A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

NCT ID: NCT00950300

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 596 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-16
• Study Completion Date: 2017-01-24

Brief Summary

In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Herceptin IV + Chemotherapy

Participants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.

Group Type: ACTIVE_COMPARATOR

5-Fluorouracil

Intervention Type: DRUG

Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m\^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive cyclophosphamide, 500 mg/m\^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Docetaxel

Intervention Type: DRUG

Participants will receive docetaxel, 75 mg/m\^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.

Epirubicin

Intervention Type: DRUG

Participants will receive epirubicin, 75 mg/m\^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Herceptin IV [trastuzumab]

Intervention Type: DRUG

Herceptin will be administered as 8 mg/kg (loading dose during Cycle 1) and 6 mg/kg (subsequent cycles) via IV infusion on Day 1 of each 21-day cycle for a total of 18 cycles.

Herceptin SC + Chemotherapy

Participants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.

Group Type: EXPERIMENTAL

5-Fluorouracil

Intervention Type: DRUG

Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m\^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Cyclophosphamide

Intervention Type: DRUG

Participants will receive cyclophosphamide, 500 mg/m\^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Docetaxel

Intervention Type: DRUG

Participants will receive docetaxel, 75 mg/m\^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.

Epirubicin

Intervention Type: DRUG

Participants will receive epirubicin, 75 mg/m\^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Herceptin SC [trastuzumab]

Intervention Type: DRUG

Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.

Interventions

5-Fluorouracil

Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m\^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Intervention Type: DRUG

Cyclophosphamide

Participants will receive cyclophosphamide, 500 mg/m\^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Intervention Type: DRUG

Docetaxel

Participants will receive docetaxel, 75 mg/m\^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.

Intervention Type: DRUG

Epirubicin

Participants will receive epirubicin, 75 mg/m\^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.

Intervention Type: DRUG

Herceptin IV [trastuzumab]

Herceptin will be administered as 8 mg/kg (loading dose during Cycle 1) and 6 mg/kg (subsequent cycles) via IV infusion on Day 1 of each 21-day cycle for a total of 18 cycles.

Intervention Type: DRUG

Herceptin SC [trastuzumab]

Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult women greater than or equal to (≥) 18 years of age
• Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size ≥1 centimeter (cm) by ultrasound or ≥2 cm by palpation, centrally confirmed HER2-positive (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)
• At least 1 measurable lesion in breast or lymph nodes (≥1 cm by ultrasound or ≥2 cm by palpation), except for inflammatory carcinoma (T4d)
• Baseline left ventricular ejection fraction (LVEF) ≥55%
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Adequate organ function at Baseline

Exclusion Criteria

• History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
• Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix
• Metastatic disease
• Any prior therapy with anthracyclines
• Prior anti-HER2 therapy or biologic or immunotherapy
• Serious cardiac illness
• Pregnant or lactating women

• 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

Centro Medico San Roque; Oncology Dept

San Miguel de Tucumán, , Argentina

Caipo; Oncology

San Miguel de Tucumán, , Argentina

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, Brazil

Hospital das Clinicas - UFPR; Quimioterapia

Curitiba, Paraná, Brazil

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, Brazil

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, Brazil

Hospital Amaral Carvalho

Jaú, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Hospital Perola Byington

São Paulo, São Paulo, Brazil

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, São Paulo, Brazil

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, Canada

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Québec, , Canada

Hospital Universitario San Ignacio

Bogotá, , Colombia

Grupo Salud Coop

Bogotá, , Colombia

Oncólogos de Occidente

Pereira, , Colombia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

Krajska Nemocnice Pardubice Neurologicka Klinika

Pardubice, , Czechia

Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni

Prague, , Czechia

Lekarske Fakulty Univerzity Karlovy Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie

Prague, , Czechia

North Estonia Medical Centre Foundation; Oncology Centre

Tallinn, , Estonia

Tartu University Hospital; Clinic of Hematology and Oncology

Tartu, , Estonia

HOPITAL JEAN MINJOZ; Oncologie

Besançon, , France

Institut Daniel Hollard; Chimiotherapie Ambulatoire

Grenoble, , France

Hopital Albert Michallon; Oncologie

La Tronche, , France

Centre Jean Bernard

Le Mans, , France

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

Paris, , France

Institut Jean Godinot; Hopital De Jour

Reims, , France

Centre Rene Huguenin; Medecine B

Saint-Cloud, , France

CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

Berlin, , Germany

Praxis Dr. Schoenegg

Berlin, , Germany

Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie

Bonn, , Germany

St. Johannes Hospital

Dortmund, , Germany

Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding

Hanover, , Germany

Sankt Elisabeth Krankenhaus; Gynaekology

Leipzig, , Germany

Klinik Lippe Lemgo; Frauenklinik

Lemgo, , Germany

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, , Germany

Klinik Obergöltzsch; Abt. Gynäkologie

Rodewisch, , Germany

Universitätsklinik Tübingen; Frauenklinik

Tübingen, , Germany

Centro Oncologico S.A.

Guatemala City, , Guatemala

Queen Mary Hospital; Surgery

Hong Kong, , Hong Kong

Semmelweis Egyetem Onkologiai Központ

Budapest, , Hungary

Hospital of Aladar Petz; Dept of Oncoradiology

Győr, , Hungary

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, , Hungary

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, , Israel

Rabin Medical Center; Oncology Dept

Petah Tikva, , Israel

Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

Napoli, Campania, Italy

ASST DI CREMONA; Dip. Medicina - S.C. Oncologia

Cremona, Lombardy, Italy

Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica

Pavia, Lombardy, Italy

Fondazione Salvatore Maugeri

Pavia, Lombardy, Italy

Hospital Privado San Jose; Oncologia

Obregón, , Mexico

Centro Oncológico Estatal; ISSSEMYM Oncología

Toluca, , Mexico

Centro Oncologico America

Panama City, , Panama

Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology

Arequipa, , Peru

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

Lima, , Peru

Oncosalud Sac; Oncología

Lima, , Peru

Unidad de Investigacion Oncologia Clinica - Piura; Unidad de Oncología Clínica

Piura, , Peru

Clinica Ricardo Palma

San Isidro, , Peru

Wojewodzki Szpital Zespolony; Oddział Onkologii

Elblag, , Poland

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, , Poland

Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

Olsztyn, , Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, , Poland

FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF

Saint Petersburg, Sankt-Peterburg, Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Blokhin Cancer Research Center; Combined Treatment

Moscow, , Russia

Moscow city oncology hospital #62 of Moscow Healthcare Department

Moscow, , Russia

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, , Russia

SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF

Ryazan, , Russia

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, , Russia

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, , Russia

Saratov Regional Clinical Hospital & Pathology Centre

Saratov, , Russia

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, , Russia

Tula Regional Oncology Dispensary

Tula, , Russia

GUZ Vladimir Regional Clinical Oncological Dispensary

Vladimir, , Russia

Vychodoslovensky onkologicky ustav

Košice, , Slovakia

Nzz - Oncology Outpatient Clinic

Poprad, , Slovakia

National Hospital; Oncotherapy Dept

Bloemfontein, , South Africa

Cancercare

Cape Town, , South Africa

Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept

Cape Town, , South Africa

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

Parktown, Johannesburg, , South Africa

Pretoria-East Hospital; 1 Sanwood Park

Pretoria, , South Africa

Rondebosch Oncology Centre

Rondebosch, , South Africa

Sandton Oncology Centre

Sandton, , South Africa

Gachon Medical School Gil Medical Center; Medical Oncology

Incheon, , South Korea

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, , South Korea

Korea University Anam Hospital; Oncology Haemotology

Seoul, , South Korea

Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology

Seoul, , South Korea

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

Reus, Tarragona, Spain

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, , Spain

Skånes University Hospital, Skånes Department of Onclology

Lund, , Sweden

Akademiska sjukhuset, Onkologkliniken

Uppsala, , Sweden

Changhua Christian Hospital; Dept of Surgery

Changhua, , Taiwan

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Medical Foundation-Taipei

Taoyuan District, , Taiwan

Chulalongkorn Hospital; Medical Oncology

Bangkok, , Thailand

National Cancer Inst.

Bangkok, , Thailand

Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

Bangkok, , Thailand

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

Bangkok, , Thailand

Prince of Songkla Uni ; Unit of Medical Oncology

Songkhla, , Thailand

Akdeniz University Medical Faculty; Medical Oncology Department

Antalya, , Turkey (Türkiye)

Istanbul Uni of Medicine Faculty; Oncology Dept

Istanbul, , Turkey (Türkiye)

Dokuz Eylul Uni Medical Faculty; Oncology Dept

Izmir, , Turkey (Türkiye)

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sıhhiye, Ankara, , Turkey (Türkiye)

Countries

Argentina; Brazil; Canada; Colombia; Czechia; Estonia; France; Germany; Guatemala; Hong Kong; Hungary; Israel; Italy; Mexico; Panama; Peru; Poland; Russia; Slovakia; South Africa; South Korea; Spain; Sweden; Taiwan; Thailand; Turkey (Türkiye)

References

Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 May 1;5(5):e190339. doi: 10.1001/jamaoncol.2019.0339. Epub 2019 May 9.

Reference Type: DERIVED

PMID: 30998824 (View on PubMed)

Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. doi: 10.1016/S1470-2045(12)70329-7. Epub 2012 Aug 9.

Reference Type: DERIVED

PMID: 22884505 (View on PubMed)

Other Identifiers

2008-007326-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO22227

Identifier Type: -

Identifier Source: org_study_id