Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer (NeoEribulin)
31 de octubre de 2017 actualizado por: SOLTI Breast Cancer Research Group
A Phase II, Open-label, Single-arm, Exploratory Pharmacogenomic Study of Single Agent Eribulin (HALAVEN®) as Neoadjuvant Treatment for Operable Stage I-II HER2 Non-overexpressing Breast Cancer.
This is a prospective, non-randomized, open-label, multicenter, single-arm exploratory pharmacogenomic study of single agent eribulin as neoadjuvant therapy in patients with operable Stage III HER2 non-overexpressing breast cancer.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
163
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.
Ubicaciones de estudio
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Deggendorf, Alemania, 94469
- Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum
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Köln, Alemania, 51067
- Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.
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Munic, Alemania, 81377
- Brustzentrum der Universität München
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Rostock, Alemania, 18059
- Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik
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Barcelona, España, 08025
- Hospital de la Santa Creu i Sant Pau
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Barcelona, España
- Hospital Universitario Vall d´Hebrón
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Barcelona, España, 08035
- Hospital Universitario Vall d´Hebrón
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Castelló de la Plana, España, 12002
- Complejo Hospitalario de Castellón
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Cáceres, España, 10003
- Complejo Hospitalario San Pedro de Alcántara
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Córdoba, España, 14004
- Hospital Universitario Reina Sofia
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Denia, España, 03700
- Hospital Marina Salud de Denia
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Jaén, España, 23007
- Complejo Hospitalario de Jaen
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Lleida, España, 25198
- Hospital Universitari Arnau de Vilanova de Lleida
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Madrid, España, 28034
- Hospital Universitario Ramón y Cajal
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Madrid, España, 28041
- Hospital Universitario 12 de Octubre
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Madrid, España, 28040
- Hospital Universitario Clínico San Carlos
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Madrid, España, 28222
- Hospital Universitario Puerta de Hierro de Majadahonda
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Murcia, España, 30120
- Hospital Universitario Virgen de La Arrixaca
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Reus, España, 43201
- Hospital Universitari Sant Joan de Reus
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Santiago de Compostela, España, 15706
- Complejo Hospitalario Universitario de Santiago
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Sevilla, España, 41013
- Hospital Universitario Virgen del Rocio
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Sevilla, España, 41007
- Hospital Virgen de la Macarena
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Torrevieja, España, 03186
- Hospital de Torrevieja
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Valencia, España, 46010
- Hospital Clínico Universitario de Valencia
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Valencia, España, 46015
- Hospital Arnau de Vilanova de Valencia
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Zaragoza, España, 50009
- Hospital Universitario Lozano Blesa
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Villejuif, Francia, 94800
- Institut Gustave Roussy
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Coimbra, Portugal, 3001-651
- Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE
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Lisboa, Portugal, 1500-650
- Hospital da Luz
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Porto, Portugal, 4200-072
- Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
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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
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Written informed consent, specifically highlighting the molecular characterization of tumor and genomic samples
- Age ≥18 years
Histologically confirmed invasive breast carcinoma, with all of the following characteristics:
- Primary tumor ≥2cm in largest diameter (cT1-3)
- cN0-1
- No evidence of distant metastasis (M0)
- Breast cancer (BC) eligible for primary surgery
- Available pre-treatment core (Tru-cut) biopsy or possibility of performing one
HER2-negative BC (as per local assessment), defined as either of the following:
- 0-1+ expression by IHC
- 2+ expression by IHC and in situ hybridization (FISH/CISH) without HER2 gene amplification (<4 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to Cr17 signals] of <1.8)
- Is situ hybridization (FISH/CISH) without HER2 gene amplification, independently of IHC
- Known hormone receptor (ER/PgR) status (as per local assessment) or the possibility of performing the tests
- Known percentage of hormone receptor (ER/PgR) and Ki67-positive tumor cells (as per local assessment), or possibility of performing the tests
- In the case of a multifocal tumor, the largest lesion must be ≥2 cm and designated the "target" lesion for all subsequent tumor evaluations and HER2-negative status must be documented in all the tumor foci
- ECOG performance status of 0 or 1
Laboratory values as follows:
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Platelets count ≥100 x 109/L
- Hemoglobin ≥9 g/dL
- Serum bilirubin ≤1.5 time the upper limit of normal (ULN)
- Alanine aminotransferase and aspartate aminotransferase (AST) ≤2.5 x ULN
- Alkaline phosphatase ≤2.5 x ULN
- Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/m
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol
- Availability of genomic DNA (via whole blood)
Exclusion Criteria:
- Any prior treatment for primary invasive BC
- Metastatic, locally advanced or inflammatory (i.e., Stage III-IV) BC
- Bilateral invasive BC
- Multicentric BC, defined as the presence of two or more foci of cancer in different quadrants of the same breast
- Pre-existing peripheral neuropathy of any grade
- Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg)
- Clinically significant (i.e., active) cardiovascular disease
- Long QT syndrome
- Concomitant use of inhibitors of hepatic transport proteins such as organic anion-transporting proteins, P-glycoprotein, multidrug resistant proteins etc
- Major medical conditions that might affect study participation (e.g., uncontrolled seizure disorder, uncontrolled pulmonary, renal or hepatic dysfunction, or uncontrolled infection)
- Other primary malignant tumors within the previous 5 years, except for adequately controlled limited basal cell carcinoma of the skin or carcinoma in situ of the cervix
- Known human immunodeficiency virus(HIV) infection or other active or serious infection requiring IV antibiotics at randomization
- Pregnancy or breastfeeding women
- Women of childbearing potential(<2 years after the last menstruation) not using effective, non-hormonal means of contraception during the study and for a period of 6 months following the last administration of study drug
- Administration of any live virus vaccine within 8 weeks preceding study entry
- Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study
- Requirement for radiation therapy concurrent with study anticancer treatment
- Known hypersensitivity to any of the study drugs or excipients
- Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee
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: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Eribulin
1.23 mg/m2 eribulin ready to use solution (equivalent to 1.4 mg/m2 eribulin mesilate) IV on Days 1 and 8 of every 21-day cycle, for 4 cycles.
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1.23 mg/m2 eribulin ready to use solution (equivalent to 1.4 mg/m2 eribulin mesilate) IV on Days 1 and 8 of every 21-day cycle, for 4 cycles.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Correlation of pre-treatment relative abundance of hundreds of mRNA transcripts from primary breast tumors with pCRB after neoadjuvant treatment with eribulin.
Periodo de tiempo: At the time of definitive surgery.
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pCRB , defined as the complete absence of invasive carcinoma in the breast on histological examination at the time of definitive surgery, according to the NSABP guidelines
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At the time of definitive surgery.
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Rate of pCRB, defined as the complete absence of invasive carcinoma in the breast on histological examination at the time of definitive surgery, according to the NSABP guidelines.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Rate of pCRBL, defined as the complete absence of invasive carcinoma in the breast and axillary lymph nodes on histological examination at the time of definitive surgery.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Clinical and radiological ORR, defined by RECIST 1.1
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Correlation of mRNA expression in breast tumors with clinical and radiological ORR at different time points during the neoadjuvant treatment with eribulin.
Periodo de tiempo: Up to 21 weeks
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Up to 21 weeks
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Rate of pCRB according to breast cancer subtype: Luminal A, Luminal B, Basal-like, HER2-enriched and Claudin-low.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Rate of pCRB according to breast cancer subtype determined by immunohistochemistry (following the 2011 St. Gallen definitions): Luminal A, Luminal B, and TNBC.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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The correlation between alternations in tubulin isotype expression and mutational status in pre-treatment samples with efficacy parameters, such as pCRB, ORR and BOR.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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The correlation between exome or genome sequencing data from pre-treatment samples with pCRB after neoadjuvant treatment with eribulin.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Number of participants with AEs and serious AEs (assessed by CTCAE v.4)
Periodo de tiempo: Up to 21 weeks
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Up to 21 weeks
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Percentage of patients who had neutropenia Grade 3-4
Periodo de tiempo: Up to 21 weeks
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Up to 21 weeks
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Percentage of subjects with neuropathy
Periodo de tiempo: Up to 21 weeks
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Up to 21 weeks
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Incidence of dose reductions and/or dose delays due to treatment toxicity
Periodo de tiempo: Up to 71 days
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Up to 71 days
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Analysis of the expression of mRNA from breast tumors
Periodo de tiempo: At screening
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At screening
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Analysis of the expression of mRNA from breast tumors
Periodo de tiempo: At 21 days
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At 21 days
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Analysis of the expression of mRNA from breast tumors
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB.
Periodo de tiempo: At the time of definitive surgery
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At the time of definitive surgery
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Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At screening
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At screening
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Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At 21 days
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At 21 days
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Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At time of definitive surgery
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At time of definitive surgery
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Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At screening
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At screening
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Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At 21 days
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At 21 days
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Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Periodo de tiempo: At time of definitive surgery
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At time of definitive surgery
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Javier Cortés, MD, Hospital Universitario Vall d´Hebrón
- Investigador principal: Aleix Prat, MD, Vall d´Hebron Institut d´Oncologia
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
- Prat P, Llombart A, de la Peña L, Di Cosimo S, Oliveira M, Ortega V, Rubio I, Muñoz E, Harbeck N, Cortés J. NeoEribulin: A Phase II, non-randomized, open-label, single-arm, multicenter, exploratory pharmacogenomic study of single agent eribulin as neoadjuvant treatment for operable Stage I-II HER2 non-overexpressing breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.
Enlaces Útiles
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
1 de agosto de 2012
Finalización primaria (Actual)
1 de junio de 2015
Finalización del estudio (Actual)
1 de junio de 2015
Fechas de registro del estudio
Enviado por primera vez
9 de agosto de 2012
Primero enviado que cumplió con los criterios de control de calidad
16 de agosto de 2012
Publicado por primera vez (Estimar)
20 de agosto de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
6 de noviembre de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
31 de octubre de 2017
Última verificación
1 de octubre de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- SOLTI-1007
- 2012-000394-23 (Número EudraCT)
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. .