A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (PUFFIN)

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Docetaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02896855

YO29296

Details and patient eligibility

About

This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.

Enrollment: 243 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
• HER2-positive metastatic breast cancer (MBC)
• Left ventricular ejection fraction (LVEF) greater than or equal to (>=) 55 percent (%) at baseline (within 42 days of randomization)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab)

Exclusion criteria

• 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 setting
• 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 less than (<) 12 months
• History of persistent Grade >= 2 hematologic toxicity resulting from previous adjuvant therapy
• Grade >= 3 peripheral neuropathy at randomization
• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent
• Current clinical or radiographic evidence of central nervous system (CNS) 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) classification, or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months of randomization
• History of LVEF decrease to < 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 C virus (HCV), or active hepatitis B virus (HBV)
• Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization
• Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
• Known hypersensitivity to any of the protocol-specified study treatments
• Concurrent participation in an interventional or noninterventional study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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243 participants in 2 patient groups

Arm A: Placebo + Trastuzumab + Docetaxel

Active Comparator group

Description:

Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram \[mg/kg\] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter \[mg/m\^2\]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab

Drug: Placebo

Arm B: Pertuzumab + Trastuzumab + Docetaxel

Experimental group

Description:

Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m\^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Treatment:

Drug: Docetaxel

Drug: Trastuzumab

Drug: Pertuzumab