E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-Resistant Prostate Cancer |
Cáncer de próstata metastásico resistente a la castración |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Castration-Resistant Prostate Cancer |
Cáncer de próstata metastásico resistente a la castración |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Evaluate objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 assessed by Blinded Independent Central Review (BICR) in subjects with mCRPC and measurable disease at baseline. - Assess Radiographic Progression Free Survival (rPFS) assessed by BICR in all treated subjects with mCRPC using RECIST V1.1 for soft tissue disease progression and PCWG2 for bone disease progression. |
- Evaluar la tasa de respuestas objetivas (TRO) mediante los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST) v1.1, evaluados mediante revisión central independiente enmascarada (RCIE) en pacientes con CPRCm y enfermedad medible en el momento basal. - Evaluar la supervivencia libre de progresión radiográfica (SLPr) evaluada mediante RCIE en todos los pacientes tratados con CPRCm usando los RECIST v1.1 en cuanto a progresión de la enfermedad en partes blandas y los PCWG2 en cuanto a progresión de la enfermedad en hueso. |
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E.2.2 | Secondary objectives of the trial |
- Assess radiographic/clinical Progression Free Survival (rcPFS) - Assess overall survival (OS). - Evaluate PSA response rate (PSA-RR) - Determine the safety and tolerability in all treated subjects . - Estimate changes in pain as measured by the Brief Pain Inventory-Short Form (BPI-SF) - Estimate changes in cancer-related symptoms and quality of life (QoL) using the FACT-P questionnaire - Estimate changes in health status and health utility as measured by the 3-level EQ-5D-3L questionnaire |
- Evaluar la supervivencia libre de progresión radiográfica/clínica (SLPrc). - Evaluar la supervivencia global (SG). - Evaluar la tasa de respuesta en PSA (TR-PSA) - Determinar la seguridad y la tolerabilidad en todos los pacientes tratados. - Estimar los cambios en el dolor medido por el Inventario Breve del Dolor – Formulario Corto (BPI-SF) - Estimar los cambios en los síntomas relacionados con el cáncer y la calidad de vida (CdV) usando el cuestionario FACT-P - Estimar los cambios en el estado de salud y la utilidad de salud medidos por el cuestionario EuroQol Cinco dimensiones con 3 niveles (EQ-5D-3L) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men, 18 years or older with histologic confirmation of adenocarcinoma of the prostate and evidence of Stage IV disease (defined by AJCC) -ECOG performance status 0-1 -Ongoing androgen deprivation therapy (ADT) with a GnRH analogue or a surgical/medical castration with testosterone level of ≤1.73nmol/L (50ng/dL) -Patients with skeletal system symptoms who are already on medications to strengthen bones are allowed if they were started ˃28 days before enrollment -Bone-directed radiotherapy to pelvic region for ease of pain from painful bone metastases is allowed up to 14 days before -Sufficient fresh or archival tumor tissue obtained within 5 years prior to enrollment from a metastatic tumor lesion or from a primary tumor lesion that has not been previously irradiated (formalin-fixed paraffin-embedded [FFPE] block or unstained tumor tissue sections). |
- Varones, de 18 años o más con confirmación histológica de adenocarcinoma de la próstata y pruebas de enfermedad en estadio IV (tal como se define según los criterios del American Joint Committee on Cancer (AJCC) - PS 0-1 del ECOG - Tratamiento de privación androgénica (TPA) mantenido con un análogo de la hormona liberadora de gonadotropina (GnRH) o castración quirúrgica o médica con un nivel de testosterona ≤ 1,73 nmol/l (50 ng/dl) - Se permiten pacientes con síntomas del sistema esquelético que ya están tomando medicamentos para fortalecer los huesos si se iniciaron >28 días antes de la inclusión en el estudio - Se permite la radioterapia dirigida al hueso para la región pélvica para aliviar el dolor de las metástasis óseas dolorosas hasta 14 días antes del comienzo del tratamiento - Suficiente tejido tumoral nuevo o de archivo obtenido en el plazo de 5 años antes del reclutamiento, de una lesión tumoral metastásica o de una lesión del tumor primario que no se haya irradiado previamente (bloque fijado en formol e incluido en parafina [FFIP] o cortes de tejido tumoral no teñido). |
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E.4 | Principal exclusion criteria |
-Cancer that has spread to the liver or brain -Active, known, or suspected autoimmune disease or infection -Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors) |
- Cáncer que se ha extendido al hígado o al cerebro - Enfermedad autoinmune o infección activa, conocida o de sospecha - Tratamiento previo con cualquier fármaco dirigido a las vías de co-estimulación de las células T (como los inhibidores de las vías del punto de control) |
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E.5 End points |
E.5.1 | Primary end point(s) |
1/Objective Response Rate (ORR) 2/Radiographic Progression-Free Survival (rPFS) |
1/ Tasa de respuestas objetivas (TRO) 2/ Supervivencia libre de progresión radiográfica (SLPr) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1/ Approximately 24 weeks from treatment initiation 2/ Approximately 12 months from treatment initiation |
1/ Aproximadamente 24 semanas desde el inicio del tratamiento 2/ Aproximadamente 12 meses desde el inicio del tratamiento |
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E.5.2 | Secondary end point(s) |
1/Radiographic/Clinical Progression-Free Survival (rcPFS) by BICR 2/Overall Survival (OS) and PSA response rate (PSA-RR) 3/Safety and Tolerability |
1/ Supervivencia libre de progresión radiográfica/clínica (SLPrc) mediante RCIE 2/ Supervivencia global (SG) y tasa de respuesta en PSA (TR-PSA) 3/ Seguridad y tolerabilidad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ Approximately 12 months from treatment initiation 2/ Up to 5 years from treatment initiation 3/ Approximately 12 months from treatment initiation |
1/ Aproximadamente 12 meses desde el inicio del tratamiento 2/ Hasta 5 años desde el inicio del tratamiento 3/ Aproximadamente 12 meses desde el inicio del tratamiento |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Assessments, Biomarker Assessments, Outcomes Research Assessments |
Evaluaciones de inmunogenicidad, evaluaciones de biomarcadores, evaluaciones de investigación de resultados |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Canada |
Denmark |
France |
Germany |
Italy |
Poland |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last follow-up visit of the last patient |
Última visita de seguimiento del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 9 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 5 |