A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of 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
- 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.
- 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
- 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
- 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
- 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.