A Study of Participant Satisfaction and Safety With Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This Phase IIIb, open-label, multinational, multicenter study will evaluate the participant's satisfaction and safety with subcutaneously administered trastuzumab in participants with HER2-positive early breast cancer. Participants will receive trastuzumab 600 milligrams (mg) administered subcutaneously every 3 weeks in the adjuvant or neo-adjuvant plus adjuvant setting for 18 cycles (1 year), unless disease progression or unacceptable toxicity occurs. The trastuzumab regimen could include mono- and/or combination therapy.

Official Title
-----------------
An Open-Label, Multinational, Multicenter, Phase IIIb Study With Subcutaneous Administration of Trastuzumab in Patients With HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Trastuzumab
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Paclitaxel
* Drug: Docetaxel
* Drug: Carboplatin
* Drug: Neo-adjuvant chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Hormonal therapy will be allowed as per institutional guidelines Prior use of anti-HER2 therapy will be allowed, except for early breast cancer participants in the neo-adjuvant setting Left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 55 percent (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab, or, for those who were receiving trastuzumab when beginning the study, documented results within an acceptable limit from a cardiac assessment within 3 months prior to enrollment HER2-positive disease immunohistochemistry 3 plus (IHC3+) or in situ hybridization (ISH) positive as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast No evidence of residual, locally recurrent or metastatic disease after completion of surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant) Use of concurrent curative radiotherapy will be permitted Exclusion Criteria: History of other malignancy which could affect compliance with the protocol or interpretation of results. Participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and participants with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible Severe dyspnea at rest or requirement for supplementary oxygen therapy Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) Pregnant or lactating women Concurrent enrollment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin, or a history of severe allergic or immunological reactions, e.g. difficult to control asthma Inadequate bone marrow, hepatic or renal function

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab<br>In adjuvant setting trastuzumab will be administered in the following treatment regimens: (a) trastuzumab following surgery, chemotherapy (neo-adjuvant or adjuvant) and radiotherapy (if applicable); (b) trastuzumab following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel; (c) trastuzumab in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin. In neo-adjuvant setting, trastuzumab will be administered in combination with neo-adjuvant chemotherapy followed by adjuvant trastuzumab, for locally advanced (including inflammatory) breast cancer or tumors greater than (>) 2 centimeters (cm) in diameter. | Drug: Trastuzumab<br>* Trastuzumab will be administered subcutaneously at a fixed dose of 600 mg (irrespective of body weight) every 3 weeks for 1 year (adjuvant or neo-adjuvant plus adjuvant therapy).<br>* Other names: Herceptin;Drug: Doxorubicin<br>* Doxorubicin will be administered in combination with trastuzumab and cyclophosphamide in the adjuvant setting as per local Product Information and the investigator's discretion.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered in combination with trastuzumab and doxorubicin in the adjuvant setting as per local Product Information and the investigator's discretion.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered in combination with trastuzumab in the adjuvant setting as per local Product Information and the investigator's discretion.<br>Drug: Docetaxel<br>* Docetaxel will be administered in combination with trastuzumab in the adjuvant setting as per local Product Information and the investigator's discretion.<br>Drug: Carboplatin<br>* Carboplatin will be administered in combination with trastuzumab and docetaxel in the adjuvant setting as per local Product Information and the investigator's discretion.<br>Drug: Neo-adjuvant chemotherapy<br>* Neo-adjuvant chemotherapy will be administered according to local guidelines in combination with trastuzumab in the neo-adjuvant setting. The study protocol does not mention any specific neo-adjuvant chemotherapy drug names.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Satisfaction Questionnaire Score |  | Week 52 | 
| Percentage of Participants with Adverse Events (AEs) |  | Baseline up to 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthcare Professional Experience and Satisfaction Questionnaire Score |  | Week 52 | 
| Overall Survival (OS) |  | Baseline until death from any cause (up to 4.5 years) | 
| Disease-Free Survival (DFS) | Diagnosis of breast cancer relapse will be made based on routine clinical, radiological and laboratory criteria. Acceptable methods of confirmation of recurrence include radiology, computed tomography (CT) scan, brain scan, ultrasound, or cytology, as per local practice. In case of uncertainty, disease relapse should be confirmed by histological or cytological examination of a suspicious lesion, if possible. | Baseline until first documented disease or death, whichever comes first (up to 4.5 years) | 
| Number of Days on Trastuzumab Treatment |  | Baseline up to 1 year | 
| Total Daily Dose of Trastuzumab |  | Baseline up to 1 year | 
| Cumulative Dose of Trastuzumab |  | Baseline up to 1 year | 
| Duration of Treatment, Follow-up, and Safety Observation |  | Baseline up to 4.5 years |