Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca.
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab; MYL- 1401O; Paclitaxel; Docetaxel
Intervention description: Trastuzumab 8mg/kg Iv over 90 minutes x 1 then Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks; MYL-1401O 8mg/kg Iv over 90 minutes x 1 then HERMyl 1401O Trastuzumab 6 mg/kg IV over 30 minutes every 3 weeks; Paclitaxel 80mg/m2 IV over 60 minutes weekly.; Docetaxel 75mg/m2 IV over 60 minutes on day 1 of a 3 week cycle
Intervention MeSH terms: Paclitaxel; Docetaxel; Trastuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 500.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      A multicenter, double-blind, randomized, parallel-group, Phase III study of the efficacy and
      safety of Hercules( Myl 1401O, Mylan Trastuzumab) plus taxane versus Herceptin® plus taxane
      as first line therapy in patients with HER2-positive metastatic breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        Locally recurrent or MBC that is not amenable to curative surgery and/or radiation.

        Documentation of HER2 gene amplification by fluorescent in situ hybridization (FISH) (as
        defined by a ratio >2.0) or documentation of HER2-overexpression by immunohistochemistry
        (IHC) (defined as IHC3+, or IHC2+ with FISH confirmation) based on the sponsor-identified
        central laboratory prior to randomization. Archival tumor tissue samples can be used.

        Pathologically confirmed breast cancer with at least one measurable metastatic target
        lesion (based on RECIST criteria, version 1.1). Bone, central nervous system (CNS), and
        skin lesions, as well as lesions that were irradiated, biopsied or had any form of local
        intervention or surgical manipulation are only to be assessed as non-target lesions.

        Patients previously treated with trastuzumab or lapatinib in the adjuvant setting are
        allowed if metastatic disease was diagnosed at least one year after the last dose of
        treatment.

        Prior treatment with hormonal agents or bisphosphonates/denosumab is allowed.
        Bisphosphonates/denosumab can be given simultaneously with study treatment but cannot start
        after randomization and is considered an indication of progressive disease (PD). Hormonal
        agents must be discontinued prior to beginning study therapy.

        Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2

          -  Serum creatinine ≤1.5 x ULN (upper limit of normal),

          -  Total bilirubin ≤1.0 x ULN (>1.0 x ULN if documented Gilbert's disease),

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x ULN,

          -  AST and/or ALT <1.5 x ULN if alkaline phosphatase >2.5 x ULN,

          -  Alkaline phosphatase >2.5 x ULN;if bone metastases present and no liver dysfunction
             present.

        Left ventricular ejection fraction (LVEF) within institutional range of normal as measured
        by multiple gated acquisition scan or echocardiogram.

        Exclusion Criteria:

        Prior systemic therapy in the metastatic disease setting. This includes: chemotherapy,
        signal transduction inhibitors (e.g., lapatinib), HER2 targeted therapy (e.g.,
        trastuzumab), or other investigational anticancer therapy.

        Prior treatment with neoadjuvant or adjuvant anthracyclines with a cumulative dose of
        doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m2.

        Patients with bone or skin as the only site of disease. Patients with skin lesions
        measurable by CT scans or MRI as only site of measurable disease are allowed.

        Surgery or radiotherapy ≤2 weeks preceding Day 1. Target lesions have to be outside the
        irradiated fields and the patient has fully recovered from surgery or radiotherapy.

        Presence of unstable angina or a history of congestive heart failure according to the New
        York Heart Association criteria, history of myocardial infarction <1 year from
        randomization, clinically significant valvular disease, serious cardiac arrhythmia
        requiring treatment, uncontrolled hypertension or known pulmonary hypertension.

        Peripheral sensory or motor neuropathy Grade 2 or higher according to the National Cancer
        Institute-Common Terminology Criteria (NCI-CTC) Version 4.03 [19].

        Any other cancer, including contralateral breast cancer, within 5 years prior to screening
        with the exception of adequately treated ductal carcinoma in situ, adequately treated
        cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the
        skin.

        Immunocompromized patients, including known seropositivity for human immunodeficiency
        virus, or current or chronic hepatitis B and/or hepatitis C infection (as detected by
        positive testing for hepatitis B surface antigen or antibody to hepatitis C virus with
        confirmatory testing).

        Complete listing of Inc/Excl. within protocol