A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab emtansine
Intervention description: Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial.
Intervention MeSH terms: Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This single-arm open-label study assessed the safety, feasibility, and efficacy of
      trastuzumab emtansine (T-DM1) after the completion of anthracycline-based
      adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer.
      Patients received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17
      cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients ≥ 18 years of age.

          -  Locally advanced, inflammatory, or early stage, unilateral, and histologically
             confirmed invasive breast cancer documented at a local laboratory (patients with
             inflammatory breast cancer must be able to have a core needle biopsy).

          -  Herceptin (HER)2-positive tumor, confirmed by central testing using
             immunohistochemistry (IHC) and in situ hybridization (ISH) methods.

          -  Willingness to receive anthracycline-based chemotherapy or have received
             doxorubicin/cyclophosphamide (AC) OR 5-fluorouracil (FU)/epirubicin/ cyclophosphamide
             (FEC) in a similar dose and schedule as described in the protocol as part of
             neoadjuvant or adjuvant treatment.

          -  For women of childbearing potential and men with partners of childbearing potential,
             agreement to use a highly effective, non-hormonal form of contraception or 2 effective
             forms of non-hormonal contraception by the patient and/or partner. Contraception use
             must continue for the duration of study treatment and for at least 6 months after the
             last dose of study treatment. Male patients should use condoms for the duration of the
             study. Specific country requirements will be followed.

          -  Negative results of serum pregnancy test for premenopausal women of reproductive
             capacity and for women < 12 months after menopause.

          -  Patients may enroll before or after AC/FEC chemotherapy has completed.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Adequate hematologic, biochemistry, and cardiac assessments.

        Exclusion Criteria:

          -  Stage IV breast cancer or bilateral breast cancer.

          -  Pregnant or breastfeeding women.

          -  History of other malignancy within the previous 5 years, except contralateral breast
             cancer and ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS),
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             Stage I uterine cancer, or other cancers with outcome similar to those mentioned
             above.

          -  Radiation therapy, immunotherapy, or biotherapy within 5 years before study
             enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study
             enrollment is allowed. Patients receiving AC/FEC in a similar fashion to the study
             treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be
             allowed to enroll in the study after the completion of their AC/FEC. No other prior
             history of cardiotoxic chemotherapy is allowed.

          -  Active cardiac history.

          -  Current chronic daily treatment with oral corticosteroids or equivalent.

          -  Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.

          -  Active, unresolved infections at screening.

          -  Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus
             (HCV) infection.

          -  Major surgery within 4 weeks before enrollment that is unrelated to the breast cancer.

          -  Patients for whom concomitant radiotherapy + T-DM1 may be contraindicated yet
             radiation therapy is planned.

          -  Known hypersensitivity to any of the study drugs or derivatives, including murine
             proteins.

          -  Grade ≥ 2 peripheral neuropathy at Baseline.