A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Neoplasm Metastasis
Intervention: Trastuzumab emtansine [Kadcyla]; Trastuzumab; Docetaxel
Intervention description: The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.; The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.; Docetaxel was given at a dose of 75 or 100 mg/m^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.
Intervention MeSH terms: Docetaxel; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2-positive breast cancer; HER2; Herceptin; Taxotere; MBC; Breast cancer; TDM1; TDM-1; HER2-positive; HER2+; HER2 positive breast cancer; HER2+ breast cancer; Armed Herceptin; Trastuzumab emtansine; Trastuzumab DM1

Summary:

      This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial
      designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the
      combination of trastuzumab and docetaxel in patients with human epidermal growth factor
      receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic
      breast cancer who have not received prior chemotherapy for metastatic disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the breast with locally
             advanced or metastatic disease, and a candidate for chemotherapy.

          -  Human epidermal growth factor receptor 2 (HER2)-positive.

          -  No prior chemotherapy for their metastatic breast cancer (MBC).

          -  Measurable disease.

          -  Age ≥ 18 years.

          -  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 whose partners are pregnant should use
             condoms for the duration of the study.

        Exclusion Criteria:

          -  History of any chemotherapy for MBC.

          -  An interval of < 6 months from the completion of cytotoxic chemotherapy in the
             neo-adjuvant or adjuvant setting until the time of metastatic diagnosis.

          -  Trastuzumab ≤ 21 days prior to randomization.

          -  Hormone therapy < 7 days prior to randomization.

          -  Current peripheral neuropathy of Grade ≥ 3.

          -  History of other malignancy within the last 5 years, except for appropriately treated
             carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
             or other cancers with a similar outcome as those previously mentioned.

          -  Previous radiotherapy for the treatment of unresectable, locally advanced or
             metastatic breast cancer is not allowed if more than 25% of marrow-bearing bone has
             been irradiated or the last fraction of radiotherapy has been administered within
             approximately 3 weeks prior to randomization.

          -  Brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms or any radiation, surgery, or other therapy to control symptoms from brain
             metastases within 2 months prior to randomization.

          -  History of exposure to the following cumulative doses of anthracyclines: Doxorubicin
             or liposomal doxorubicin > 500 mg/m^2; epirubicin > 900 mg/m^2; mitoxantrone >
             120mg/m^2 and idarubicin > 90 mg/m^2.

          -  Current unstable angina.

          -  History of symptomatic congestive heart failure, or ventricular arrhythmia requiring
             treatment.

          -  History of myocardial infarction within 6 months prior to randomization.

          -  Left ventricular ejection fraction (LVEF) below 50% within approximately 28 days prior
             to randomization.

          -  History of decreased LVEF or symptomatic congestive heart failure (CHF) with previous
             adjuvant trastuzumab treatment.

          -  Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization.

          -  Severe dyspnea at rest because of complications of advanced malignancy or requiring
             current continuous oxygen therapy.

          -  Current severe, uncontrolled systemic disease (eg, clinically significant
             cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or
             bone fractures).

          -  Major surgical procedure or significant traumatic injury within approximately 28 days
             prior to randomization or anticipation of the need for major surgery during the course
             of study treatment.

          -  Current pregnancy or lactation.

          -  History of receiving any investigational treatment within approximately 28 days prior
             to randomization.

          -  Current known infection with human immunodeficiency virus (HIV), active hepatitis B
             and/or hepatitis C virus.

          -  History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to
             trastuzumab, murine proteins, or docetaxel.

          -  Known hypersensitivity to any of the study drugs, including the excipients, or any
             drugs formulated in polysorbate 80.

          -  Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.