A Study to Investigate the Tolerability of Subcutaneous (SC) Trastuzumab Administration in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Early Breast Cancer (eBC) Using Either a Single-Use Injection Device or Manual Administration

Study Overview
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Brief Summary
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This multicenter study in participants with HER2-positive eBC will investigate participants' pain and discomfort of SC trastuzumab (Herceptin) administered either via a single-use injection device (SID) or via vial for manual administration using a hand-held syringe (SC vial). In total, participants will obtain at least 18 cycles/1 year of trastuzumab (4 cycles of intravenous [IV] and 14 cycles of SC trastuzumab).

Official Title
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An Open-Label, Randomized, Cross-Over, Multicenter, Phase IIIb Study, to Assess Patients' Tolerability of Trastuzumab Administrated Subcutaneously (SC) Either Via a Single Use Injection Device (SID) or Via Vial for Manual Administration (SC Vial) in Patients With HER2-Positive Early Breast Cancer (eBC)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab
* Drug: Paclitaxel
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Hormonal therapy allowed as per institutional guidelines Left ventricular ejection fraction (LVEF) of greater than or equal to (>/=) 55 percent (%) measured by echocardiography (ECHO) prior to first dose of trastuzumab HER2-positive disease immunohistochemistry (IHC) 3+ 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) Participants who have completed all (neo)adjuvant treatment or participants after adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC) to whom the 4 subsequent cycles of trastuzumab in combination with paclitaxel or docetaxel are indicated per local practice Not more than 3 months should have elapsed since the last dose of adjuvant chemotherapy in case of subsequent treatment scheme Exclusion Criteria: Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent History of other malignancy that can 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. Participants with previous ductal carcinoma in situ (DCIS) of the breast are also eligible for the study Participants with severe dyspnea at rest or requiring supplementary oxygen therapy Participants with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness Prior maximum cumulative dose of doxorubicin >360 mg/m2 or maximum cumulative dose of epirubicin >720 mg/m2 or equivalent 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 anticancer 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 the adhesive of the SC device, or a history of severe allergic or immunological reactions, e.g., difficult to control asthma Inadequate bone marrow, hepatic, or renal function Major surgical procedure or significant traumatic injury within 14 days prior to the first dose of study treatment or anticipated need for major surgery during the course of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-Randomization (Trastuzumab IV)<br>Trastuzumab IV will be given during the first 4 cycles for all participants before randomization for SC administration. A dose of 6 milligrams per kilogram (mg/kg) will be given every 3 weeks. All the participants will require a loading dose on Day 1 of Cycle 1, so they will receive 8 mg/kg followed by 6 mg/kg, 3 weeks later and then 3-weekly. Concurrent administration during the first 4 cycles of trastuzumab IV with paclitaxel/docetaxel will have to be performed in accordance with local hospital practice. | Drug: Trastuzumab<br>* Trastuzumab IV or SC will be administered as described.<br>* Other names: Herceptin;Drug: Paclitaxel<br>* Paclitaxel will be administered in accordance with local hospital practice.<br>Drug: Docetaxel<br>* Docetaxel will be administered in accordance with local hospital practice.<br>|
| Experimental: Group A: Trastuzumab SC (First Vial Formulation, then SID)<br>Participants will receive 7 cycles of SC trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation) followed by 7 cycles of SC trastuzumab 600 mg SID administration after cross-over. | Drug: Trastuzumab<br>* Trastuzumab IV or SC will be administered as described.<br>* Other names: Herceptin;|
| Experimental: Group B: Trastuzumab SC (First SID, then Vial Formulation)<br>Participants will start with 7 cycles of SC trastuzumab 600 mg administration via SID and after cross-over will receive 7 injections of trastuzumab 600 mg with assisted administration using a conventional syringe and needle (SC vial formulation). | Drug: Trastuzumab<br>* Trastuzumab IV or SC will be administered as described.<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Pain as Measured on a 10 Centimeter (cm) Visual Analogue Scale |  | Week 13 up to Week 52 | 
| Participant Discomfort as Measured on a 10 cm Visual Analogue Scale |  | Week 13 up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthcare Professional Satisfaction With SC Formulation as Assessed by Health Care Professional Questionnaire (HCPQ) |  | Week 22 | 
| Patient Satisfaction With SC Formulation as Assessed by Patients Satisfaction Questionnaire (PSQ) |  | Week 52 | 
| Healthcare Professional Perceived Time Savings With SC Trastuzumab as Assessed by HCPQ |  | Week 22 | 
| Percentage of Participants With Adverse Events |  | Baseline up to approximately 3 years | 
| Overall Survival |  | From first study treatment to death from any cause, assessed up to approximately 4.5 years | 
| Disease-Free Survival, Assessed as per Institutional Practice or American Society of Clinical Oncology (ASCO) Adjuvant Follow-up Guidelines 2006 |  | From first study treatment to documented disease progression or death, assessed up to approximately 3 years | 
| Number of Days on Trastuzumab Treatment |  | Week 1 up to Week 52 | 
| Total Daily Dose of Trastuzumab |  | Week 1 up to Week 52 | 
| Cumulative Dose of Trastuzumab |  | Week 1 up to Week 52 | 
| Duration of Treatment |  | Week 1 up to Week 52 | 
| Duration of Safety Observation |  | 28 days after last study treatment (up to Week 56) | 
| Duration of Follow-Up |  | 25 months after last study treatment (up to 3 years) |