Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer (NeoEribulin)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by SOLTI Breast Cancer Research Group
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01669252
First received: August 9, 2012
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Eribulin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by SOLTI Breast Cancer Research Group:

Primary Outcome Measures:
  • Correlation of pre-treatment relative abundance of hundreds of mRNA transcripts from primary breast tumors with pCRB after neoadjuvant treatment with eribulin. [ Time Frame: At the time of definitive surgery. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Clinical and radiological ORR, defined by RECIST 1.1 [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Correlation of mRNA expression in breast tumors with clinical and radiological ORR at different time points during the neoadjuvant treatment with eribulin. [ Time Frame: Up to 21 weeks ] [ Designated as safety issue: No ]
  • Rate of pCRB according to breast cancer subtype: Luminal A, Luminal B, Basal-like, HER2-enriched and Claudin-low. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Rate of pCRB according to breast cancer subtype determined by immunohistochemistry (following the 2011 St. Gallen definitions): Luminal A, Luminal B, and TNBC. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • The correlation between alternations in tubulin isotype expression and mutational status in pre-treatment samples with efficacy parameters, such as pCRB, ORR and BOR. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • The correlation between exome or genome sequencing data from pre-treatment samples with pCRB after neoadjuvant treatment with eribulin. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Number of participants with AEs and serious AEs (assessed by CTCAE v.4) [ Time Frame: Up to 21 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients who had neutropenia Grade 3-4 [ Time Frame: Up to 21 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with neuropathy [ Time Frame: Up to 21 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of dose reductions and/or dose delays due to treatment toxicity [ Time Frame: Up to 71 days ] [ Designated as safety issue: Yes ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At screening ] [ Designated as safety issue: No ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At 21 days ] [ Designated as safety issue: No ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB. [ Time Frame: At the time of definitive surgery ] [ Designated as safety issue: No ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At screening ] [ Designated as safety issue: No ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At 21 days ] [ Designated as safety issue: No ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At time of definitive surgery ] [ Designated as safety issue: No ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At screening ] [ Designated as safety issue: No ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At 21 days ] [ Designated as safety issue: No ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At time of definitive surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: August 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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.
Other Name: Halaven(R)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01669252

Contacts
Contact: Javier Cortés Castán +34 93 489 43 50 jacortes@vhebron.net

Locations
France
Institut Gustave Roussy Active, not recruiting
Villejuif, France, 94800
Germany
Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum Recruiting
Deggendorf, Germany, 94469
Contact: Doris Augustin    +49 991 380 31 71    doris.augustin@klinikum-deggendorf.de   
Principal Investigator: Doris Augustin         
Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz. Active, not recruiting
Köln, Germany, 51067
Brustzentrum der Universität München Recruiting
Munic, Germany, 81377
Contact: Nadia Harbeck    +49 89 7095 7581    nadia.harbeck@med.uni-muenchen.de   
Principal Investigator: Nadia Harbeck         
Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik Recruiting
Rostock, Germany, 18059
Contact: Toralf Reimer    +49 381 4401 4500    toralf.reimer@med.uni-rostock.de   
Principal Investigator: Toralf Reimer         
Portugal
Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE Not yet recruiting
Coimbra, Portugal, 3001-651
Contact: Sofia Broco    +351 239 400 200      
Principal Investigator: Sofia Broco         
Hospital da Luz Not yet recruiting
Lisboa, Portugal, 1500-650
Contact: Monica Nave    +35 92 660 96 49    mnave@hospitaldaluz.pt   
Principal Investigator: Monica Nave         
Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE Not yet recruiting
Porto, Portugal, 4200-072
Contact: Helena Rodrigues    +351225084000 ext 7649    hrodrigues@ipoporto.min-saude.pt   
Principal Investigator: Helena Rodrigues         
Spain
Hospital Universitario Vall d´Hebron Recruiting
Barcelona, Spain
Contact: Javier Cortés Castán    93 489 43 50    jacortes@vhebron.net   
Principal Investigator: Javier Cortes         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Belén Ojeda    +34 93 556 56 51    mojeda@santpau.es   
Principal Investigator: Belén Ojeda         
Hospital Universitario Vall d´Hebron Recruiting
Barcelona, Spain, 08035
Contact: Vanesa Ortega    +34 605 925 779    vortega@vhebron.net   
Principal Investigator: Vanesa Ortega         
Complejo Hospitalario de Castellón Recruiting
Castellón, Spain, 12002
Contact: Eduardo Martínez    +34 964354458    eduardo.martinez@hospital2000.net   
Principal Investigator: Eduardo Martínez         
Complejo Hospitalario San Pedro de Alcántara Active, not recruiting
Cáceres, Spain, 10003
Hospital Universitario Reina Sofia Recruiting
Córdoba, Spain, 14004
Contact: Juan Rafael De la Haba    +34 957 011 893    juahaba@gmail.com   
Principal Investigator: Juan Rafael De la Haba         
Hospital Marina Salud de Denia Active, not recruiting
Denia, Spain, 03700
Complejo Hospitalario de Jaén Recruiting
Jaén, Spain, 23007
Contact: Pedro Sánchez Rovira    +34 953 22 03 06    oncopsr@yahoo.es   
Principal Investigator: Pedro Sánchez Rovira         
Hospital Universitari Arnau de Vilanova de Lleida Recruiting
Lleida, Spain, 25198
Contact: Serafín Morales    +34 973 24 81 00 ext 2806    serafinmorales01@gmail.com   
Principal Investigator: Serafín Morales         
Hospital Universitario Puerta de Hierro de Majadahonda Active, not recruiting
Madrid, Spain, 28222
Hospital Universitario Clínico San Carlos Active, not recruiting
Madrid, Spain, 28040
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain, 28034
Contact: Noelia Marínez    +3491 336 82 63    mjnoelia@hotmail.com   
Principal Investigator: Noelia Marínez         
Hospital Universitario 12 de Octubre Active, not recruiting
Madrid, Spain, 28041
Hospital Universitario Virgen de la Arrixaca Active, not recruiting
Murcia, Spain, 30120
Hospital Universitari Sant Joan de Reus Recruiting
Reus, Spain, 43201
Contact: Kepa Amillano    +34 977 310300 ext 5517    kamillano@grupsagessa.cat   
Principal Investigator: Kepa Amillano         
Complejo Hospitalario Universitario de Santiago Recruiting
Santiago de Compostela, Spain, 15706
Contact: Rafael López    +34981950512    rafael.lopez.lopez@sergas.es   
Principal Investigator: Rafael López         
Hospital Virgen de la Macarena Active, not recruiting
Sevilla, Spain, 41007
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Rosario González    +34 955 013 068    rgonzalezmancha@telefonica.net   
Principal Investigator: Rosario González         
Hospital de Torrevieja Recruiting
Torrevieja, Spain, 03186
Contact: Juan Carlos Toral    +34 965 721 341 ext 1554    jctoral@torrevieja-salud.com   
Principal Investigator: Juan Carlos Toral         
Hospital Arnau de Vilanova de Valencia Active, not recruiting
Valencia, Spain, 46015
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Ana Lluch    +34 963862600 ext 51306    begobermejo@gmail.com   
Principal Investigator: Ana Lluch         
Hospital Universitario Lozano Blesa Recruiting
Zaragoza, Spain, 50009
Contact: Raquel Andres    +34976765746    lmjaso@yahoo.es   
Principal Investigator: Raquel Andres         
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Eisai Inc.
Investigators
Principal Investigator: Javier Cortés, MD Hospital Universitario Vall d´Hebron
Principal Investigator: Aleix Prat, MD Vall d´Hebron Institut d´Oncologia
  More Information

Additional Information:
No publications provided

Responsible Party: SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01669252     History of Changes
Other Study ID Numbers: SOLTI-1007, 2012-000394-23
Study First Received: August 9, 2012
Last Updated: February 11, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by SOLTI Breast Cancer Research Group:
Breast cancer
Eribulin
Neoadjuvant
PAM50
Triple-negative
Luminal A
Luminal B

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 26, 2014