- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07599137
Abemaciclib Dose Escalation in Early High-Risk Breast Cancer Adjuvant Therapy (ADES)
Study on the Safety and Efficacy of Abemaciclib Dose Escalation Strategy in Adjuvant Therapy for Early High-Risk Breast Cancer
Abemaciclib combined with endocrine therapy has become one of the important adjuvant treatment regimens for patients with HR+/HER2- high-risk early breast cancer. However, adverse events such as diarrhea, fatigue, neutropenia and elevated liver enzymes are concentrated in the early stage of adjuvant therapy, which often lead to dose reduction, temporary drug interruption or even permanent discontinuation. This further affects treatment adherence, relative dose intensity (RDI) and treatment completion rate.
Findings from the TRADE study suggest that a step-up dosing strategy, initiating at a lower dose followed by gradual titration to the standard dose, combined with standardized patient education and symptomatic management, may improve early treatment tolerance, reduce the burden of partial toxicities, and increase the likelihood of patients achieving and maintaining abemaciclib 150 mg twice daily. Based on the above evidence and clinical experience, step-up dosing has been adopted by some clinicians for real-world clinical practice.
Nevertheless, existing evidence is mainly derived from non-Chinese populations. There is still a lack of systematic real-world data on step-up dosing among Chinese breast cancer patients under routine outpatient management, including the early toxicity profile, dose escalation achievement rate at each stage, dose adjustment pathways (prolonged escalation, treatment pause or dose de-escalation), RDI distribution, correlation with quality of life, and baseline factors affecting treatment tolerance and dose target attainment. Therefore, it is necessary to conduct a real-world study focused on Chinese patients to fill the gap in local clinical evidence, and provide a basis for clinical pathway formulation, patient education, and subsequent multicenter validation studies.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Lize Wang, Doctor
- Número de teléfono: +86-010-88197830
- Correo electrónico: lize2010@163.com
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Aged ≥18 years;
- Pathologically confirmed breast cancer with ER and/or PR positive, HER2 negative;
- Completed radical mastectomy/radiacal breast surgery;
- Plan to receive abemaciclib combined endocrine therapy for at least 12 weeks, with abemaciclib administered via a step-up dosing regimen;
- ECOG performance status 0-1;
- Adequate organ function meeting medication requirements (routine blood test, liver and renal function, and other indicators consistent with clinical medication safety criteria);
- Signed written informed consent.
Exclusion Criteria:
- Previous exposure to any CDK4/6 inhibitor;
- Active infection or severe infection requiring systemic anti-infective treatment;
- Significant gastrointestinal diseases such as chronic diarrhea, inflammatory bowel disease, short bowel syndrome, which may affect drug absorption or increase the risk of diarrhea;
- Significant baseline hepatic or renal dysfunction, or uncontrolled severe comorbidities judged by the investigator to affect safety or treatment adherence;
- Pregnancy or lactation;
- Any other condition deemed ineligible for enrollment by the investigator.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Dose escalation group
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
|
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Rate of inadequate dosing
Periodo de tiempo: From enrollment to the end of treatment at 12 weeks
|
Proportion of patients with inadequate dosing from postoperative treatment initiation to week 12
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From enrollment to the end of treatment at 12 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Dose Target Attainment and Treatment Intensity
Periodo de tiempo: From enrollment to the end of treatment at 12 weeks"
|
Proportion of patients achieving 150 mg BID at Week 12.
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From enrollment to the end of treatment at 12 weeks"
|
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QoL deterioration rate
Periodo de tiempo: From enrollment to the end of treatment at 12 weeks.
|
Proportion of patients experiencing a deterioration in health-related quality of life defined as a decrease of ≥10 points from baseline through EORTC QLQ-C30.
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From enrollment to the end of treatment at 12 weeks.
|
Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortes J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. doi: 10.1200/JCO.20.02514. Epub 2020 Sep 20.
- Mayer EL, Trapani D, Kim SE, Faggen M, Sinclair N, Sanz-Altamira P, Battelli C, Berwick S, Lo S, Acevedo J, Sinclair S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM. TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer. Ann Oncol. 2026 Jan;37(1):117-124. doi: 10.1016/j.annonc.2025.09.141. Epub 2025 Oct 17.
- Goetz MP, Cicin I, Testa L, Tolaney SM, Huober J, Guarneri V, Johnston SRD, Martin M, Rastogi P, Harbeck N, Shahir A, Wei R, Andre V, Rugo HS, O'Shaughnessy J. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer. 2024 Apr 26;10(1):34. doi: 10.1038/s41523-024-00639-1.
- Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, Andre V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. doi: 10.1016/S1470-2045(22)00694-5. Epub 2022 Dec 6.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- BC-P40
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
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.
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