Resumen

El objetivo principal del estudio es medir la eficacia de saruparib (AZD5305) más camizestrant en comparación con el inhibidor de CDK4/6 a elección del médico más terapia endocrina (ET) en pacientes con cáncer de mama avanzado con mutación en BRCA1, BRCA2 o PALB2 (PALB2m), receptores hormonales positivos y HER2 negativo (definido como IHC 0, 1+, 2+/ ISH no amplificado).

Descripción detallada

Aproximadamente 2.620 participantes serán seleccionados para alcanzar aproximadamente 500 participantes aleatorizados a la intervención del estudio. Los participantes serán aleatorizados en una proporción 2:2:1 a uno de los siguientes grupos de intervención: * Brazo 1: saruparib (AZD5305) más camizestrant * Brazo 2: inhibidor de CDK4/6 a elección del médico más ET a elección del médico * Brazo 3: inhibidor de CDK4/6 a elección del médico más camizestrant El tratamiento continúa hasta la progresión de la enfermedad confirmada por BICR, la aparición de toxicidad inaceptable o la retirada del consentimiento por parte del participante.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Adult females, pre/peri-menopausal and/or post-menopausal, and adult males
Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer
Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease
ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks
FFPE tumour tissue from each participant
Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2
Adequate organ and marrow function

Criterios de exclusión

Participants with history of MDS/AML or with features suggestive of MDS/AML
Participants with any known predisposition to bleeding
Any history of persisting severe cytopenia
Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections
Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection
History of another primary malignancy
Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia
Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease
Evidence of active and uncontrolled hepatitis B and/or hepatitis C
Evidence of active and uncontrolled HIV infection
Active tuberculosis infection
Cardiac criteria, including history of arrythmia and cardiovascular disease
Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions
Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment
Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET up to 28 days before randomisation
Prior treatment within 28 days with blood product support or growth factor support
Any systemic concurrent anti-cancer treatment
Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation:
Strong and moderate CYP3A4 inducers/inhibitors
Sensitive CYP2B6 substrates
Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
Concomitant use of drugs that are known to prolong QT and have a known risk of TdP
Systemic use of atropine
Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.

San Miguel de Tucumán, Argentina

WITHDRAWN

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Saruparib (AZD5305)

Camizestrant

Abemaciclib

Ribociclib

Palbociclib

Fulvestrant

Letrozole

Anastrozole

Exemestane

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores

Contactos

AstraZeneca Clinical Study Information Center