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Neu Direction: Testing the Efficacy of Adding HER Inhibition to Standard of Care in Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer

22 de julio de 2026 actualizado por: Asona Juwan Lui, University of California, San Diego

Neu Direction: A Single Center Phase II Randomized Clinical Trial to Assess the Efficacy of Adding HER Inhibition to Standard of Care in Patients With Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer

The goal of this clinical trial is to learn if neratinib, an FDA-approved oral pan-HER2/3/4 inhibitor, improves disease control for participants with metastatic endocrine-resistant ER+/HER2-negative breast cancer. Neratinib is already approved for the treatment of HER2-postive breast cancers. The study will also learn about the safety of adding this drug to standard of care treatments. The main questions it aims to answer are:

  1. Does adding neratinib to standard of care systemic therapy improve disease control for patients with metastatic hormone-driven breast cancer that is resistant to endocrine therapy?
  2. What side effects do participants have when adding neratinib to standard of care therapy? Researchers will compare standard of care endocrine therapy regimens with and without neratinib to see if neratinib improves control of treatment-resistant metastatic breast cancer that has continued to progress while eon first line endocrine therapy.

Participants will:

  1. Take standard of care endocrine therapy for metastatic endocrine-resistant breast cancer as determined by their medical oncologist or standard of care therapy with neratinib daily
  2. Visit the clinic every 3 months for checkups, tests and imaging studies

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

This is a prospective 2-arm Phase II study testing the efficacy of adding neratinib to standard of care therapy in patients with MLH1-low ER+/HER2- endocrine-resistant breast cancer . Patients with endocrine-resistant ER+/HER2- breast cancer who have lesions visible on CT scan will be recruited as they are seen in breast medical oncology and radiation oncology clinics at UC San Diego Health. Patients will be eligible if they have measurable persistent, recurrent, progressive or metastatic disease on imaging (including FDG PET scan) while on endocrine therapy. At least one lesion must be biopsied and confirmed ER+ by immunohistochemistry and HER2- within 6 months of study screening. Genomic mutation profile will be analyzed along with trial results to identify other potential mutations associated with MLH1 expression and/or neratinib response. Participants will be stratified by nuclear MLH1 expression on their biopsy tissue using immunohistochemistry. MLH1negative (nuclear MLH1 detectable in <5% of tumor cells) and MLH1-low patients (<50% tumor cells positive) hereafter grouped as "MLH1-low" will be randomized to standard of care without (75 participants) or with (75 participants) the addition of neratinib in Arm 1 and Arm 2 respectively . Standard of care therapy can include any endocrine therapy with or without CDK4/6 inhibitors. Prior exposure to CDK4/6 inhibitors is acceptable but not prior HER2-targeted therapy. Neratinib will be administered with a standard ramp up to therapeutic dose to minimize side effects with 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter. Treatment response will be monitored via imaging every 3 months while on study and measured using RECIST v. 1.1 criteria and/or mPERCIST criteria as appropriate using FDG-PET. Participants will remain on study until cessation due to side effects or disease progression. Biopsy at disease progression will be encouraged but not required.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

150

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Asona Lui, MD, PhD
  • Número de teléfono: 858-822-4319
  • Correo electrónico: ajlui@health.ucsd.edu

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

  • Estados Unidos
    • California
      • La Jolla, California, Estados Unidos, 92037
        • UC San Diego Health Moores Cancer Center
        • Contacto:
        • Investigador principal:
          • Asona Lui, MD, PhD
        • Sub-Investigador:
          • Alyssa Beck, MD
        • Sub-Investigador:
          • Svasti Haricharan, PhD

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

Inclusion Criteria:

  1. Female over the age of 18 at the time of study enrollment
  2. Not pregnant, planning to become pregnant or breast feeding
  3. Metastatic ER+/HER2- breast cancer that has progressed on 1st line therapy including endocrine therapy +/- CDK4/6 inhibitors
  4. At least one metastatic lesion visible on imaging (including FDG-PET)
  5. At least one metastatic lesion must be biopsied and confirmed ER+ and HER2- by immunohistochemistry within 6 months of study screening (HER2 equivocal disease will be confirmed HER2- by FISH)
  6. Tumors must be MLH1-low defined by <50% tumor cells positive for nuclear MLH1 expression on immunohistochemistry
  7. Standard of care next line endocrine therapy can include any endocrine therapy
  8. Performance status ECOG > 3
  9. Life expectancy > 1 year
  10. Ability to get serial imaging studies

Exclusion Criteria:

  1. History of concurrent use of other HER2-targeted therapy
  2. Concurrent use of other targeted systemic therapy
  3. History of other cancers other than non-melanoma skin cancer
  4. Actionable mutations on tumor genomic sequencing will be ineligible, and those participants encouraged to proceed with the relevant targeted therapy
  5. Participants where there is not at least one imaging apparent lesion that has not been treated with prior targeted therapy (for example palliative radiation or cryoablation)
  6. Contraindications to Neratinib use including allergy or hypersensitivity
  7. Baseline grade 3+ diarrhea

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Único

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Standard of Care
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor
Droga: Endocrine therapy may include one of the following therapies: letrozole, anastrozole, exemestane, tamoxifen or fulvestrant
Endocrine therapy with out without CDK4/6 inhibitor
Droga: CDK4/6 + Endocrine therapy
Endocrine therapy with or without CDK 4/6 inhibitor
Experimental: Stanard of Care + Neratinib
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor + Neratinib
Droga: CDK4/6 + Endocrine therapy
Endocrine therapy with or without CDK 4/6 inhibitor
Droga: Neratinib + endocrine therapy
Neratinib 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter
Otros nombres:
  • neratinib

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Median Progression-Free Survival
Periodo de tiempo: From enrollment through study completion, an average of 1 year.
From enrollment through study completion, an average of 1 year.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Periodo de tiempo: From enrollment through study completion, an average of 1 year.
Adverse events will be quantified using the CTCAE v4.0 every 3 months
From enrollment through study completion, an average of 1 year.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

University of California, San Diego

Investigadores

  • Investigador principal: Asona Lui, MD, PhD, UC San Diego

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de julio de 2027

Finalización primaria (Estimado)

1 de mayo de 2032

Finalización del estudio (Estimado)

1 de junio de 2035

Fechas de registro del estudio

Enviado por primera vez

14 de julio de 2026

Primero enviado que cumplió con los criterios de control de calidad

22 de julio de 2026

Publicado por primera vez (Actual)

27 de julio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

27 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

22 de julio de 2026

Última verificación

1 de julio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • BC250474 (Otro número de subvención/financiamiento: Congressionally Designated Medical Research Program (CDMRP), US ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY)
  • 813310 (Otro identificador: UC San Diego Institutional Review Board (IRB))

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

Only IPD used in the results publication

Marco de tiempo para compartir IPD

Beginning 6 months and ending 3 years after publication of results

Criterios de acceso compartido de IPD

Proposal that describes planned analyses must be submitted and approved by the Principle Investigator, Asona Lui and data sharing agreement must be signed with the requesters institution. Evidence of IRB approval must be provided by the requestor prior to the sharing of any data.

Tipo de información de apoyo para compartir IPD

  • PROTOCOLO DE ESTUDIO
  • SAVIA
  • CIF

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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