HER2-POSITIVE, LOCALLY ADVANCED, INFLAMMATORY, OR EARLY-STAGE BREAST CANCER MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients, = 18 years of age - HER2-positive breast cancer confirmed by a central laboratory - Primary tumor > 2 cm in diameter, or > 5 mm in diameter and node-positive - Eastern Cooperative Oncology Group (ECOG) performance status =1 - Baseline LVEF = 55% (measured by ECHO or MUGA) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 367 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: - Any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer - Metastatic disease (Stage IV) or bilateral breast cancer - Previous exposure to any investigational treatment within 4 weeks before the first dose of study treatment - Prior breast or non-breast malignancy within 5 years prior to study entry, except for carcinoma in situ and basal cell and squamous cell carcinoma of the skin. Patients with malignancies occurring more than 5 years prior to study entry are permitted if curatively treated. - Inadequate hematologic, renal or liver function - Pregnant or lactating women - History of congestive heart failure of any New York Heart Association (NYHA) criteria - angina requiring anti-anginal medication - history of myocardial infarction within 6 months of enrollment - serious or uncontrolled cardiac arrhythmia requiring treatment - History or evidence of poorly controlled hypertension - Severe, uncontrolled systemic disease - Positive for hepatitis B, hepatitis C or HIV infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the cardiac safety of neoadjuvant treatment with the following regimens: • ddAC-->T+ PH: Dose-dense doxorubicin and cyclophosphamide (ddAC) given every 2 weeks for four cycles with granulocyte colony-stimulating factor (G-CSF) support as needed according to local guidelines, followed by weekly paclitaxel (T) for 12 weeks, with pertuzumab and trastuzumab (PH) given every 3 weeks from the start of paclitaxel (Cohort A). • FEC-->D+ PH: 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) given every 3 weeks for four cycles, followed by docetaxel (D) given every 3 weeks for four cycles, with pertuzumab and trastuzumab (PH) given every 3 weeks from the start of docetaxel (Cohort B).;Secondary Objective: - Secondary safety objectives are to evaluate the safety profiles of the two treatment regimens during the pre-operative (neoadjuvant) and adjuvant treatment periods, including adverse events (graded according to NCI CTCAE Version 4.0), serious adverse events, laboratory abnormalities (graded according to NCI CTCAE Version 4.0), and serum levels of anti-therapeutic antibodies (ATAs) against pertuzumab. - The efficacy objectives for this study are as follows: • To make an assessment of the antitumor activity associated with each regimen, as indicated by the pCR rate (defined as eradication of invasive disease in the breast and axilla; i.e., ypT0/is ypN0, or tpCR rate) • To investigate the clinical response, event-free survival (EFS), invasive disease-free survival (iDFS), and overall survival (OS) for each treatment regimen;Primary end point(s): Cardiac safety: Incidence of left ventricular systolic dysfunction (symptomatic or asymptomatic).;Timepoint(s) of evaluation of this end point: The primary cardiac safety evaluation will occur after all patients have completed neoadjuvant therapy (or have withdrawn from the study or are lost to follow up). Cardiac safety will continue to be assessed in all patie | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To make an assessment of the antitumor activity associated with each regimen, as indicated by the pCR rate - To investigate the clinical response, event-free survival (EFS), invasive disease-free survival (iDFS), and overall survival (OS) for each treatment regimen - Safety: Incidence of adverse events ;Timepoint(s) of evaluation of this end point: Efficacy will be assessed at the time of the primary analysis and at other key timepoints: • After all patients have completed adjuvant anti-HER2 therapy (or have withdrawn from the study or are lost to follow up) • At the end of the study (5 years after the last patient was enrolled) | — |
Countries
Brazil, Canada, Denmark, France, Germany, Italy, Norway, Poland, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed