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

Phase 2

Completed

• Conditions: Breast Neoplasms
• Interventions: Drug: Herceptin; Device: Single-Use Injection Device

• Registration Number: NCT01401166
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-07-22
• Study First Submitted QC: 2011-07-22
• Study First Posted: 2011-07-25
• Study Start: 2011-10
• Primary Completion: 2013-05
• Results First Submitted: 2015-02-09
• Results First Submitted QC: 2015-06-03
• Results First Posted: 2015-06-08
• Study Completion: 2015-12
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-19
• Last Update Posted: 2017-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 488

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cohort 1: IV then SC (SID) Herceptin	Herceptin	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.
Cohort 2: IV then SC (Vial) Herceptin	Herceptin	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.
Cohort 2: SC (Vial) then IV Herceptin	Herceptin	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.
Cohort 1: SC (SID) then IV Herceptin	Herceptin	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.
Cohort 1: IV then SC (SID) Herceptin	Single-Use Injection Device	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.
Cohort 1: SC (SID) then IV Herceptin	Single-Use Injection Device	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants by Preferred Method of Drug Administration	Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of HCPs by Most Satisfied Method of Drug Administration	Week 24	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.
Percentage of HCPs by Time Required to Perform Each Method of Drug Administration	Week 24	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.
Percentage of Participants With an Event-Free Survival (EFS) Event	From Baseline until time of event; assessed every 6 months (median follow-up of 3 years)	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.
Duration of EFS According to Kaplan-Meier Estimate	From Baseline until time of event; assessed every 6 months (median follow-up of 3 years)	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.
3-Year EFS Rate	Year 3	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.
Percentage of Participants With Responses of "Agree" or "Strongly Agree" on the SC SID Satisfaction Questionnaire	Immediately following first self-administration of SC Herceptin via SID (once during Weeks 25 to 52)	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.
Percentage of Participants With Anti-Trastuzumab or Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies	Baseline, pre-dose (0 hours) during Cycle 5 (cycle length of 3 weeks)	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.