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 |
Prostate cancer |
Cáncer de próstata |
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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 | 19.1 |
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 | 19.1 |
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 |
To determine the efficacy (as assessed by rPFS) of olaparib versus investigator choice of enzalutamide or abiraterone acetate in men with mCRPC with BRCA1, BRCA2 or ATM qualifying mutations (Cohort A) |
Determinar la eficacia (evaluada SLPr) del olaparib frente al fármaco de elección del investigador (enzalutamida o acetato de abiraterona) en pacientes con CPMRC con las mutaciones calificadoras BRCA1, BRCA2 o ATM (Cohorte A) |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of olaparib versus investigator choice of enzalutamide or abiraterone acetate in subjects with HRR qualifying gene mutations measured by objective response rate in Cohort A, rPFS in Cohort A+B, time to pain progression in Cohort A and overall survival in Cohort A |
Determinar la eficacia del olaparib frente al fármaco de elección del investigador (enzalutamida o acetato de abiraterona) en pacientes con mutaciones genéticas calificadoras HRR evaluada mediante la tasa de respuesta objetiva en la Cohorte A, SLPr en la Cohorte A+B, tiempo hasta la progresión del dolor en la Cohorte A y supervivencia global en la Cohorte A |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis of prostate cancer. 2. Candidate for treatment with enzalutamide or abiraterone with documented evidence of mCRPC. 3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC. 4. Ongoing therapy with LHRH analog or bilateral orchiectomy. 5. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy). 6. Qualifying HRR mutation in tumor tissue by the Lynparza HRR Assay |
1. Diagnóstico histologico confirmado de cáncer de prostata. 2. Candidatos para el tratamiento con enzalutamida or abiraterona con evidencia documentada de CPMRC. 3. Sujetos que han progresado con el tratamiento previo de un nuevo agente hormonal (e.j. abiraterona acetato y/o enzalutamida) para el tratamiento de CPMRC. 4. Tratamiento en curso con análogos LHRH u orquiectomía bilateral. 5. Progresión radiológica en el momento de entrada al estudio mientras que en la terapia de privación de andrógenos (o despues de una orquiectomía bilateral). 6. HRR mutación cualificadora en un tumor (téjido) por el análisis HRR de Lynparza. |
|
E.4 | Principal exclusion criteria |
1. Any previous treatment with PARP inhibitor, including olaparib 2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy. 3. Other malignancy (including MDS and MGUS) within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥5 years. 4. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML. 5. *Subjects with known brain metastases. |
1. Cualquier tratamiento anterior con inhibidores de PARP, incluyendo olaparib 2. Sujetos que presenten cualquier tratamiento previo con quimioterapia citotóxica lesiva del ADN. 3. Otros tumores malignos (incluyendo MDS y MGUS) dentro de los últimos 5 años exceptuando: cáncer de piel no-melanoma tratado adecuadamente u otros tumores sólidos tratados adecuadamente sin evidencia de la enfermadad durante ≥5 años. 4. Sujetos con síndrome mielodisplásico o leucemia mieloide aguda o con características de MDS/AML. 5. *Sujetos con metástasis cerebral conocida. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Radiological progression free survival (rPFS) by blinded independent central review (BICR) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria |
Supervivencia libre de progresión radiológica (SLPr) según revisión central independiente y enmascarada (RCIE) usando los criterios RECIST 1.1 (tejidos blandos) y PCWG3 (hueso) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria |
Al inicio y cada 8 semanas (±7 días), en relación con la fecha de aleatorización, hasta progresión radiólogica objetiva de la enfermedad según RCIE usando los criterios RECIST 1.1 (tejidos blandos) y PCWG3 (hueso) |
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E.5.2 | Secondary end point(s) |
Confirmed ORR by BICR assessment in subjects with measurable disease using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria
rPFS by BICR using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria
Pain progression based on BPI-SF item 3 “worst pain in 24 hours” and opiate analgesic use (AQA score)
Overall survival |
•TRO confirmada según RCIE en pacientes con enfermedad medible según criterios RECIST 1.1 (tejidos blandos) y PCWG3 (hueso)
•SLPr según RCIE usando criterios RECIST 1.1 (tejidos blandos) y PCWG3 (hueso)
•Progresión del dolor según el apartado 3 del Brief Pain Inventorio-Short Form (BPI-SF) “peor dolor en 24 horas” y el uso de analgésicos opiáceos (puntuación del Algoritmo de Cuantificacion de Analgésico) (AQA)
•Supervivencia Global (SG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and every 8 weeks (± 7 days), relative to the date of randomization, until objective radiological disease progression by BICR
Subjects will complete the BPI-SF daily on the ePRO device for the 7 days just prior to day 1 baseline visit and every 4 weeks
The status of ongoing, withdrawn (from the study) and “lost to follow-up” subjects at the time of an overall survival analysis should be obtained by the site personnel by checking the subject notes, hospital records, contacting the subject’s general practitioner and checking publicly available death registries. |
Al inicio y cada 8 semanas (±7 días), en relación con la fecha de aleatorización, hasta progresión radiólogica objetiva de la enfermedad según RCIE usando los criterios RECIST 1.1 (tejidos blandos) y PCWG3 (hueso)
Pacientes que completarán el BPI-SF diariamente en el dispositivo ePRO durante los 7 días anteriores al día 1 de inicio de visita y cada 4 semanas
El personal del centro debe obtener el estado de los sujetos en curso, retirados (del estudio) y "perdidos con el seguimiento" en el momento de realizar un análisis de supervivencia general, comprobando las notas de los sujetos, los registros hospitalarios, contactando al facultativo general de los sujetos y verifcando los registros de defunción disponibles públicamente. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 190 |
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 |
Argentina |
Australia |
Austria |
Brazil |
Canada |
China |
Denmark |
France |
Germany |
Israel |
Japan |
Korea, Republic of |
Netherlands |
Norway |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of this study is defined as ‘the last visit of the last subject undergoing the study". |
El final del estudio se define como "la última visita del último sujeto que participe en el estudio" |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |