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

August 9, 2012
February 11, 2013
August 2012
August 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01669252 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer
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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
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)
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
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.
 
Recruiting
200
August 2017
August 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Javier Cortés Castán +34 93 489 43 50 jacortes@vhebron.net
France,   Germany,   Portugal,   Spain
 
NCT01669252
SOLTI-1007, 2012-000394-23
Yes
SOLTI Breast Cancer Research Group
SOLTI Breast Cancer Research Group
Eisai Inc.
Principal Investigator: Javier Cortés, MD Hospital Universitario Vall d´Hebron
Principal Investigator: Aleix Prat, MD Vall d´Hebron Institut d´Oncologia
SOLTI Breast Cancer Research Group
February 2013

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