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

NCT01669252 | Completed Phase 2 DMC

• 2 other identifiers: SOLTI-10072012-000394-23
• Study Type: interventional
• Target: 163
• Locations: 4 countries
• Sites: 30

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Eribulin; Neoadjuvant; PAM50; Triple-negative; Luminal A; Luminal B

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• 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

• 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

• Clinical and radiological ORR, defined by RECIST 1.1

  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.

  Up to 21 weeks

• 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

Study Arms (1)

Eribulin

EXPERIMENTAL

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

Interventions

Eribulin DRUG

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.

Also known as: Halaven(R)

Eribulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• + expression by IHC
• + 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Eisai Inc.: collaborator

Study Sites (30)

Institut Gustave Roussy

Villejuif, 94800, France

Location

Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.

Cologne, 51067, Germany

Location

Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum

Deggendorf, 94469, Germany

Location

Brustzentrum der Universität München

Munich, 81377, Germany

Location

Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik

Rostock, 18059, Germany

Location

Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE

Coimbra, 3001-651, Portugal

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, Spain

Location

Complejo Hospitalario de Castellón

Castellon, 12002, Spain

Location

Complejo Hospitalario San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Marina Salud de Denia

Denia, 03700, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, 28222, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, 43201, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Virgen de la Macarena

Seville, 41007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital de Torrevieja

Torrevieja, 03186, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, 46015, Spain

Location

Hospital Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Related 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.

  BACKGROUND

Related Links

• SOLTI Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Javier Cortés, MD

  Hospital Universitario Vall d´Hebron

  PRINCIPAL INVESTIGATOR

• Aleix Prat, MD

  Vall d´Hebron Institut d´Oncologia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2012
• First Posted: August 20, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: November 6, 2017

Record last verified: 2017-10

Locations

FR (1); ES (22); PT (3); DE (4)