Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer (NeoEribulin)
31 oktober 2017 bijgewerkt door: 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.
Studie Overzicht
Studietype
Ingrijpend
Inschrijving (Werkelijk)
163
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Deggendorf, Duitsland, 94469
- Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum
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Köln, Duitsland, 51067
- Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.
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Munic, Duitsland, 81377
- Brustzentrum der Universität München
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Rostock, Duitsland, 18059
- Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik
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Villejuif, Frankrijk, 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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Barcelona, Spanje, 08025
- Hospital de La Santa Creu i Sant Pau
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Barcelona, Spanje
- Hospital Universitario Vall d´Hebron
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Barcelona, Spanje, 08035
- Hospital Universitario Vall d´Hebron
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Castelló de la Plana, Spanje, 12002
- Complejo Hospitalario de Castellón
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Cáceres, Spanje, 10003
- Complejo Hospitalario San Pedro de Alcántara
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Córdoba, Spanje, 14004
- Hospital Universitario Reina Sofia
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Denia, Spanje, 03700
- Hospital Marina Salud de Denia
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Jaén, Spanje, 23007
- Complejo Hospitalario de Jaén
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Lleida, Spanje, 25198
- Hospital Universitari Arnau de Vilanova de Lleida
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Madrid, Spanje, 28034
- Hospital Universitario Ramon y Cajal
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Madrid, Spanje, 28041
- Hospital Universitario 12 de Octubre
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Madrid, Spanje, 28040
- Hospital Universitario Clinico San Carlos
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Madrid, Spanje, 28222
- Hospital Universitario Puerta de Hierro de Majadahonda
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Murcia, Spanje, 30120
- Hospital Universitario Virgen de la Arrixaca
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Reus, Spanje, 43201
- Hospital Universitari Sant Joan de Reus
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Santiago de Compostela, Spanje, 15706
- Complejo Hospitalario Universitario de Santiago
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Sevilla, Spanje, 41013
- Hospital Universitario Virgen del Rocío
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Sevilla, Spanje, 41007
- Hospital Virgen de la Macarena
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Torrevieja, Spanje, 03186
- Hospital de Torrevieja
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Valencia, Spanje, 46010
- Hospital Clínico Universitario de Valencia
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Valencia, Spanje, 46015
- Hospital Arnau de Vilanova de Valencia
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Zaragoza, Spanje, 50009
- Hospital Universitario Lozano Blesa
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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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.
Tijdsspanne: 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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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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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.
Tijdsspanne: 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.
Tijdsspanne: 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
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: Up to 21 weeks
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Up to 21 weeks
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Percentage of subjects with neuropathy
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: At screening
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At screening
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Analysis of the expression of mRNA from breast tumors
Tijdsspanne: At 21 days
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At 21 days
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Analysis of the expression of mRNA from breast tumors
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: At time of definitive surgery
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At time of definitive surgery
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Javier Cortés, MD, Hospital Universitario Vall d´Hebron
- Hoofdonderzoeker: Aleix Prat, MD, Vall d´Hebron Institut d´Oncologia
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- 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.
Nuttige links
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 augustus 2012
Primaire voltooiing (Werkelijk)
1 juni 2015
Studie voltooiing (Werkelijk)
1 juni 2015
Studieregistratiedata
Eerst ingediend
9 augustus 2012
Eerst ingediend dat voldeed aan de QC-criteria
16 augustus 2012
Eerst geplaatst (Schatting)
20 augustus 2012
Updates van studierecords
Laatste update geplaatst (Werkelijk)
6 november 2017
Laatste update ingediend die voldeed aan QC-criteria
31 oktober 2017
Laatst geverifieerd
1 oktober 2017
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- SOLTI-1007
- 2012-000394-23 (EudraCT-nummer)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .