Schedules of Nab-Paclitaxel in Metastatic Breast Cancer
Condition: Metastatic Breastcancer
MeSH terms: Breast Neoplasms
Intervention: nab-Paclitaxel
Intervention description: 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)
Intervention MeSH terms: Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 258.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Breast; Cancer; HER2-negative Stage IV; No previous chemotherapy

Summary:

      Longer first line chemotherapy duration has recently been associated with a modest, but
      significant improvement in overall survival and a clinically meaningful and statistically
      significant improvement in progression-free survival, in metastatic breast cancer patients.
      Prolonging chemotherapy until disease progression, however, must be weighed against the
      detrimental effects of continuous chemotherapy delivery. The SNAP trial seeks to improve the
      tolerability of prolonged chemotherapy administration strategy by studying alternative
      treatment schedules, while preserving and possibly improving treatment efficacy in this
      disease setting.

      The availability of a new nanoparticle albumin-bound taxane, nab-Paclitaxel (Abraxane®),
      represents an opportunity to test this hypothesis. Nab-Paclitaxel has been developed in an
      attempt to reduce the toxicity associated with standard taxane administration (caused by the
      use of chemical solvents) while increasing antitumor efficacy.

      The SNAP randomized phase II trial evaluates three schedules of nab-Paclitaxel as prolonged
      chemotherapy administration strategy. Each of three arms will be compared to a historical
      reference of seven-month median progression-free survival (PFS) based on the most recent
      trial with docetaxel as control arm to determine whether any of the three arms are worthy of
      further investigation.
    

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.