A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally
recurrent or metastatic disease, and candidate for chemotherapy. Patients with
measurable and non-measurable disease are eligible (locally recurrent disease must
not be amenable to resection with curative intent; patients with de novo Stage IV
disease are eligible).
- Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer
- Age ≥ 18 years.
- Left ventricular ejection fraction (LVEF) ≥ 50% at baseline (within 42 days of
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0 or 1.
- For women of childbearing potential, agreement to use an effective form of
contraception and to continue its use for the duration of study treatment and for 6
months after the last dose of study treatment.
- Signed, written informed consent obtained prior to any study procedure.
- History of anti-cancer therapy for MBC (with the exception of one prior hormonal
regimen for MBC).
- History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer
in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant
- History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting
with a disease-free interval from completion of the systemic treatment (excluding
hormonal therapy) to metastatic diagnosis of < 12 months.
- History of persistent Grade ≥ 2 hematologic toxicity resulting from previous adjuvant
- Current peripheral neuropathy of National Cancer Institute-Common Terminology
Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥ 3 at randomization.
- History of other malignancy within the last 5 years, except for carcinoma in situ of
the cervix or basal cell carcinoma.
- Current clinical or radiographic evidence of central nervous system (CNS) metastases.
- Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is
mandatory in cases of clinical suspicion of brain metastases.
- History of exposure to cumulative doses of anthracyclines.
- Current uncontrolled hypertension or unstable angina.
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA)
criteria, or serious cardiac arrhythmia requiring treatment.
- History of myocardial infarction within 6 months of randomization.
- History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant
or adjuvant therapy.
- Current dyspnea at rest due to complications of advanced malignancy, or other
diseases that require continuous oxygen therapy.
- Inadequate organ function within 28 days prior to randomization.
- Current severe, uncontrolled systemic disease.
- Major surgical procedure or significant traumatic injury within 28 days prior to
study treatment start or anticipation of the need for major surgery during the course
of study treatment.
- Pregnant or lactating women.
- History of receiving any investigational treatment within 28 days of randomization.
- Current known infection with human immunodeficiency virus (HIV), hepatitis B virus
(HBV), or hepatitis C virus (HCV).
- Receipt of intravenous (IV) antibiotics for infection within 14 days of
- Current chronic daily treatment with corticosteroids (excluding inhaled steroids).
- Known hypersensitivity to any of the study drugs.
- Assessed by the investigator to be unable or unwilling to comply with the
requirements of the protocol.