Breast CancerPhase 2NeoEribulinNCT01669252
Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer
A Phase 2 study testing Eribulin in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 30 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Eribulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 163 participants
- Where
- 30 sitesin 4 countries
- Study dates
- Aug 2012to Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 27Show fewer
- 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)
Who cannot join
- 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)
Show all 19Show fewer
- 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
Trial locations and contacts
30 sites in 4 countries.
30 sites in 4 countries
Spain22 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitario Vall d´Hebron
Barcelona, 08035
Hospital Universitario Vall d´Hebron
Barcelona
Complejo Hospitalario San Pedro de Alcántara
Cáceres, 10003
Complejo Hospitalario de Castellón
Castellon, 12002
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Marina Salud de Denia
Denia, 03700
Complejo Hospitalario de Jaén
Jaén, 23007
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, 25198
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Clínico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro de Majadahonda
Madrid, 28222
Hospital Universitario Virgen de la Arrixaca
Murcia, 30120
Hospital Universitari Sant Joan de Reus
Reus, 43201
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706
Hospital Virgen de la Macarena
Seville, 41007
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital de Torrevieja
Torrevieja, 03186
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Arnau de Vilanova de Valencia
Valencia, 46015
Hospital Universitario Lozano Blesa
Zaragoza, 50009
Germany4 sites
Brustzentrum im Krankenhaus Köln-Holweide Priv. Doz.
Cologne, 51067
Klinikum des Landkreises Deggendorf Frauenklinik Mammazentrum
Deggendorf, 94469
Brustzentrum der Universität München
Munich, 81377
Klinikum Südstadt Rostock, Universitätsfrauenklinik und Poliklinik
Rostock, 18059
Portugal3 sites
Instituto Portugues de Oncologia de Coimbra Francisco Gentil, EPE
Coimbra, 3001-651
Hospital da Luz
Lisbon, 1500-650
Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
Porto, 4200-072
About this study
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.
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
- Being tested
- Eribulin
- Keywords
- Breast cancer, Eribulin, Neoadjuvant, PAM50, Triple-negative, Luminal A, Luminal B
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EribulinDrug
Also called Halaven(R)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Eribulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: At the time of definitive surgery
Clinical and radiological ORR, defined by RECIST 1.1
Measured: 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.
Measured: Up to 21 weeks
Rate of pCRB according to breast cancer subtype: Luminal A, Luminal B, Basal-like, HER2-enriched and Claudin-low.
Measured: 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.
Measured: At the time of definitive surgery
Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy.
Measured: 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.
Measured: 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.
Measured: At the time of definitive surgery
Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment.
Measured: At the time of definitive surgery
Number of participants with AEs and serious AEs (assessed by CTCAE v.4)
Measured: Up to 21 weeks
Percentage of patients who had neutropenia Grade 3-4
Measured: Up to 21 weeks
Percentage of subjects with neuropathy
Measured: Up to 21 weeks
Incidence of dose reductions and/or dose delays due to treatment toxicity
Measured: Up to 71 days
Analysis of the expression of mRNA from breast tumors
Measured: At screening
Analysis of the expression of mRNA from breast tumors
Measured: At 21 days
Analysis of the expression of mRNA from breast tumors
Measured: At the time of definitive surgery
Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB.
Measured: At the time of definitive surgery
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At screening
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At 21 days
Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At time of definitive surgery
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At screening
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At 21 days
Specificity of the gene expression analysis of samples to predict clinical response to eribulin.
Measured: At time of definitive surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- SOLTI Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Javier Cortés, MD, Principal investigator, Hospital Universitario Vall d´HebronAleix Prat, MD, Principal investigator, Vall d´Hebron Institut d´Oncologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01669252
- Sponsor's protocol ID
- SOLTI-1007
- Other IDs
- 2012-000394-23
- Acronym
- NeoEribulin
- Status last verified
- Oct 2017
- First submitted
- 9 Aug 2012
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01669252
- Acronym / sponsor ID
- NeoEribulin / SOLTI-1007
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Eribulin, Neoadjuvant, PAM50, Triple-negative, Luminal A, Luminal B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- SOLTI Breast Cancer Research GroupUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Aug 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 20 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eribulin | Experimental | Drug: Eribulin1.23 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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:
- Breast cancer (BC) eligible for primary surgery
- Available pre-treatment core (Tru-cut) biopsy or possibility of performing one
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EribulinAlso: Halaven(R)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 |
Primary outcome
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
24 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- BackgroundPrat 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.
- SOLTI Breast Cancer Research GroupLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javier Cortés, MD principal investigator
Hospital Universitario Vall d´Hebron
Aleix Prat, MD principal investigator
Vall d´Hebron Institut d´Oncologia
30 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eribulin in people with Breast Cancer, run by SOLTI Breast Cancer Research Group at 30 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, Germany, Portugal, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01669252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.