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
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring 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
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Trastuzumab emtansine
Trastuzumab + docetaxel
Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.
Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m^2 IV on Day 1 of all subsequent 21-day cycles.