Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer (NeoEribulin)
31. oktober 2017 oppdatert av: 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.
Studieoversikt
Studietype
Intervensjonell
Registrering (Faktiske)
163
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
-
Villejuif, Frankrike, 94800
- Institut Gustave Roussy
-
-
-
-
-
Coimbra, Portugal, 3001-651
- Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE
-
Lisboa, Portugal, 1500-650
- Hospital da Luz
-
Porto, Portugal, 4200-072
- Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
-
-
-
-
-
Barcelona, Spania, 08025
- Hospital de La Santa Creu i Sant Pau
-
Barcelona, Spania
- Hospital Universitario Vall d´Hebron
-
Barcelona, Spania, 08035
- Hospital Universitario Vall d´Hebron
-
Castelló de la Plana, Spania, 12002
- Complejo Hospitalario de Castellón
-
Cáceres, Spania, 10003
- Complejo Hospitalario San Pedro de Alcántara
-
Córdoba, Spania, 14004
- Hospital Universitario Reina Sofia
-
Denia, Spania, 03700
- Hospital Marina Salud de Denia
-
Jaén, Spania, 23007
- Complejo Hospitalario de Jaén
-
Lleida, Spania, 25198
- Hospital Universitari Arnau de Vilanova de Lleida
-
Madrid, Spania, 28034
- Hospital Universitario Ramon y Cajal
-
Madrid, Spania, 28041
- Hospital Universitario 12 de Octubre
-
Madrid, Spania, 28040
- Hospital Universitario Clinico San Carlos
-
Madrid, Spania, 28222
- Hospital Universitario Puerta de Hierro de Majadahonda
-
Murcia, Spania, 30120
- Hospital Universitario Virgen de la Arrixaca
-
Reus, Spania, 43201
- Hospital Universitari Sant Joan de Reus
-
Santiago de Compostela, Spania, 15706
- Complejo Hospitalario Universitario de Santiago
-
Sevilla, Spania, 41013
- Hospital Universitario Virgen del Rocío
-
Sevilla, Spania, 41007
- Hospital Virgen de la Macarena
-
Torrevieja, Spania, 03186
- Hospital de Torrevieja
-
Valencia, Spania, 46010
- Hospital Clínico Universitario de Valencia
-
Valencia, Spania, 46015
- Hospital Arnau de Vilanova de Valencia
-
Zaragoza, Spania, 50009
- Hospital Universitario Lozano Blesa
-
-
-
-
-
Deggendorf, Tyskland, 94469
- Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum
-
Köln, Tyskland, 51067
- Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.
-
Munic, Tyskland, 81377
- Brustzentrum der Universität München
-
Rostock, Tyskland, 18059
- Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
|
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.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Correlation of pre-treatment relative abundance of hundreds of mRNA transcripts from primary breast tumors with pCRB after neoadjuvant treatment with eribulin.
Tidsramme: At the time of definitive surgery.
|
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
|
At the time of definitive surgery.
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
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.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
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.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Clinical and radiological ORR, defined by RECIST 1.1
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Correlation of mRNA expression in breast tumors with clinical and radiological ORR at different time points during the neoadjuvant treatment with eribulin.
Tidsramme: Up to 21 weeks
|
Up to 21 weeks
|
|
Rate of pCRB according to breast cancer subtype: Luminal A, Luminal B, Basal-like, HER2-enriched and Claudin-low.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Rate of pCRB according to breast cancer subtype determined by immunohistochemistry (following the 2011 St. Gallen definitions): Luminal A, Luminal B, and TNBC.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
The correlation between alternations in tubulin isotype expression and mutational status in pre-treatment samples with efficacy parameters, such as pCRB, ORR and BOR.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
The correlation between exome or genome sequencing data from pre-treatment samples with pCRB after neoadjuvant treatment with eribulin.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Number of participants with AEs and serious AEs (assessed by CTCAE v.4)
Tidsramme: Up to 21 weeks
|
Up to 21 weeks
|
|
Percentage of patients who had neutropenia Grade 3-4
Tidsramme: Up to 21 weeks
|
Up to 21 weeks
|
|
Percentage of subjects with neuropathy
Tidsramme: Up to 21 weeks
|
Up to 21 weeks
|
|
Incidence of dose reductions and/or dose delays due to treatment toxicity
Tidsramme: Up to 71 days
|
Up to 71 days
|
|
Analysis of the expression of mRNA from breast tumors
Tidsramme: At screening
|
At screening
|
|
Analysis of the expression of mRNA from breast tumors
Tidsramme: At 21 days
|
At 21 days
|
|
Analysis of the expression of mRNA from breast tumors
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB.
Tidsramme: At the time of definitive surgery
|
At the time of definitive surgery
|
|
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At screening
|
At screening
|
|
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At 21 days
|
At 21 days
|
|
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At time of definitive surgery
|
At time of definitive surgery
|
|
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At screening
|
At screening
|
|
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At 21 days
|
At 21 days
|
|
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Tidsramme: At time of definitive surgery
|
At time of definitive surgery
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Javier Cortés, MD, Hospital Universitario Vall d´Hebron
- Hovedetterforsker: Aleix Prat, MD, Vall d´Hebron Institut d´Oncologia
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. august 2012
Primær fullføring (Faktiske)
1. juni 2015
Studiet fullført (Faktiske)
1. juni 2015
Datoer for studieregistrering
Først innsendt
9. august 2012
Først innsendt som oppfylte QC-kriteriene
16. august 2012
Først lagt ut (Anslag)
20. august 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
6. november 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
31. oktober 2017
Sist bekreftet
1. oktober 2017
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- SOLTI-1007
- 2012-000394-23 (EudraCT-nummer)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .