Phase III, randomized, multicenter, multinational, open label study in patients with HER2-positive primary breast cancer following neoadjuvant chemotherapy and surgery.

Phase 1

Conditions: HER2-positive primary breast cancer.
MedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002018-37-AT

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: 1486

Inclusion Criteria

• 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.
• Women of childbearing potential and men with partners of
childbearing potential must be willing to use effective contraception as
defined by protocol for the duration of study treatment and for at least 7
months after the last dose of study treatment.
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

Exclusion Criteria

• 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)
• 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 the length of time it takes for the primary breast cancer to recur after treatment with preoperative chemotherapy followed by surgery between the 2 treatment arms.;Secondary Objective: To compare the length of time it takes for:<br>• the primary breast cancer to develop in other location(s)<br>• occurrence of secondary cancers in other organs<br>• death<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 12 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 12 years<br>7. up to 3 years<br>

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