettivo)

21 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

21 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

16 luglio 2026

Ultimo verificato

1 luglio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • SC 2025-01 // 23161
  • 2026-525550-11-00 (Ctis)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Ra223

  • European Organisation for Research and Treatment...
    Bayer; Latin American Cooperative Oncology Group; UNICANCER; Astellas Pharma Europe... e altri collaboratori
    Attivo, non reclutante
    Fase III Radium 223 mCRPC-PEACE III (PEACE III)
    Cancro alla prostata
    Spagna, Belgio, Francia, Italia, Regno Unito, Danimarca, Canada, Irlanda, Brasile, Norvegia, Polonia, Svizzera

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in France

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi