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

• Conditions: Patients at Stage I-II HER2-negative breast cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-000394-23-DE
• Lead Sponsor: SOLTI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-30
• Last Update Posted: 25 January 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Written IC must be given according to ICH/GCP guidelines and national/local regulations before patient registration, specifically highlighting the generation of molecular characterization of tumor and genomic samples.
2. Age =18 years.
3. Histologically confirmed invasive breast carcinoma with all of the following characteristics:
a. Primary tumor =2 cm in largest diameter (cT1-3) assessed by physical examination and mammography and/or breast US and/or breast MRI (where available). If the tumor is not palpable or measures less than 2 cm in physical examination, the patient is eligible if the imaging technique (mammography and/or breast US and/or breast MRI) shows a tumor of at least 2 cm.
b. cN0-1: patients with clinically evident axillary lymph nodes can be included, but not if metastasis in ipsilateral level I/II axillary lymph nodes are fixed to one another (matted) or to other structures (N2a). Patients with clinically involved internal mammary or supraclavicular nodes (i.e., cN2b-3) are also excluded.
c. No evidence of distant metastasis (M0).
4. BC must be eligible for definitive primary surgery.
5. Available pre-treatment core (Tru-cut) biopsy or possibility of performing one.
6. HER2- BC (as per local assessment), defined by any of the following:
a. 0-1+ expression by IHC.
b. 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).
c. Is situ hybridization (FISH/CISH) without HER2 gene amplification, independently of IHC.
7. Known hormone receptor (ER/PgR) status (as per local assessment) or possibility of performing the tests.
8. Known percentage of hormone receptor (ER/PgR) and Ki67-positive tumor cells (as per local assessment), or possibility of performing the tests.
9. Multifocal tumors (defined as the presence of two or more foci of cancer within the same breast quadrant) are allowed. However, if a multifocal tumor is present:
a. The largest lesion must be =2 cm. It will be considered as the target lesion for all subsequent tumor evaluations.
b. HER2- status must be documented in all the tumor foci.
c. ER/PgR status of the target lesion will be considered to classify the BC subtype, as determined by IHC criteria.
10. ECOG performance status of 0 or 1 (see Appendix B for definitions).
11. Adequate laboratory values as follows:
a. Absolute neutrophil count (ANC) =1.5 x 109/L.
b. Platelets count =100 x 109/L.
c. Hemoglobin =9 g/dL.
d. Serum bilirubin =1.5 time the upper limit of normal (ULN). In the case of known Gilbert’s syndrome, a higher serum total bilirubin (<2 x ULN) is allowed.
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 x ULN.
f. Alkaline phosphatase (AP) =2.5 x ULN.
g. Serum creatinine =1.5 mg/dL or calculated creatinine clearance =60 mL/m.
12. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
13. Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol; those conditions should be discussed with the patient before registration in the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Any prior treatment for primary invasive BC.
2. Metastatic, locally advanced, or inflammatory BC (i.e., Stage III or IV BC).
3. Bilateral invasive BC.
4. Multicentric BC, defined as the presence of two or more foci of cancer in different quadrants of the same breast.
5. Pre-existing peripheral neuropathy of any grade.
6. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100mmHg).
7. Clinically significant (i.e., active) cardiovascular disease, including cerebrovascular accident (=6 months before enrolment), myocardial infarction (=6 months before enrolment), unstable angina, New York Heart Association = grade 2 congestive heart failure, serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment, or not controlled by medication.
8. Long QT syndrome.
9. Concomitant use of inhibitors of hepatic transport proteins, such as organic anion-transporting proteins (OATPs), P-glycoprotein (Pgp), multidrug resistant proteins (MRPs), etc. Inhibitors of such transporters include but are not limited to: cyclosporine, ritonavir, saquinavir, lopinavir, and certain other protease inhibitors, efavirenz, emtricitabine, verapamil, clarithromycin, quinine, quinidine and disopyramide.
10. Major medical conditions that might affect study participation (e.g., active peptic ulcer disease, uncontrolled diabetes mellitus, uncontrolled seizure disorder, uncontrolled pulmonary, renal or hepatic dysfunction, or uncontrolled infection).
11. 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.
12. Known human immunodeficiency virus (HIV) infection or other active or serious infection requiring IV antibiotics at enrollment.
13. Pregnancy or breastfeeding women.
14. Women of childbearing potential (<2 years after the last menstruation) not using effective, non-hormonal means of contraception (e.g., intra-uterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterilized) during the study and for a period of 6 months following the last administration of study drug.
15. Administration of any live virus vaccine within 8 weeks preceding study entry.
16. Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical study.
17. Requirement for radiation therapy concurrent with study anticancer treatment. Patients who require breast or chest wall radiation therapy after surgery are eligible.
18. Known hypersensitivity to the study drug or excipients.
19. Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator or designee.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified