A Study of Trastuzumab Emtansine in Indian Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Unresectable Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Treatment With Trastuzumab and a Taxane
Condition: HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab emtansine
Intervention description: 3.6 mg/kg intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle, repeated every 3 weeks
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase IV, single-arm, multicenter, open-label clinical trial designed to assess the
      safety of trastuzumab emtansine in Indian patients with HER2-positive unresectable locally
      advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior
      treatment with trastuzumab and a taxane.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Prospectively confirmed HER2-positive (i.e., IHC 3+ or IHC 2+ and gene amplified by
             fluorescence in situ hybridization [FISH] positive) as assessed on primary tumor
             and/or metastatic site

          -  Documented progression of unresectable, locally advanced, or mBC, determined by the
             investigator

          -  Left ventricular ejection fraction (LVEF) >/= 50% by echocardiogram (ECHO)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  A negative serum Beta-Human Chorionic Gonadotropin (Beta-HCG) test for women of
             childbearing potential (premenopausal or not meeting the definition of postmenopausal
             i.e. >/= 12 months of amenorrhea), and women who have not undergone surgical
             sterilization (i.e., absence of ovaries and/or uterus)

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use two adequate non-hormonal methods of contraception,
             including at least one method with a failure rate of <1% per year, during the
             treatment period and for at least 7 months after the last dose of study drug

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures and agreement to refrain from donating sperm. With female
             partners of childbearing potential, men must remain abstinent or use a condom plus an
             additional contraceptive method that together result in a failure rate of <1% per year
             during the treatment period and for at least 7 months plus 90 days (a spermatogenesis
             cycle) after the last dose of study drug. Men must refrain from donating sperm during
             this same period. With pregnant female partners, men must remain abstinent or use a
             condom during the treatment period and for at least 7 months after the last dose of
             study drug.

        Exclusion Criteria:

          -  Prior treatment with trastuzumab emtansine

          -  Prior treatment with lapatinib or lapatinib with capecitabine or non-comparable
             biologic or biosimilar of trastuzumab

          -  Peripheral neuropathy of Grade >/= 3 per the National Cancer Institute's Common
             Terminology Criteria for Adverse Events (NCI CTCAE [version 4.03])

          -  History of other malignancy within the previous 5 years, except for appropriately
             treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine
             cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers
             with a similar curative outcome as those mentioned above

          -  History of receiving any anti-cancer drug/biologic or investigational treatment within
             21 days prior to enrollment except hormone therapy, which can be given up to 7 days
             prior to enrollment; recovery of treatment-related toxicity consistent with other
             eligibility criteria

          -  History of exposure to cumulative doses of anthracyclines, as defined in the protocol

          -  History of radiation therapy within 14 days of enrollment

          -  Brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms, as well as a history of radiation, surgery, or other therapy, including
             steroids, to control symptoms from brain metastases within 2 months (60 days) before
             enrollment

          -  CNS only disease

          -  History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF)
             with previous trastuzumab treatment

          -  History of symptomatic chronic heart failure (New York Heart Association [NYHA]
             Classes II-IV) or serious cardiac arrhythmia requiring treatment

          -  History of myocardial infarction or unstable angina within 6 months of enrollment

          -  Current dyspnea at rest due to complications of advanced malignancy or requirement for
             continuous oxygen therapy

          -  Current severe, uncontrolled systemic disease

          -  Pregnancy or lactation

          -  Concurrent, serious, uncontrolled infections or current known infection with human
             immunodeficiency virus (HIV) or active hepatitis B and/or hepatitis C. For patients
             who are known carriers of hepatitis B virus (HBV), active hepatitis B infection must
             be ruled out, based on negative serologic testing and/or determination of HBV DNA
             viral load per local guidelines

          -  Presence of conditions that could affect gastrointestinal absorption: malabsorption
             syndrome, resection of the small bowel or stomach, and ulcerative colitis

          -  History of intolerance (such as Grade 3-4 infusion reaction) or known hypersensitivity
             to trastuzumab or murine proteins or any component of the product

          -  Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol