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

NCT00950300 | Completed Phase 3 Results

• 2 other identifiers: BO222272008-007326-19
• Study Type: interventional
• Target: 596
• Locations: 25 countries
• Sites: 101

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

Outcome Measures

Primary Outcomes (2)

• Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery

  Pre-dose samples were obtained prior to surgery (Cycle 8). The observed Ctrough was recorded, averaged among all participants, and expressed in micrograms per milliliter (μg/mL).

  Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

• Percentage of Participants With Pathological Complete Response (pCR)

  Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR, defined as absence of neoplastic invasive cells in the breast according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.

  After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)

Secondary Outcomes (20)

• Observed Ctrough of Trastuzumab After Surgery

  Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

• Predicted Ctrough of Trastuzumab Prior to Surgery

  Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

• Predicted Ctrough of Trastuzumab After Surgery

  Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

• Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery

  Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

• Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery

  Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

Study Arms (2)

Herceptin IV + Chemotherapy

ACTIVE COMPARATOR

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.

Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Herceptin IV [trastuzumab]

Herceptin SC + Chemotherapy

EXPERIMENTAL

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.

Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Herceptin SC [trastuzumab]

Interventions

5-Fluorouracil 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.

Herceptin IV + Chemotherapy; Herceptin SC + Chemotherapy

Cyclophosphamide 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.

Herceptin IV + Chemotherapy; Herceptin SC + Chemotherapy

Docetaxel 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.

Herceptin IV + Chemotherapy; Herceptin SC + Chemotherapy

Epirubicin 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 + Chemotherapy; Herceptin SC + Chemotherapy

Herceptin IV [trastuzumab] 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 IV + Chemotherapy

Herceptin SC [trastuzumab] 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.

Herceptin SC + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (106)

Centro Medico San Roque; Oncology Dept

San Miguel de Tucumán, T4000IAK, Argentina

Location

Caipo; Oncology

San Miguel de Tucumán, T400IAK, Argentina

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital das Clinicas - UFPR; Quimioterapia

Curitiba, Paraná, 80060-900, Brazil

Location

Liga Norte Riograndense Contra O Câncer

Natal, Rio Grande do Norte, 59040150, Brazil

Location

Clinica de Neoplasias Litoral

Itajaí, Santa Catarina, 88301-220, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Hospital Perola Byington

São Paulo, São Paulo, 01317-000, Brazil

Location

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, São Paulo, 18030-245, Brazil

Location

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, H1T 2M4, Canada

Location

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Québec, G1S 4L8, Canada

Location

Hospital Universitario San Ignacio

Bogotá, 000472, Colombia

Location

Grupo Salud Coop

Bogotá, Colombia

Location

Oncólogos de Occidente

Pereira, 600004, Colombia

Location

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, 779 00, Czechia

Location

Krajska Nemocnice Pardubice Neurologicka Klinika

Pardubice, 532 03, Czechia

Location

Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni

Prague, 140 59, Czechia

Location

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

Prague, 180 81, Czechia

Location

North Estonia Medical Centre Foundation; Oncology Centre

Tallinn, 13419, Estonia

Location

Tartu University Hospital; Clinic of Hematology and Oncology

Tartu, 50406, Estonia

Location

HOPITAL JEAN MINJOZ; Oncologie

Besançon, 25030, France

Location

Institut Daniel Hollard; Chimiotherapie Ambulatoire

Grenoble, 38000, France

Location

Hopital Albert Michallon; Oncologie

La Tronche, 38700, France

Location

Centre Jean Bernard

Le Mans, 72015, France

Location

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

Paris, 75475, France

Location

Institut Jean Godinot; Hopital De Jour

Reims, 51056, France

Location

Centre Rene Huguenin; Medecine B

Saint-Cloud, 92210, France

Location

CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

Berlin, 10117, Germany

Location

Praxis Dr. Schoenegg

Berlin, 10719, Germany

Location

Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie

Bonn, 53113, Germany

Location

St. Johannes Hospital

Dortmund, 44137, Germany

Location

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

Hanover, 30177, Germany

Location

Sankt Elisabeth Krankenhaus; Gynaekology

Leipzig, 04277, Germany

Location

Klinik Lippe Lemgo; Frauenklinik

Lemgo, 32657, Germany

Location

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, 63069, Germany

Location

Klinik Obergöltzsch; Abt. Gynäkologie

Rodewisch, 08228, Germany

Location

Universitätsklinik Tübingen; Frauenklinik

Tübingen, 72076, Germany

Location

Centro Oncologico S.A.

Guatemala City, 01010, Guatemala

Location

Queen Mary Hospital; Surgery

Hong Kong, 852, Hong Kong

Location

Semmelweis Egyetem Onkologiai Központ

Budapest, 1083, Hungary

Location

Hospital of Aladar Petz; Dept of Oncoradiology

Győr, 9023, Hungary

Location

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

Szeged, 6720, Hungary

Location

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, 9112001, Israel

Location

Rabin Medical Center; Oncology Dept

Petah Tikva, 49100, Israel

Location

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

Napoli, Campania, 80131, Italy

Location

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

Cremona, Lombardy, 26100, Italy

Location

Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica

Pavia, Lombardy, 27100, Italy

Location

Fondazione Salvatore Maugeri

Pavia, Lombardy, 27100, Italy

Location

Hospital Privado San Jose; Oncologia

Obregón, 85000, Mexico

Location

Centro Oncológico Estatal; ISSSEMYM Oncología

Toluca, 50180, Mexico

Location

Centro Oncologico America

Panama City, 0834-02723, Panama

Location

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

Arequipa, 04001, Peru

Location

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

Lima, 11, Peru

Location

Oncosalud Sac; Oncología

Lima, 41, Peru

Location

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

Piura, 20011, Peru

Location

Clinica Ricardo Palma

San Isidro, Lima 27, Peru

Location

Wojewodzki Szpital Zespolony; Oddział Onkologii

Elblag, 82-300, Poland

Location

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, 20-090, Poland

Location

Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

Olsztyn, 10-513, Poland

Location

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

Warsaw, 02-781, Poland

Location

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

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

Blokhin Cancer Research Center; Combined Treatment

Moscow, 115478, Russia

Location

Moscow city oncology hospital #62 of Moscow Healthcare Department

Moscow, 143423, Russia

Location

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, 357502, Russia

Location

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

Ryazan, 390011, Russia

Location

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, 197022, Russia

Location

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, 443031, Russia

Location

Saratov Regional Clinical Hospital & Pathology Centre

Saratov, 410053, Russia

Location

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, 355045, Russia

Location

Tula Regional Oncology Dispensary

Tula, 300053, Russia

Location

GUZ Vladimir Regional Clinical Oncological Dispensary

Vladimir, 600009, Russia

Location

Vychodoslovensky onkologicky ustav

Košice, 04001, Slovakia

Location

Nzz - Oncology Outpatient Clinic

Poprad, 05801, Slovakia

Location

National Hospital; Oncotherapy Dept

Bloemfontein, 9301, South Africa

Location

Cancercare

Cape Town, 7506, South Africa

Location

Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept

Cape Town, 7506, South Africa

Location

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

Parktown, Johannesburg, 2193, South Africa

Location

Pretoria-East Hospital; 1 Sanwood Park

Pretoria, 0081, South Africa

Location

Rondebosch Oncology Centre

Rondebosch, 7700, South Africa

Location

Sandton Oncology Centre

Sandton, 2196, South Africa

Location

Gachon Medical School Gil Medical Center; Medical Oncology

Incheon, 405-760, South Korea

Location

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, 135-710, South Korea

Location

Korea University Anam Hospital; Oncology Haemotology

Seoul, 136-705, South Korea

Location

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

Seoul, 138-736, South Korea

Location

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

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

Reus, Tarragona, 43204, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

Skånes University Hospital, Skånes Department of Onclology

Lund, 22185, Sweden

Location

Akademiska sjukhuset, Onkologkliniken

Uppsala, 75185, Sweden

Location

Changhua Christian Hospital; Dept of Surgery

Changhua, 500, Taiwan

Location

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

Taipei, 112, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation-Taipei

Taoyuan District, 333, Taiwan

Location

Chulalongkorn Hospital; Medical Oncology

Bangkok, 10330, Thailand

Location

National Cancer Inst.

Bangkok, 10400, Thailand

Location

Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

Bangkok, 10400, Thailand

Location

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

Bangkok, 10700, Thailand

Location

Prince of Songkla Uni ; Unit of Medical Oncology

Songkhla, 90110, Thailand

Location

Akdeniz University Medical Faculty; Medical Oncology Department

Antalya, 07070, Turkey (Türkiye)

Location

Istanbul Uni of Medicine Faculty; Oncology Dept

Istanbul, 34390, Turkey (Türkiye)

Location

Dokuz Eylul Uni Medical Faculty; Oncology Dept

Izmir, 35340, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sıhhiye, Ankara, 06100, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 30998824 DERIVED

• 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.

  PMID: 22884505 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fluorouracil; Cyclophosphamide; Docetaxel; Epirubicin; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2009
• First Posted: July 31, 2009
• Study Start: October 16, 2009
• Primary Completion: July 12, 2011
• Study Completion: January 24, 2017
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2017

Record last verified: 2017-12

Locations

TH (5); CZ (4); DE (10); HK (1); PE (5); RU (12); HU (3); TU (4); PL (4); SE (2); GU (1); IT (4); ME (2); BR (8); SL (2); AR (2); ZA (7); KR (4); TW (4); PA (1); ES (2); CA (2); IL (2); FR (7); CO (3)