Breast Cancer
Conditions
Keywords
Breast cancer, Eribulin, Neoadjuvant, PAM50, Triple-negative, Luminal A, Luminal B
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.
Interventions
DRUGEribulin
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.
Sponsors
Eisai Inc.
SOLTI Breast Cancer Research Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of pre-treatment relative abundance of hundreds of mRNA transcripts from primary breast tumors with pCRB after neoadjuvant treatment with eribulin. | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Proportion of patients able to have breast conservation surgery after being treated with eribulin as neoadjuvant therapy. | 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. | 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. | At the time of definitive surgery |
| 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 |
| Number of participants with AEs and serious AEs (assessed by CTCAE v.4) | Up to 21 weeks |
| Percentage of patients who had neutropenia Grade 3-4 | Up to 21 weeks |
| Percentage of subjects with neuropathy | Up to 21 weeks |
| Incidence of dose reductions and/or dose delays due to treatment toxicity | Up to 71 days |
| Analysis of the expression of mRNA from breast tumors | At screening |
| Correlation of mRNA expression in breast tumors after 21 days of neoadjuvant treatment and at surgery with pCRB. | At the time of definitive surgery |
| Sensitivity of the gene expression analysis of samples to predict clinical response to eribulin. | At screening |
| Specificity of the gene expression analysis of samples to predict clinical response to eribulin. | At screening |
| Changes in gene expression and gene mutational status between the pre-treatment samples and samples after treatment. | At the time of definitive surgery |
Countries
France, Germany, Portugal, Spain
Outcome results
None listed