A Safety and Tolerability Study of Assisted and Self-Administered Subcutaneous (SC) Herceptin (Trastuzumab) as Adjuvant Therapy in Early Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

Study Overview
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Brief Summary
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This multicenter, two-cohort, non-randomized, open-label study will evaluate the safety and tolerability of assisted and self-administered SC Herceptin as adjuvant therapy in participants with early HER2-positive breast cancer following tumor excision. Participants will receive Herceptin 600 milligrams (mg) SC every 3 weeks for 18 cycles, either by an assisted administration using a conventional syringe and needle/vial formulation (Cohort A) or with assisted and self-administration using a single-use injection device (SID) in selected participants (Cohort B).

Official Title
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A Phase III Prospective, Two-Cohort Non-Randomized, Multi-Centre, Multinational, Open-Label Study to Assess the Safety of Assisted- and Self-Administered Subcutaneous Trastuzumab as Therapy in Patients With Operable HER2-Positive Early Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Herceptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed early invasive HER2-positive carcinoma of the breast with no evidence of residual, locally recurrent, or metastatic disease and defined as clinical Stage I to IIIC that is eligible for treatment with Herceptin Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Screening left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55% Exclusion Criteria: Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent History of other malignancy except for curatively treated carcinoma in situ of the cervix, basal cell carcinoma, or curatively treated malignancies (other than breast cancer) where the participant has been disease-free for at least 5 years Past history of ductal carcinoma in situ treated with any systemic therapy or with radiation therapy to the ipsilateral breast where invasive cancer subsequently developed Metastatic disease Inadequate bone marrow, hepatic, or renal function Serious cardiac or cardiovascular disease including uncontrolled hypertension or history of hypertensive crisis or hypertensive encephalopathy History of severe allergic or immunological reactions, such as difficult-to-control asthma Pregnant or lactating women

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: SC Herceptin by Needle/Syringe<br>Participants will receive SC Herceptin by an assisted administration using a conventional syringe and needle/vial formulation. | Drug: Herceptin<br>* Herceptin will be given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles.<br>* Other names: Trastuzumab;|
| Experimental: Cohort B: SC Herceptin by SID<br>Participants will receive SC Herceptin with assisted and/or self-administered use of an SID. The first administration will be performed by a trained healthcare professional. If well tolerated and the participant is willing and judged competent to perform self-administration, subsequent administration of SC Herceptin may be performed by the participant. | Drug: Herceptin<br>* Herceptin will be given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles.<br>* Other names: Trastuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period | Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported. | From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year) | 
| Percentage of Participants With a Grade 3 or Higher AE During the Treatment Period | Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. AEs were graded according to National Cancer Institute Common Terminology Criteria Version 4.0. Grade 3 AEs were those considered severe or medically significant but not immediately life-threatening. Grade 4 AEs were those considered life-threatening and/or for which urgent intervention was indicated. Grade 5 AEs were those resulting in death. The percentage of participants with a Grade 3 or higher (i.e., Grade 3 to 5) AE during the treatment period was reported. | From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year) | 
| Percentage of Participants With Treatment Interruption Due to an AE | Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with SC Herceptin treatment interrupted to assess or treat AEs was reported. | From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year) | 
| Number of Herceptin Cycles Received | Participants were planned to receive a total of 18 cycles of SC Herceptin. The median number of cycles actually received was reported. | From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year) | 
| Percentage of Participants by Total Number of Herceptin Cycles Received | Participants were planned to receive a total of 18 cycles of SC Herceptin. The percentage of participants was reported by the total number of cycles actually received. Because the data are presented non-cumulatively, this table reflects participant distribution by the highest number of cycles received. | From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year) | 
| Percentage of Participants Who Received Concomitant Cancer Therapy | Concomitant cancer treatment included chemotherapy, radiotherapy, and hormone therapy administered during the study. The percentage of participants who received any of these concomitant therapies was reported. | From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years) | 
| Percentage of Participants Who Received Concomitant Non-Cancer Therapy | Concomitant non-cancer treatment included any pharmacologic interventions administered during the study other than chemotherapy, radiotherapy, or hormone therapy. The percentage of participants who received any concomitant non-cancer therapies was reported. | From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Died by Data Cutoff of 10 March 2015 | The percentage of participants who died from any cause was reported. | From Baseline to time of event (maximum follow-up approximately 3 years as of data cutoff of 10 March 2015) | 
| Percentage of Participants Who Died During the Safety Follow-up Period | The percentage of participants who died from any cause was reported during the safety follow-up period. | From Baseline to Time of Event, Safety Follow-Up Period (Up to 6 Years) | 
| Disease-Free Survival Rate | DFS is defined as the time from first dose of SC Herceptin to the first event of local, regional or distant recurrence, contralateral invasive breast cancer (including ipsilateral ductal carcinoma in situ) or death due to any cause. Time from the date of first dose to any DFS event was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date. | From Baseline to time of event (up to approximately 8 years) | 
| Overall Survival Rate | Overall survival was defined as the time from randomization to death from any cause. Time from the date of randomization to the date of death was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date. | From Baseline to Time of Event (Up to Approximately 6 Years) | 
| Percentage of Participants by Item Response to SID Satisfaction Questionnaire | The SID satisfaction questionnaire was administered twice during the study and asked participants to respond to five statements using a Likert scale from Strongly Disagree to Strongly Agree. Questionnaire items were as follows: I felt comfortable injecting the study drug by myself (Comfortable), The SID was convenient and easy to use (Easy to Use), I am confident giving myself an injection in the thigh with the SID (Confident), Taking all things into account I find self-administration using the SID satisfactory (Satisfactory), If given the opportunity I would choose to continue self-injecting the study drug using the SID in the future (Continue). Participants could only select one response per questionnaire item. There was no calculation of any score, but rather, descriptive summaries were generated by item response. The percentage of participants was reported by the response given for each item on the SID satisfaction questionnaire. | Cycle 4 (cycle length 3 weeks) and last safety follow-up (LSFU) (approximately 1 year) |