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

Breast Cancer Clinical Trial

— NeoEribulin  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01669252
• Other study ID #: SOLTI-1007
• Secondary ID: 2012-000394-23
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2012
• Last updated: October 31, 2017
• Start date: August 2012
• Est. completion date: June 2015

Study information

• Verified date: October 2017
• Source: SOLTI Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif
Germany	Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum	Deggendorf
Germany	Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.	Köln
Germany	Brustzentrum der Universität München	Munic
Germany	Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik	Rostock
Portugal	Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE	Coimbra
Portugal	Hospital da Luz	Lisboa
Portugal	Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE	Porto
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	Complejo Hospitalario San Pedro de Alcántara	Cáceres
Spain	Complejo Hospitalario de Castellón	Castelló de la Plana
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Marina Salud de Denia	Denia
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital Universitari Arnau de Vilanova de Lleida	Lleida
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitari Sant Joan de Reus	Reus
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Virgen de la Macarena	Sevilla
Spain	Hospital de Torrevieja	Torrevieja
Spain	Hospital Arnau de Vilanova de Valencia	Valencia
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
SOLTI Breast Cancer Research Group	Eisai Inc.

Countries where clinical trial is conducted

France,  Germany,  Portugal,  Spain, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of pre-treatment relative abundance of hundreds of mRNA transcripts from primary breast tumors with pCRB after neoadjuvant treatment with eribulin.	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.
Secondary	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.		At the time of definitive surgery
Secondary	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.		At the time of definitive surgery
Secondary	Clinical and radiological ORR, defined by RECIST 1.1		At the time of definitive surgery
Secondary	Correlation of mRNA expression in breast tumors with clinical and radiological ORR at different time points during the neoadjuvant treatment with eribulin.		Up to 21 weeks
Secondary	Rate of pCRB according to breast cancer subtype: Luminal A, Luminal B, Basal-like, HER2-enriched and Claudin-low.		At the time of definitive surgery
Secondary	Rate of pCRB according to breast cancer subtype determined by immunohistochemistry (following the 2011 St. Gallen definitions): Luminal A, Luminal B, and TNBC.		At the time of definitive surgery
Secondary	Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy.		At the time of definitive surgery
Secondary	The correlation between alternations in tubulin isotype expression and mutational status in pre-treatment samples with efficacy parameters, such as pCRB, ORR and BOR.		At the time of definitive surgery
Secondary	The correlation between exome or genome sequencing data from pre-treatment samples with pCRB after neoadjuvant treatment with eribulin.		At the time of definitive surgery
Secondary	Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment.		At the time of definitive surgery
Secondary	Number of participants with AEs and serious AEs (assessed by CTCAE v.4)		Up to 21 weeks
Secondary	Percentage of patients who had neutropenia Grade 3-4		Up to 21 weeks
Secondary	Percentage of subjects with neuropathy		Up to 21 weeks
Secondary	Incidence of dose reductions and/or dose delays due to treatment toxicity		Up to 71 days
Secondary	Analysis of the expression of mRNA from breast tumors		At screening
Secondary	Analysis of the expression of mRNA from breast tumors		At 21 days
Secondary	Analysis of the expression of mRNA from breast tumors		At the time of definitive surgery
Secondary	Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB.		At the time of definitive surgery
Secondary	Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.		At screening
Secondary	Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.		At 21 days
Secondary	Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.		At time of definitive surgery
Secondary	Specificity of the gene expression analysis of samples to predict clinical response to eribulin.		At screening
Secondary	Specificity of the gene expression analysis of samples to predict clinical response to eribulin.		At 21 days
Secondary	Specificity of the gene expression analysis of samples to predict clinical response to eribulin.		At time of definitive surgery

External Links

•   SOLTI Breast Cancer Research Group