Intervention: Paclitaxel
Trial phase: Phase 2
ATC code: L01CD01 | L01CD51
SMILES: CC(=O)OC1C(=O)C2(C)C(O)CC3OCC3(OC(C)=O)C2C(OC(=O)c2ccccc2)C2(O)CC(OC(=O)C(O)C(NC(=O)c3ccccc3)c3ccccc3)C(C)=C1C2(C)C
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 83
Group description: Arm A: Induction* nab-Paclitaxel 125 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity.

nab-Paclitaxel: Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)

*Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².
Eligibility criteria:
Inclusion Criteria:

Histologically or cytologically confirmed HER2-negative metastatic (stage IV) breast cancer.
Measurable or non-measurable, but radiologically evaluable, disease according to RECIST 1.1 criteria.
Female aged 18 years or older.
Life expectancy > 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Either ER-positive or ER-negative disease. Patients with ER-positive disease must be endocrine resistant, defined as having failed at least one prior endocrine therapy for breast cancer, or must be candidates for first-line chemotherapy.
If previously treated with a taxane or anthracycline in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).
Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.
Normal hematologic status.
Normal renal function.
Normal liver function.
Normal cardiac function.
Women of childbearing potential: documented negative pregnancy test within 2 weeks prior to randomization, and acceptable birth control during the duration of the trial therapy and for a period of 6 months following the last administration of study drug.
Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.
Completed baseline Quality of Life Form.
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
Availability of an formalin fixed paraffin embedded (FFPE) block from the primary tumor (breast lesion) for submission to central pathology review and for translational research.
Written consent to pathology material submission, signed and dated by the patient and the Investigator prior to randomization.

Exclusion Criteria:

Any prior chemotherapy for metastatic breast cancer.
Presence of central nervous system (CNS) metastasis.
Peripheral neuropathy grade 2 or higher (CTCAE version 4).
Significant uncontrolled cardiac disease (i.e. unstable angina, recent myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.
Pregnant or lactating.
Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).
Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.
Contraindications or known hypersensitivity to the study medication or excipients.
The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment.
Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator.