Terapia radiofarmacéutica personalizada frente a actividad fija 177LU-PSMA-617 (Prodigy-2) (PRODIGY-2)
Endoradioterapia guiada con dosimetría de membrana de membrana específica de próstata: un estudio piloto controlado al azar, de ciego único de la terapia radiofarmacéutica personalizada versus actividad fija 177LU-PSMA-617 (Prodigy-2)
The goal of this clinical trial is to assess if a personalized regime of 177Lu-PSMA-617 (Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto) is feasible and safe in a population of patients with metastatic castrate-resistant prostate cancer (mCRPC). The main questions it aims to answer are:
- Can the administered activity (cumulative or per-cycle) be increased in a majority of participants?
- What is the incidence of some specific adverse reactions during the treatment?
Researchers will compare participants receiving a personalized regime to participants receiving the standard fixed-activity regime of 177Lu-PSMA-617 to see if the activity can be safely increased through personalization based on renal dosimetry (i.e. the measure of how much radiation is actually delivered to the kidney).
Participants will receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks and be regularly evaluated with imaging and laboratory tests, as well as with questionnaires.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Marie-Christine Dubé, Ph.D.
- Número de teléfono: 418-525-4444
- Correo electrónico: marie-christine.dube@crchudequebec.ulaval.ca
Ubicaciones de estudio
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Quebec
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Québec, Quebec, Canadá, G1R2J6
- Reclutamiento
- CHU de Québec-Université Laval
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Contacto:
- Marie-Christine Dubé, Ph.D.
- Número de teléfono: 418-525-4444
- Correo electrónico: marie-christine.dube@crchudequebec.ulaval.ca
-
Investigador principal:
- Jean-Mathieu Beauregard, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Patient aged ≥18 years with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma;
- Castration-resistant prostate cancer, as defined as disease progressing despite castration by orchiectomy or ongoing androgen deprivation therapy (serum testosterone level ≤ 1.7 nmol/dL within 60 days from first cycle);
- Biochemically progressive mCRPC with rising PSA level, defined by PCWG3 criteria (sequence of two rising values above a baseline at a minimum of 1-week intervals, with the second of these within 60 days from first cycle);
- PSA ≥2 ng/mL ;
- Prior treatment with at least one ARPI;
- PSMA-expressing cancer, with significant PSMA expression defined as SUVpeak in at least one lesion that is superior to SUVmean of the liver on PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL), within 45 days prior to randomization;
- ECOG Performance status 0 to 2;
- Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m^2;
- Albumin ≥ 25 g/L;
- Platelets ≥ 100x10^9/L;
- Neutrophils ≥ 1.5x10^9/L;
- Hemoglobin ≥ 90 g/L without transfusion in the past 4 weeks;
- Signed, written informed consent
Exclusion Criteria:
- PSMA-PET "superscan" (i.e. extensive/diffuse PSMA-positive bone involvement);
- Site(s) of disease that are FDG-positive, defined as SUVpeak in at least one lesion that is superior to twice (2x) SUVmean of the liver, and PSMA-negative (as above), within 45 days prior to randomization;
- Prior treatment with more than two lines of chemotherapy for mHSPC and/or mCRPC (a line is counted if at least 2 cycles were administered; adjuvant and neoadjuvant chemotherapy does not count towards the maximum of two lines);
- Prior PSMA-directed radiopharmaceutical therapy (radium-223 is allowed);
- Known CNS metastasis unless they are deemed to be non-progressive, asymptomatic and off corticosteroid therapy for at least four weeks, as per investigator's assessment;
- Active malignancy other than prostate cancer;
- Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception;
- Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct;
- Known hypersensitivity to 177Lu-PSMA-617 or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Actividad personalizada
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6 cycles of personalized activity (1st cycle based on BSA and eGFR; cycles 2-6 based on renal dosimetry), maximum 22.2 GBq, every 6 weeks 6 cycles of 7.4 GBq every 6 weeks |
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Comparador activo: Actividad fija
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6 cycles of personalized activity (1st cycle based on BSA and eGFR; cycles 2-6 based on renal dosimetry), maximum 22.2 GBq, every 6 weeks 6 cycles of 7.4 GBq every 6 weeks |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Administered activity of 177Lu-PSMA-617
Periodo de tiempo: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
In GBq, cumulative and average per cycle. |
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
|
Number of participants with subacute adverse events of special interest (AESIs)
Periodo de tiempo: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
Subacute AESIs are:
|
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Variación de puntaje en el cuestionario Euroqol-5 Dimension-5 Nivel (EQ-5D-5L) al inicio
Periodo de tiempo: Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
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Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
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|
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Variación de puntaje en la evaluación funcional de la terapia contra el cáncer - cuestionario de próstata (FACT -P) al inicio
Periodo de tiempo: Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
|
|
Variación de puntaje en el cuestionario de inventario de dolor breve (BPI-SF) al inicio
Periodo de tiempo: Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
|
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Variación de puntaje en el cuestionario multidisciplinario de la Sociedad de la Glándula Salival (MSGS) al inicio
Periodo de tiempo: Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
Al inicio, a las 18 semanas y al final del tratamiento (cada ciclo es de 6 semanas, hasta 6 ciclos consecutivos)
|
|
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Best biochemical response
Periodo de tiempo: From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest
|
Maximum percent decrease of serum prostate-specific antigen (PSA) after first administration. |
From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest
|
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PSA progression-free survival (PSA-PFS)
Periodo de tiempo: From date of first administration until the date of PSA progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
Time from first administration to an increase in PSA greater than 25%, and greater than 2 ng/ml, above nadir, confirmed at least 3 weeks later. |
From date of first administration until the date of PSA progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
|
Radiological progression-free survival (rPFS)
Periodo de tiempo: From date of first administration until the date of radiological progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
Time from first administration to the date of radiographic disease progression based on RECIST 1.1/PCWG3. |
From date of first administration until the date of radiological progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
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Investigator-assessed overall PFS
Periodo de tiempo: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
Time from first administration to the earliest of clinical (worsening of a patient's clinical status attributed to disease progression), biochemical or radiological progression considering all data (scheduled and unscheduled) available to the investigator. |
From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
|
Time to first symptomatic skeletal event (SSE)
Periodo de tiempo: From date of first administration until the date of first SSE or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
Time to first Symptomatic Skeletal Event (SSE) is defined as the time from first administration to the date of the SSE. The SSE date is the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first. |
From date of first administration until the date of first SSE or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
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Overall survival (OS)
Periodo de tiempo: From date of first administration until the date of death, assessed over a minimum of 60 months
|
Overall Survival (OS) is defined as the time from the date of the first administration to the date of death due to any cause. |
From date of first administration until the date of death, assessed over a minimum of 60 months
|
|
Metabolic response on FDG-PET/CT
Periodo de tiempo: At baseline and at 12 weeks
|
Metabolic response is defined as complete metabolic response (CMR, disappearance of all lesions on FDG PET), partial metabolic response (PMR, decrease of uptake by ≥30%), stable metabolic disease (SMD, variation of FDG uptake by <30%), progressive metabolic disease (PMD, increase of FDG uptake by ≥30%) |
At baseline and at 12 weeks
|
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Molecular response on PSMA-PET/CT
Periodo de tiempo: At baseline and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)
|
Molecular response is defined as the variation of molecular tumor volume (MTV) on PSMA-PET/CT |
At baseline and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)
|
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Best molecular response on quantitative 177Lu SPECT/CT during treatment
Periodo de tiempo: From first cycle's Day 3 until the last cycle's Day 3 (each cycle is 6 weeks, up to 6 consecutive cycles)
|
Best molecular response is defined as the maximum percent decrease of molecular tumor volume (MTV) at any time after post-treatment quantitative 177Lu SPECT/CT performed on the first cycle's Day 3, up to the post-treatment quantitative 177Lu SPECT/CT performed on the last cycle's Day 3 |
From first cycle's Day 3 until the last cycle's Day 3 (each cycle is 6 weeks, up to 6 consecutive cycles)
|
|
Number of participants with any adverse events (AEs)
Periodo de tiempo: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
All adverse events that occur from the first administration of 177Lu-PSMA-617 until 6 weeks after the last administration of 177Lu-PSMA-617 or prior to the initiation of subsequent anticancer treatment. |
From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)
|
|
Number of participants with laboratory adverse events (AEs)
Periodo de tiempo: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
Adverse events seen on laboratory (hematology, biochemistry) that occur from the first administration of 177Lu-PSMA-617 until progression or until the initiation of subsequent anticancer treatment if earlier. |
From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months
|
|
Number of participants with delayed adverse events of special interest (AESIs)
Periodo de tiempo: From date of first administration until the date of death, assessed over a minimum of 60 months
|
Delayed AESIs (renal impairment and secondary hematological malignancies) that occur from the first administration of 177Lu-PSMA-617 until death (or study termination) |
From date of first administration until the date of death, assessed over a minimum of 60 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Jean-Mathieu Beauregard, MD, CHU de Québec-Université Laval
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2025-7829
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
There is an intent to create an imaging and data bank from this study.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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