Resumen

El objetivo del estudio es demostrar la superioridad de saruparib (AZD5305) en relación con el placebo añadido a un régimen estándar de radioterapia (RT) + terapia de privación androgénica (TPA), mediante la evaluación de la supervivencia libre de metástasis en participantes con cáncer de próstata localizado/localmente avanzado de alto riesgo y muy alto riesgo con mutación en el gen de cáncer de mama (BRCAm).

Descripción detallada

Aproximadamente 700 participantes adultos con cáncer de próstata localizado/localmente avanzado serán aleatorizados en una proporción 1:1 para recibir saruparib o placebo con TPA (+ abiraterona) en una de las dos cohortes siguientes: Cohorte A: 400 participantes adultos con cáncer de próstata de reciente diagnóstico de alto riesgo y muy alto riesgo (localizado/localmente avanzado) que hayan recibido RT primaria y estén bajo TPA continua, y participantes con recaída bioquímica de alto riesgo (RB) [incluida la persistencia del antígeno prostático específico (PSA)] tras prostatectomía radical que hayan recibido RT de rescate y estén bajo TPA continua. Cohorte B: 300 participantes adultos con cáncer de próstata de reciente diagnóstico de muy alto riesgo (localmente avanzado) que hayan recibido RT primaria y estén bajo TPA continua y abiraterona. Todos los participantes serán seguidos para supervivencia hasta el final del estudio. Se convocará un comité de monitoreo de datos (CMD) independiente, compuesto por expertos, para confirmar la seguridad y eficacia de saruparib + TPA (+ abiraterona).

Elegibilidad

Edad mínima: 18 YearsSexo: MALE

Criterios de inclusión

Male participants with a histologically documented diagnosis of prostate adenocarcinoma.
Newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer or a high-risk biochemical recurrence (BCR) following radical prostatectomy.
Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample.
Confirmed BRCA1 or BRCA2 mutation status by central tumour tissue is required for enrolment.
Participants required to have a computed tomography (CT) or magnetic resonance imaging (MRI) and a bone scan following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
Participants required to have a prostate-specific membrane antigen-positron emission tomography (PSMA-PET) following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomization.
Minimum life expectancy of 12 months.
Adequate organ and bone marrow function as described in study protocol.
All participants will have received either primary or salvage RT. Participants must be eligible for randomisation within 10 months of initial diagnosis (de novo or BCR). Radiotherapy administered to the prostate (± pelvis) either in the primary or salvage setting must be delivered with curative intent. Use of metastases-directed therapy, as part of the RT radiation plan, is permitted as localised RT treatment for a metastatic lesion(s) outside the pelvis.
All participants will have received a planned regimen of ADT with a gonadotropin releasing hormone (GnRH) analogue.
Participants must not father children or donate sperm from signing informed consent form (ICF), during the study intervention and for 6 months after the last dose of study intervention.
Participants must use a condom (with spermicide - where permitted) from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.

Criterios de exclusión

Participants with a history of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
Participants with any known predisposition to bleeding \[e.g., active peptic ulceration, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy\].
Any history of persisting (\> 2 weeks) severe cytopenia due to any cause.
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or abiraterone.
History of another primary malignancy, with exceptions.
Persistent toxicities \[Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2\] caused by previous anticancer therapy.
Cardiac criteria, including history of arrhythmia and cardiovascular disease.
Evidence of active and uncontrolled hepatitis B and/or hepatitis C.
Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection.
Active tuberculosis infection.
Any prior chemotherapy (i.e., docetaxel) or immunotherapy; any prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor.
Prior treatment within 14 days with blood product support or growth factor support.
Concomitant use of strong inducers and inhibitors of CYP3A4 (applies to saruparib and abiraterone) or herbal supplements within 21 days or at least 5 half-lives (whichever is longer), of randomization.
Concomitant use of drugs that are known to prolong QT and have a known risk of Torsades de Pointes (TdP).
Participants with a known hypersensitivity to saruparib or any excipients of these products.

Viedma, Argentina

NOT_YET_RECRUITING

Estudio de Fase III, Aleatorizado, Doble Ciego, Controlado con Placebo de Saruparib (AZD5305) Adyuvante en Pacientes con Cáncer de Próstata Localizado de Alto Riesgo con Mutación en BRCA que Reciben Radioterapia con Privación Androgénica (EvoPAR-Prostate02)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Saruparib

Placebo

Abiraterone + Prednisolone/Prednisone

Androgen Deprivation Therapy (ADT)

Ubicaciones

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Patrocinadores

Contactos

AstraZeneca Clinical Study Information Center