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

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)

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Herceptin; Drug: Herceptin; Device: Single-Use Injection Device; Device: Single-Use Injection Device

• Study Type: Interventional
• Enrollment (Actual): 488
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
    • Brampton, Ontario, Canada, L6R 3J7
    • Kitchener, Ontario, Canada, N2G 1G3
    • Sault Ste Marie, Ontario, Canada, P6A 2C4
    • Toronto, Ontario, Canada, M4N 3M5
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
• Denmark
  • Herning, Denmark, 7400
  • Odense, Denmark, 5000
  • Vejle, Denmark, 7100
• France
  • Besancon, France, 25030
  • Bobigny, France, 93009
  • Bordeaux, France, 33076
  • Caen, France, 14076
  • La Tronche, France, 38700
  • LeMans, France, 72000
  • Lyon, France, 69373
  • Paris, France, 75970
  • Rennes, France, 35042
  • St Cloud, France, 92210
  • Strasbourg, France, 67065
• Germany
  • Berlin, Germany, 10713
  • Deggendorf, Germany, 94469
  • Essen, Germany, 45136
  • Fuerstenwalde, Germany, 15517
  • Hamburg, Germany, 20246
  • Hannover, Germany, 30625
  • Magedburg, Germany, 39104
  • Mainz, Germany, 55131
  • Meiningen, Germany, 98617
  • Recklinghausen, Germany, 45657
  • Ulm, Germany, 89073
• Italy
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20141
    • Pavia, Lombardia, Italy, 27100
  • Toscana
    • Antella (FI), Toscana, Italy, 50011
  • Umbria
    • Terni, Umbria, Italy, 05100
• Poland
  • Gdansk, Poland, 80-952
  • Warszawa, Poland, 02-781
• Russian Federation
  • Ekaterinburg, Russian Federation, 620905
  • Irkutsk, Russian Federation, 664035
  • Kazan, Russian Federation, 420029
  • Moscow, Russian Federation, 115478
  • Orenburg, Russian Federation, 460021
  • Saint-Petersburg, Russian Federation, 197758
  • St Petersburg, Russian Federation
• Spain
  • Barcelona, Spain, 08024
  • Cordoba, Spain, 14004
  • Guadalajara, Spain, 19002
  • Huesca, Spain, 22004
  • Madrid, Spain, 28046
  • Madrid, Spain, 28905
  • Malaga, Spain, 29010
  • Sevilla, Spain, 41014
  • Sevilla, Spain, 41009
  • Zamora, Spain, 49021
  • Asturias
    • Oviedo, Asturias, Spain, 33006
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
• Sweden
  • Eskilstuna, Sweden, 63188
  • Gävle, Sweden, 80187
  • Jonkoping, Sweden, 55185
  • Sundsvall, Sweden, 85186
• Switzerland
  • Baden, Switzerland, 5405
  • Zürich, Switzerland, 8008
• Turkey
  • Adana, Turkey, 01120
  • Ankara, Turkey, 06018
  • Bornova, ?ZM?R, Turkey, 35100
  • Gaziantep, Turkey, 27310
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
  • Cardiff, United Kingdom, CF14 2TL
  • Chelmsford, United Kingdom, CM1 7ET
  • Maidstone, United Kingdom, ME16 9QQ
  • Nottingham, United Kingdom, NG5 1PB
  • Peterborough, United Kingdom, PE3 6DA
  • Truro, United Kingdom, TR1 3LJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: SC (SID) then IV 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.	Drug: Herceptin; 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.; Other Names: Trastuzumab; Drug: Herceptin; 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.; Other Names: Trastuzumab; Device: Single-Use Injection Device; The SID will be used, containing Herceptin 600 mg per 5 milliliters (mL).; Device: Single-Use Injection Device; The SID will be used, containing Herceptin 600 mg per 5 mL.
Experimental: Cohort 1: IV then SC (SID) 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.	Drug: Herceptin; 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.; Other Names: Trastuzumab; Drug: Herceptin; 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.; Other Names: Trastuzumab; Device: Single-Use Injection Device; The SID will be used, containing Herceptin 600 mg per 5 milliliters (mL).; Device: Single-Use Injection Device; The SID will be used, containing Herceptin 600 mg per 5 mL.
Experimental: Cohort 2: SC (Vial) then IV 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.	Drug: Herceptin; 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.; Other Names: Trastuzumab; Drug: Herceptin; 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.; Other Names: Trastuzumab
Experimental: Cohort 2: IV then SC (Vial) 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.	Drug: Herceptin; 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.; Other Names: Trastuzumab; Drug: Herceptin; 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.; 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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Pivot X, Verma S, Fallowfield L, Muller V, Lichinitser M, Jenkins V, Sanchez Munoz A, Machackova Z, Osborne S, Gligorov J; PrefHer Study Group. Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study. Eur J Cancer. 2017 Nov;86:82-90. doi: 10.1016/j.ejca.2017.08.019. Epub 2017 Sep 28.
• Gligorov J, Curigliano G, Muller V, Knoop A, Jenkins V, Verma S, Osborne S, Lauer S, Machackova Z, Fallowfield L, Pivot X. Switching between intravenous and subcutaneous trastuzumab: Safety results from the PrefHer trial. Breast. 2017 Aug;34:89-95. doi: 10.1016/j.breast.2017.05.004. Epub 2017 May 23.
• De Cock E, Pivot X, Hauser N, Verma S, Kritikou P, Millar D, Knoop A. A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer. Cancer Med. 2016 Mar;5(3):389-97. doi: 10.1002/cam4.573. Epub 2016 Jan 25.
• Pivot X, Gligorov J, Muller V, Curigliano G, Knoop A, Verma S, Jenkins V, Scotto N, Osborne S, Fallowfield L; PrefHer Study Group. Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study. Ann Oncol. 2014 Oct;25(10):1979-1987. doi: 10.1093/annonc/mdu364. Epub 2014 Jul 28.
• Pivot X, Gligorov J, Muller V, Barrett-Lee P, Verma S, Knoop A, Curigliano G, Semiglazov V, Lopez-Vivanco G, Jenkins V, Scotto N, Osborne S, Fallowfield L; PrefHer Study Group. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study. Lancet Oncol. 2013 Sep;14(10):962-70. doi: 10.1016/S1470-2045(13)70383-8. Epub 2013 Aug 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 22, 2011
• First Submitted That Met QC Criteria: July 22, 2011
• First Posted (Estimate): July 25, 2011

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: MO22982; 2010-024099-25 (EudraCT Number)