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

NCT ID: NCT01401166

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 488 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-12-31

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.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

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.

Single-Use Injection Device

Intervention Type: DEVICE

The SID will be used, containing Herceptin 600 mg per 5 milliliters (mL).

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.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

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.

Single-Use Injection Device

Intervention Type: DEVICE

The SID will be used, containing Herceptin 600 mg per 5 mL.

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.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Single-Use Injection Device

The SID will be used, containing Herceptin 600 mg per 5 milliliters (mL).

Intervention Type: DEVICE

Single-Use Injection Device

The SID will be used, containing Herceptin 600 mg per 5 mL.

Intervention Type: DEVICE

Other Intervention Names

Trastuzumab; Trastuzumab

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Barrie, Ontario, Canada

Brampton, Ontario, Canada

Kitchener, Ontario, Canada

Sault Ste. Marie, Ontario, Canada

Toronto, Ontario, Canada

Saskatoon, Saskatchewan, Canada

Herning, , Denmark

Odense, , Denmark

Vejle, , Denmark

Besançon, , France

Bobigny, , France

Bordeaux, , France

Caen, , France

La Tronche, , France

LeMans, , France

Lyon, , France

Paris, , France

Rennes, , France

Saint-Cloud, , France

Strasbourg, , France

Berlin, , Germany

Deggendorf, , Germany

Essen, , Germany

Fürstenwalde, , Germany

Hamburg, , Germany

Hanover, , Germany

Magedburg, , Germany

Mainz, , Germany

Meiningen, , Germany

Recklinghausen, , Germany

Ulm, , Germany

Genoa, Liguria, Italy

Milan, Lombardy, Italy

Milan, Lombardy, Italy

Pavia, Lombardy, Italy

Antella (FI), Tuscany, Italy

Terni, Umbria, Italy

Gdansk, , Poland

Warsaw, , Poland

Irkutsk, , Russia

Kazan', , Russia

Moscow, , Russia

Orenburg, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Yekaterinburg, , Russia

Barcelona, Barcelona, Spain

Córdoba, Cordoba, Spain

Guadalajara, Guadalajara, Spain

Huesca, Huesca, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Málaga, Malaga, Spain

Oviedo, Principality of Asturias, Spain

Seville, Sevilla, Spain

Seville, Sevilla, Spain

Barakaldo, Vizcaya, Spain

Zamora, Zamora, Spain

Eskilstuna, , Sweden

Gävle, , Sweden

Jönköping, , Sweden

Sundsvall, , Sweden

Baden, , Switzerland

Zurich, , Switzerland

Adana, , Turkey (Türkiye)

Ankara, , Turkey (Türkiye)

Bornova, ?zm?r, , Turkey (Türkiye)

Gaziantep, , Turkey (Türkiye)

Brighton, , United Kingdom

Cardiff, , United Kingdom

Chelmsford, , United Kingdom

Maidstone, , United Kingdom

Nottingham, , United Kingdom

Peterborough, , United Kingdom

Truro, , United Kingdom

Countries

Canada; Denmark; France; Germany; Italy; Poland; Russia; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28963915 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28549309 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26806010 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25070545 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23965225 (View on PubMed)

Other Identifiers

2010-024099-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO22982

Identifier Type: -

Identifier Source: org_study_id