Participant Preference of Subcutaneous (SC) Versus Intravenous (IV) Herceptin (Trastuzumab) in Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This randomized, open-label, crossover study will evaluate participants' preference and healthcare professional (HCP) satisfaction with SC versus IV Herceptin administration in HER2-positive early breast cancer. Participants will be randomized to receive either SC Herceptin or IV Herceptin every 3 weeks for Cycles 1 to 4, followed by crossover to the other treatment administration for Cycles 5 to 8. For up to 10 additional cycles (for a total of 18 cycles), participants will receive IV or SC Herceptin every 3 weeks.

Official Title
-----------------
A Randomized, Multi-Center Cross-Over Study to Evaluate Patient Preference and Health Care Professional (HCP) Satisfaction With Subcutaneous (SC) Administration of Trastuzumab in HER2-Positive Early Breast Cancer (EBC)

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Drug: Herceptin
* Drug: Herceptin
* Device: Single-Use Injection Device
* Device: Single-Use Injection Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed HER2-positive primary breast cancer No evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy (neo-adjuvant or adjuvant) Completed neo-adjuvant chemotherapy prior to entry, if received At least 8 remaining cycles out of the total 18 planned 3-week cycles, if received IV Herceptin Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: History of other malignancy, except for ductal carcinoma in situ of the breast, curatively treated carcinoma in situ of the cervix, basal cell carcinoma, or other curatively treated malignancies of which the participant has been disease-free for at least 5 years Inadequate bone marrow function Impaired liver function Inadequate renal function Serious cardiovascular disease Human immunodeficiency virus or hepatitis B or C infection Prior maximum cumulative dose of doxorubicin greater than (>) 360 milligrams per meter-squared (mg/m^2) or epirubicin >720 mg/m^2 or equivalent

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

Sexes Eligible for Study
-----------------
Female

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

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

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: SC (SID) then IV Herceptin<br>Participants will receive Herceptin on Day 1 of each 3-week cycle for 18 cycles. During Cycles 1 to 4 of the crossover period, SC Herceptin will be administered via single-use injection device (SID), and during Cycles 5 to 8, IV Herceptin will be given. In the continuation period, participants will receive IV Herceptin for up to 10 remaining cycles. Administration will be performed by HCP. Those with at least 2 treatment cycles remaining of the 18-cycle treatment course after the crossover period will be offered the opportunity to self-administer SC Herceptin via SID under the direction of a trained HCP. | Drug: Herceptin<br>* Herceptin will be given on Day 1 of each 3-week cycle for a total of 18 cycles. If study treatment for Cycle 1 is IV Herceptin, the initial dose will be a loading dose of 8 milligrams per kilogram (mg/kg) for de novo participants who start Herceptin treatment in the study. For all other cycles where IV Herceptin is given and for non-de novo participants, the dose will be 6 mg/kg. The SC dose will be 600 milligrams (mg) for both the SID and vial formulations for all cycles where SC Herceptin is given.<br>* Other names: Trastuzumab;Device: Single-Use Injection Device<br>* The SID will be used, containing Herceptin 600 mg per 5 milliliters (mL).<br>|
| Experimental: Cohort 1: IV then SC (SID) Herceptin<br>Participants will receive Herceptin on Day 1 of each 3-week cycle for 18 cycles. During Cycles 1 to 4 of the crossover period, IV Herceptin will be given, and during Cycles 5 to 8, SC Herceptin will be administered via SID. In the continuation period, participants will receive IV Herceptin for up to 10 remaining cycles. Administration will be performed by HCP. Those with at least 2 treatment cycles remaining of the 18-cycle treatment course after the crossover period will be offered the opportunity to self-administer SC Herceptin via SID under the direction of a trained HCP. | Drug: Herceptin<br>* Herceptin will be given on Day 1 of each 3-week cycle for a total of 18 cycles. If study treatment for Cycle 1 is IV Herceptin, the initial dose will be a loading dose of 8 mg/kg for de novo participants who start Herceptin treatment in the study. For all other cycles where IV Herceptin is given and for non-de novo participants, the dose will be 6 mg/kg. The SC dose will be 600 mg for both the SID and vial formulations for all cycles where SC Herceptin is given.<br>* Other names: Trastuzumab;Device: Single-Use Injection Device<br>* The SID will be used, containing Herceptin 600 mg per 5 mL.<br>|
| Experimental: Cohort 2: SC (Vial) then IV Herceptin<br>Participants will receive Herceptin on Day 1 of each 3-week cycle for 18 cycles. During Cycles 1 to 4 of the crossover period, SC Herceptin will be administered via handheld syringe using the vial formulation, and during Cycles 5 to 8, IV Herceptin will be given. In the continuation period, participants will receive SC Herceptin via handheld syringe using the vial formulation for up to 10 remaining cycles. Administration will be performed by HCP throughout the study. | Drug: Herceptin<br>* Herceptin will be given on Day 1 of each 3-week cycle for a total of 18 cycles. If study treatment for Cycle 1 is IV Herceptin, the initial dose will be a loading dose of 8 mg/kg for de novo participants who start Herceptin treatment in the study. For all other cycles where IV Herceptin is given and for non-de novo participants, the dose will be 6 mg/kg. The SC dose will be 600 mg for both the SID and vial formulations for all cycles where SC Herceptin is given.<br>* Other names: Trastuzumab;|
| Experimental: Cohort 2: IV then SC (Vial) Herceptin<br>Participants will receive Herceptin on Day 1 of each 3-week cycle for 18 cycles. During Cycles 1 to 4 of the crossover period, IV Herceptin will be given, and during Cycles 5 to 8, SC Herceptin will be administered via handheld syringe using the vial formulation. In the continuation period, participants will receive SC Herceptin via handheld syringe using the vial formulation for up to 10 remaining cycles. Administration will be performed by HCP throughout the study. | Drug: Herceptin<br>* Herceptin will be given on Day 1 of each 3-week cycle for a total of 18 cycles. If study treatment for Cycle 1 is IV Herceptin, the initial dose will be a loading dose of 8 mg/kg for de novo participants who start Herceptin treatment in the study. For all other cycles where IV Herceptin is given and for non-de novo participants, the dose will be 6 mg/kg. The SC dose will be 600 mg for both the SID and vial formulations for all cycles where SC Herceptin is given.<br>* Other names: Trastuzumab;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants by Preferred Method of Drug Administration | The preferred method of drug administration (IV or SC Herceptin) was assessed in trial-specific telephone interviews with each study participant. Participants were asked, All things considered, which method of administration did you prefer? at the end of the crossover period (Week 24). The percentage of participants who preferred each method of drug administration was reported. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HCPs by Most Satisfied Method of Drug Administration | The method of drug administration with which HCPs were most satisfied (IV or SC Herceptin) was assessed via questionnaire with each HCP using the question, All things considered, with which method of administration were you most satisfied? at the end of the crossover period (Week 24). The percentage of HCPs who were most satisfied with each method of drug administration was reported. | Week 24 | 
| Percentage of HCPs by Time Required to Perform Each Method of Drug Administration | The time required to perform each method of drug administration was assessed via questionnaire with each HCP by asking to rate the amount of time it took to administer each method of drug administration (IV or SC Herceptin) at the end of the crossover period (Week 24). Time was rated in the following time block categories: less than (<) 5 minutes, 6 to 10 minutes, 11 to 15 minutes, 16 to 20 minutes, and greater than (>) 20 minutes. Responses of Not Sure and Unknown were also allowed. The percentage of HCPs who rated the amount of time in each of the categories was reported. | Week 24 | 
| Percentage of Participants With an Event-Free Survival (EFS) Event | EFS events included local, regional, or distant recurrence of the original breast cancer, occurrence of contralateral breast cancer, or death due to any cause. The percentage of participants who had an EFS event at any time on study was reported. | From Baseline until time of event; assessed every 6 months (median follow-up of 3 years) | 
| Duration of EFS According to Kaplan-Meier Estimate | EFS was defined as the time from randomization to a local, regional, or distant recurrence of the original breast cancer, occurrence of contralateral breast cancer, or death due to any cause. The median duration of EFS and corresponding 95 percent (%) CI according to Kaplan-Meier estimates were planned to be reported and expressed in months. | From Baseline until time of event; assessed every 6 months (median follow-up of 3 years) | 
| 3-Year EFS Rate | EFS events included local, regional, or distant recurrence of the original breast cancer, occurrence of contralateral breast cancer, or death due to any cause. The proportion of participants without an EFS event (i.e., the EFS rate) and corresponding 95% CI at 3 years after randomization was reported. | Year 3 | 
| Percentage of Participants With Responses of Agree or Strongly Agree on the SC SID Satisfaction Questionnaire | Participants who performed self-administration of SC Herceptin via SID were given an evaluation questionnaire during the continuation period (Weeks 25 to 52) after their first self-administration. Participants responded to 5 statements about their comfort with self-injection, the convenience of the SID, their self-confidence using the SID, their satisfaction with the SID, and whether they would consider using the SID again in the future. Each statement used a 5-item rating scale with responses from Strongly Disagree to Strongly Agree. The percentage of participants with a positive response (either Agree or Strongly Agree) to each questionnaire statement was reported. | Immediately following first self-administration of SC Herceptin via SID (once during Weeks 25 to 52) | 
| Percentage of Participants With Anti-Trastuzumab or Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies | Participants in Cohort 1 provided blood samples for immunogenicity testing to assess for anti-drug antibodies (ADAs) to trastuzumab or rHuPH20, a component of the SC Herceptin formulation. The percentage of participants who were trastuzumab ADA-positive and the percentage of participants who were rHuPH20 ADA-positive were each reported. | Baseline, pre-dose (0 hours) during Cycle 5 (cycle length of 3 weeks) |