A Study of Subcutaneous At Home Administration of Trastuzumab (Herceptin) in Participants With Human Epidermal Growth Factor Receptor 2-positive (HER2+) Early Breast Cancer (eBC)

Study Overview
=================
Brief Summary
-----------------
This single arm, multicenter study will evaluate the safety of assisted subcutaneous administration of trastuzumab in participants with HER2+ eBC. Participants who have completed the first 6 cycles of intravenous (IV) trastuzumab as part of the (neo)adjuvant treatment will be eligible to receive a further 12 cycles of trastuzumab in this study. Participants will receive IV trastuzumab at initial loading dose of 8 milligrams per kilogram (mg/kg) body weight (BW) for three-weekly (q3w) regimen and then recommended maintenance dose of 6 mg/kg BW q3w for the first 3 cycles (cycles 7-9) in hospital followed by subcutaneous (SC) administration of trastuzumab at a fixed dose of 600 mg q3w for next 3 cycles (Cycles 10-12) at hospital and SC administration of trastuzumab at a fixed dose of 600 mg q3w at home for the next 6 cycles (Cycles 13-18).

Official Title
-----------------
A Single Arm Multi-center Study Investigating the at Home Administration of Trastuzumab Subcutaneous Vial for the Treatment of Patients With HER2-positive Early Breast Cancer

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

Intervention / Treatment
-----------------
* Drug: Trastuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast HER2-positive disease immunohistochemistry (IHC)3+ or in situ hybridization (ISH) positive, in line with local reimbursement criteria and determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Hormonal therapy will be allowed as per institutional guidelines Left ventricular ejection fraction (LVEF) of greater than or equal to (>/=) 50% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC, 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 Participants have completed the first 6 cycles of trastuzumab IV as part of the (neo)adjuvant treatment No evidence of residual, locally recurrent or metastatic disease after completion of surgery and 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 patients with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible 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 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 Women of childbearing potential and male participants with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment 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 including hyaluronidase, 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

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>Participants with HER2+ eBC who completed the first 6 cycles of trastuzumab IV infusion as part of the (neo) adjuvant treatment will be included to continue to receive 12 cycles of trastuzumab to complete a total of 18 cycles of trastuzumab. Participants will receive trastuzumab IV infusion at initial loading dose of 8 mg/kg BW for q3w regimen as a part of neo adjuvant treatment before entering in the study and then recommended maintenance dose of 6 mg/kg BW q3w for the first 3 cycles (cycles 7-9) in hospital followed by SC administration of trastuzumab at a fixed dose of 600 mg q3w for next 3 cycles (Cycles 10-12) at hospital and SC administration of trastuzumab at a fixed dose of 600 mg q3w at home for the next 6 cycles (Cycles 13-18) (Each cycle=21 days). | Drug: Trastuzumab<br>* Trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w; Trastuzumab 600 mg q3w SC injection will be administered as per the schedule specified in the arm.<br>* Other names: Herceptin;|
| No Intervention: Health Care Professionals<br>Health Care Professionals (HCPs) included for polling purposes. HCPs were not enrolled in the study. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs included both serious and non- serious AEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An emergent AE was defined as occurring within 35 days after last treatment administration. | Up to 45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Modalities Assessed Using Patient Satisfaction Questionnaire 1 (PSQ1): In-Hospital | PSQ1 is a quality of care questionnaire containing 14 questions each of Sections A and B, with a total of 28 questions categorized on the opinion of participants about the clinicians, opinion of participants about the other staff and other questions. Responses to questions with section A (except question 11) were categorized to not at all, to a small extent, to a moderate extent, to a large extent, to a very large extent, Not applicable and missing. Responses to questions with section B were categorized to Not important, a little important, important, very important, of utmost importance, not applicable and missing. Responses to question 11 with section A were categorized to Yes, but not long, yes, quite long, yes, much long and missing. Participant experience with the treatment provided during the in-hospital part of the study was evaluated with PSQ1 questionnaire completed by the participant prior to the first dose of trastuzumab SC at home. | Prior (0 hour) to first trastuzumab SC administration at Cycle 13 (cycle length =21 days) | 
| Number of Participants With Modalities Assessed Using Patient Satisfaction Questionnaire 2 (PSQ2): At Home | PSQ2 is a quality of care questionnaire containing 13 questions each of Sections A and B, with a total of 26 questions categorized on the opinion of participants about the clinicians, opinion of participant about the other staff and other questions. Responses to questions with section A were categorized to Not at all, To a small extent, to a moderate extent, to a large extent, to a very large extent, Not applicable and missing. Responses to questions with section B were categorized to Not important, a little important, important, very important, of utmost importance, not applicable and missing. Participant experience with the treatment provided during the at-home part of the study was evaluated with the PSQ2 questionnaire completed by the participant prior to the fifth dose of trastuzumab SC at home. | Prior (0 hour) to fifth trastuzumab SC administration at Cycle 17 (cycle length=21 days) | 
| Participant-reported Severity of Symptoms as Assessed by Monroe Dunaway Anderson Symptom Inventory (MDASI) Questionnaire | MDASI questionnaire is used to rate the severity of 13 core items (pain, fatigue, nausea, vomiting, disturbed sleep, distress, shortness of breath, memory difficulties, lack of appetite, drowsiness, dry mouth, sadness, numbness or tingling). Participants were asked to rate the severity of each symptom at its worst using 0-10 numerical rating scales with 0 = not present and 10 = as bad as you can imagine. Total score was summed and ranged from 0 to 130, with lower scores indicating better outcome. | Prior (0 hours) to Cycles 7, 10, 13, 16 (Each cycle=21 days) | 
| Participant-reported Interference of Symptoms With Life as Assessed by MDASI Questionnaire | MDASI questionnaire is used to rate the interference of symptoms. The measure includes 6 symptom interference items which ask how much all symptoms, interfere with domains (general activity, mood, work, relations with others, walking, and enjoyment of life). Each items were rated on a 0-10 scale (0 = did not interfere; 10 = interfered completely). Lower scores indicating better outcome. Total score was summed and ranged from 0 to 50, with lower scores indicating better outcome. | Prior (0 hours) to Cycles 7, 10, 13, 16 (Each cycle=21 days) | 
| Number of Participants With Modalities Assessed Using Patient Experience Questionnaires (PEX) - Part 1:In-Hospital | PEX-Part 1 questionnaire contains 25 items to assess participant's experience on use of trastuzumab at hospital.1.Place of treatment? 2.Was it same place as for chemotherapy? 3.How long did it take to travel there? 4.How easy was travel? 5.Company required for travelling? 6.Was travelling cost a problem? 7.Considering all these,was travelling for treatment overall a problem? 8.How helpful were nursing/medical staff? 9.How pleasant was place of study? 10.How was IV treatment given? 11.If Venous Access Device(VAD),what was it? 12.Did hospital staff have difficulty inserting cannula? 13.Time for cannulation? 14.How painful was IV? 15.How much time to access port/line usually take? 16.How painful was it? 17.Time for IV sessions? 18.Anxiety level while IV treatment? 19.How would you describe IV sessions? 20.Did hospital staff have difficulty giving SC? 21.Time for SC? 22.How painful was SC? 23.Time for SC sessions? 24.Anxiety level while SC treatment? 25.How would you describe SC sessions? | Prior (0 hours) to Cycle 12 (cycle length=21 days) | 
| Number of Participants With Modalities Assessed Using PEX - Part 2: At Home | PEX - Part 2 questionnaire contains 6 items to assess the participant's experience on the use of trastuzumab SC vials at home.Participants answered the following questions: 1. Did the nursing staff ever have any difficulty giving the trastuzumab injection SC? 2. How many minutes did the injection (it) usually take? 3. How painful was this usually? 4. How long did the SC sessions usually last from arrival until departure of the nurse? 5. How anxious did having the SC treatment make you feel? 6. In general how would you describe these SC treatment sessions at home? | 1 month after end of treatment (up to 10 months) | 
| Number of Health Care Professionals With Modalities Assessed Using Health Care Professional Questionnaire (HCPEX-1) | HCPEX-1 questionnaire is used to assess health care professional's overall satisfaction and perceived time savings with trastuzumab SC vial in the hospital. The HCPEX-1 questionnaire (19 questions) was completed by the health care professionals administering the trastuzumab IV and SC in the hospital after at least 3 participants had completed the in-hospital part of the study. | Prior (0 hours) to Cycle 12 (cycle length=21 days) | 
| Disease-Free Survival (DFS) as Assessed by Routine Clinical, Radiological and Laboratory Criteria | DFS was defined as time from first study drug administration (i.e. Day 1 of Cycle 7) to local, regional or distant recurrence, contralateral breast cancer or death from any cause (whichever occurred first). Diagnosis of breast cancer relapse was made based on routine clinical, radiological and laboratory criteria. Acceptable methods of confirmation of recurrence included radiology, computerized tomography (CT) scan, brain scan, ultrasound, or cytology, as per local practice. In case of uncertainly, disease relapse was to be confirmed by histological or cytological examination of a suspicious lesion, if possible. | From start of treatment up to 45 months |