Inclusion Criteria:
1. Signed informed consent form
2. Age 18 years or older
3. Patients with histologically or cytological confirmed carcinoma of the breast.
Patients with locally recurrent or metastatic disease
4. Patients with HR-positive, HER negative tumors or triple negative tumors
5. Previous chemotherapies (neo, adjuvant or in the metastatic setting) must have
included a taxane and an anthracycline unless anthracycline therapy is not indicated.
6. Maximum of three (3) prior chemotherapies in the metastatic setting in addition to any
number of prior lines of endocrine therapy
7. Measurable disease
8. Performance status of ECOG ≤ 1
9. With an Ixabepilone DRP - score of >67%
10. Adequate conditions as evidenced by the following clinical laboratory values:
1. Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
2. Hemoglobin > 6.0 mmol/L
3. Platelets ≥ 100 x 109 /L
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
5. Serum bilirubin ≤ 1.0 ULN
6. Alkaline phosphatase ≤ 2.5 x ULN Creatinine ≤ 1.5 ULN
7. Blood urea within normal limits
11. Because of possible interference of cytochrome P450 3A4 activity by ixabepilone,
patients were excluded from receiving the following medications at enrollment and
while enrolled onto the study: amiodarone, clarithromycin, erythromycin, fluconazole,
itraconazole, ketoconazole, indinavir, nelfinavir, ritonavir, and saquinavir
12. Women of childbearing age and potential must be willing to use effective contraception
during the study and at least until 90 days after last dose of study drug. Male
patients or male patients who have female partners of childbearing age and potential
must be willing to use effective contraception during the study and at least until 90
days after last dose of study drug. Highly effective methods of birth control are
defined as those which result in a low failure rate (i.e. less than 1% per year) when
used consistently and correctly such as intrauterine devices or hormonal contraception
(oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting
injections)
Exclusion Criteria:
1. Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug
except non-disease related conditions (e.g. insulin for diabetes) during study period
2. Patients with intracranial disease
3. Other malignancy with exception of curative treated non-melanoma skin cancer or
cervical carcinoma in situ within 5 years prior to entering the study
4. Any active infection requiring parenteral or oral antibiotic treatment.
5. Patients with grade 2, in case of diabetes grade 1 or greater neuropathy
6. Clinically significant (i.e. active) cardiovascular disease:
7. Stroke within ≤ 6 months prior to day 1
8. Transient ischemic attach (TIA) within ≤ 6 months prior to day 1
9. Myocardial infarction within ≤ 6 months prior to day 1
10. Unstable angina
11. New York Hart Association (NYHA) Class II or greater congestive heart failure (CHF)
12. Serious cardiac arrhythmia requiring medication
13. Other medications or conditions, including surgery, that in the Investigator's opinion
would contraindicate study participation for safety reasons or interfere with the
interpretation of study results.
14. Requiring immediate palliative treatment of any kind including surgery and/or
radiotherapy
15. Female patients who are pregnant or breast-feeding (pregnancy test with a positive
result before study entry)
16. Known prior severe hypersensitivity reactions to agents containing polyoxyethylated
castor oil (Cremophor EL)
17. Known hypersensitivity to fluoropyrimidines;
18. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency;
19. Patients must not continue treatment with the following strong inhibitors of CYP3A4:
ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and
voriconazole. These therapies should be discontinued 72 hours prior to initiation of study
drug therapy.