A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab emtansine; Lapatinib; Capecitabine
Intervention description: Trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle.; Lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle.; Capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.
Intervention MeSH terms: Capecitabine; Trastuzumab; Lapatinib; Maytansine; Ado-Trastuzumab Emtansine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 991.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase III, randomized, multicenter, international, 2-arm, open-label clinical trial
      designed to compare the safety and efficacy of trastuzumab emtansine (T-DM1) with that of
      capecitabine + lapatinib in participants with human epidermal growth factor receptor 2
      (HER2)-positive locally advanced or metastatic breast cancer. Participants will be treated
      until disease progression (PD), unmanageable toxicity, or study termination. Once disease
      progression is reported, all participants will be followed for survival every 3 months until
      death, loss to follow-up, withdrawal of consent, or study termination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HER2 status must be prospectively, centrally tested and be HER2-positive based on
             central laboratory assay results

          -  Histologically or cytologically confirmed invasive breast cancer

          -  Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or
             metastatic setting must include both a taxane, alone or in combination with another
             agent, and trastuzumab, alone or in combination with another agent

          -  Documented progression (which occur during or after most recent treatment or within 6
             months after completing of adjuvant therapy) of incurable, unresectable, locally
             advanced or metastatic breast cancer, defined by the investigator

          -  Measurable and/or nonmeasurable disease; participants with central nervous system-only
             disease are excluded

          -  Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either
             echocardiogram or multi-gated acquisition scan

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  For women of childbearing potential and men with partners of childbearing potential,
             agreement to use a highly effective, non-hormonal form of contraception; contraception
             use should continue for the duration of the study treatment and for at least 6 months
             after the last dose of study treatment

        Exclusion Criteria:

          -  History of treatment with trastuzumab emtansine

          -  Prior treatment with lapatinib or capecitabine

          -  Peripheral neuropathy of Grade >/= 3 per National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI-CTCAE), Version 3.0

          -  History of other malignancy within the last 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 randomization except hormone therapy, which could be given up to 7
             days prior to randomization; recovery of treatment-related toxicity consistent with
             other eligibility criteria

          -  History of radiation therapy within 14 days of randomization

          -  Brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms, as well as any history of radiation, surgery, or other therapy, including
             steroids, to control symptoms from brain metastases within 2 months (60 days) of
             randomization

          -  History of symptomatic congestive heart failure or serious cardiac arrhythmia
             requiring treatment

          -  History of myocardial infarction or unstable angina within 6 months of randomization

          -  Current dyspnea at rest due to complications of advanced malignancy or current
             requirement for continuous oxygen therapy

          -  Current severe, uncontrolled systemic disease (for example, clinically significant
             cardiovascular, pulmonary, or metabolic disease)

          -  Pregnancy or lactation

          -  Current known active infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus

          -  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) to trastuzumab

          -  Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase
             deficiency

          -  Current treatment with sorivudine or its chemically related analogs, such as brivudine