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

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ClinicalTrials.gov Identifier: NCT01669252
Recruitment Status : Completed
First Posted : August 20, 2012
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group

Tracking Information
First Submitted Date  ICMJE August 9, 2012
First Posted Date  ICMJE August 20, 2012
Last Update Posted Date November 6, 2017
Study Start Date  ICMJE August 2012
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2012)
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. ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2012)
  • 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 ]
  • 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 ]
  • Clinical and radiological ORR, defined by RECIST 1.1 [ Time Frame: 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. [ Time Frame: Up to 21 weeks ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Number of participants with AEs and serious AEs (assessed by CTCAE v.4) [ Time Frame: Up to 21 weeks ]
  • Percentage of patients who had neutropenia Grade 3-4 [ Time Frame: Up to 21 weeks ]
  • Percentage of subjects with neuropathy [ Time Frame: Up to 21 weeks ]
  • Incidence of dose reductions and/or dose delays due to treatment toxicity [ Time Frame: Up to 71 days ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At screening ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At 21 days ]
  • Analysis of the expression of mRNA from breast tumors [ Time Frame: At the time of definitive surgery ]
  • 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 ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At screening ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At 21 days ]
  • Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At time of definitive surgery ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At screening ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At 21 days ]
  • Specificity of the gene expression analysis of samples to predict clinical response to eribulin. [ Time Frame: At time of definitive surgery ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer
Official Title  ICMJE 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.
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE 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)
Study Arms  ICMJE 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.
Intervention: Drug: Eribulin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 5, 2015)
163
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2012)
200
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Portugal,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01669252
Other Study ID Numbers  ICMJE SOLTI-1007
2012-000394-23 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SOLTI Breast Cancer Research Group
Study Sponsor  ICMJE SOLTI Breast Cancer Research Group
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE
Principal Investigator: Javier Cortés, MD Hospital Universitario Vall d´Hebron
Principal Investigator: Aleix Prat, MD Vall d´Hebron Institut d´Oncologia
PRS Account SOLTI Breast Cancer Research Group
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP