- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01669252
Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer (NeoEribulin)
31 octobre 2017 mis à jour par: 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.
Aperçu de l'étude
Type d'étude
Interventionnel
Inscription (Réel)
163
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Deggendorf, Allemagne, 94469
- Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum
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Köln, Allemagne, 51067
- Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.
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Munic, Allemagne, 81377
- Brustzentrum der Universität München
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Rostock, Allemagne, 18059
- Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik
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Barcelona, Espagne, 08025
- Hospital De La Santa Creu I Sant Pau
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Barcelona, Espagne
- Hospital Universitario Vall D´Hebrón
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Barcelona, Espagne, 08035
- Hospital Universitario Vall D´Hebrón
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Castelló de la Plana, Espagne, 12002
- Complejo Hospitalario de Castellón
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Cáceres, Espagne, 10003
- Complejo Hospitalario San Pedro de Alcantara
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Córdoba, Espagne, 14004
- Hospital Universitario Reina Sofia
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Denia, Espagne, 03700
- Hospital Marina Salud de Dénia
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Jaén, Espagne, 23007
- Complejo Hospitalario de Jaén
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Lleida, Espagne, 25198
- Hospital Universitari Arnau de Vilanova de Lleida
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Madrid, Espagne, 28034
- Hospital Universitario Ramón Y Cajal
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Madrid, Espagne, 28041
- Hospital Universitario 12 de Octubre
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Madrid, Espagne, 28040
- Hospital Universitario Clinico San Carlos
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Madrid, Espagne, 28222
- Hospital Universitario Puerta De Hierro De Majadahonda
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Murcia, Espagne, 30120
- Hospital Universitario Virgen de la Arrixaca
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Reus, Espagne, 43201
- Hospital Universitari Sant Joan de Reus
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Santiago de Compostela, Espagne, 15706
- Complejo Hospitalario Universitario de Santiago
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Sevilla, Espagne, 41013
- Hospital Universitario Virgen del Rocio
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Sevilla, Espagne, 41007
- Hospital Virgen de la Macarena
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Torrevieja, Espagne, 03186
- Hospital de Torrevieja
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Valencia, Espagne, 46010
- Hospital Clínico Universitario de Valencia
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Valencia, Espagne, 46015
- Hospital Arnau de Vilanova de Valencia
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Zaragoza, Espagne, 50009
- Hospital Universitario Lozano Blesa
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Villejuif, France, 94800
- Institut Gustave Roussy
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Coimbra, Le Portugal, 3001-651
- Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE
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Lisboa, Le Portugal, 1500-650
- Hospital da Luz
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Porto, Le Portugal, 4200-072
- Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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 d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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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.
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Délai |
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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.
Délai: 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.
Délai: 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
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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)
Délai: 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
Délai: Up to 21 weeks
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Up to 21 weeks
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Percentage of subjects with neuropathy
Délai: 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
Délai: 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
Délai: At screening
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At screening
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Analysis of the expression of mRNA from breast tumors
Délai: At 21 days
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At 21 days
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Analysis of the expression of mRNA from breast tumors
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: 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.
Délai: At time of definitive surgery
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At time of definitive surgery
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Javier Cortés, MD, Hospital Universitario Vall D´Hebrón
- Chercheur principal: Aleix Prat, MD, Vall d´Hebron Institut d´Oncologia
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 août 2012
Achèvement primaire (Réel)
1 juin 2015
Achèvement de l'étude (Réel)
1 juin 2015
Dates d'inscription aux études
Première soumission
9 août 2012
Première soumission répondant aux critères de contrôle qualité
16 août 2012
Première publication (Estimation)
20 août 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
6 novembre 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
31 octobre 2017
Dernière vérification
1 octobre 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- SOLTI-1007
- 2012-000394-23 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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