Phase III, randomized, multicenter, multinational, open label study in patients with HER2-positive primary breast cancer following neoadjuvant chemotherapy and surgery.
- Conditions
- HER2-positive primary breast cancer.MedDRA version: 14.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 100000004864MedDRA version: 14.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-002018-37-IT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1484
• Adult patients, aged at least 18 years
• Histologically confirmed invasive breast cancer with clinical staging T1-4, N0-3, M0 (no metastasis)
• HER2-positive tumor as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
• Patients must have received at least 6 cycles with 16 weeks of prior chemotherapy in the preoperative (neoadjuvant) setting including at least 9 weeks of a taxane and 9 weeks of HER2-directed therapy which may be given concurrently
• Surgical removal of all clinically-evident disease in the breast and lymph nodes
• Pathologic evidence of residual invasive cancer following completion of preoperative chemotherapy
• ECOG performance status of 0 or 1
• Life expectancy of at least 6 months from the first dose of study treatment
• Adequate organ function as determined by the following laboratory results, within 14 days prior to randomization.
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 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 284
• Metastatic breast cancer
• History of any prior breast cancer except for lobular carcinoma in situ
• Treatment with a cumulative dose of epirubicin greater than 480mg/m2 or any other anthracycline like doxirubicin greater than 240mg/m2
• Treatment with any investigational anticancer drug within 28 days prior to commencing study treatment
• History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
• Peripheral neuropathy greater or equal to Grade 2
• Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, angina, serious cardiac arrhythmia)
• Myocardial infarction within 12 months prior to randomization
• Active liver disease like hepatitis
• Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
• For female patients, current pregnancy or lactation
• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• Currrent, serious, uncontrolled Infections or known infection with HIV.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare invasive disease-free survival (IDFS) in patients with residual invasive breast cancer after treatment with preoperative chemotherapy and HER2-directed therapy including trastuzumab followed by surgery between the 2 treatment arms;Secondary Objective: - To compare IDFS including second non-breast cancers, disease-free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI) between the 2 treatment arms.<br>- To compare side effects of the study medication between the 2 treatment arms.;Primary end point(s): Invasive disease-free survival (IDFS);Timepoint(s) of evaluation of this end point: up to 10 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. IDFS including second non-breast cancer<br>2. Disease-free survival (DFS), including second non-breast cancer or contralateral or ipsilateral ductal carcinoma in situ<br>3. Overall survival (OS)<br>4. Recurrence-free interval (RFI): time between randomization and local, regional or distant breast cancer recurrence <br>5. Distant recurrence-free interval (DRFI): time between randomization and distant breast cancer recurrence<br>6. Cardiac and overall safety: Incidence of adverse events <br>7. Quality of life: EORTC QLQ-C30, QLQ-BR23 and EQ-5D questionnaires.;Timepoint(s) of evaluation of this end point: 1 to 6. up to 13 years<br>7. up to 3 years<br>