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

• ClinicalTrials.gov Identifier: NCT00950300
• Recruitment Status: Completed
• First Posted: July 31, 2009
• Results First Posted: January 23, 2017
• Last Update Posted: January 23, 2018
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Herceptin IV [trastuzumab]; Drug: Herceptin SC [trastuzumab]	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 596 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized Open-Label Study to Compare the Pharmacokinetics, Efficacy, and Safety of Subcutaneous (SC) Trastuzumab With Intravenous (IV) Trastuzumab Administered in Women With HER2-Positive Early Breast Cancer (EBC)
• Actual Study Start Date: October 16, 2009
• Actual Primary Completion Date: July 12, 2011
• Actual Study Completion Date: January 24, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: 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.; 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.; 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.; 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.; 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.
Experimental: 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.	Drug: 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.; 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.; 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.; 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.; 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.

Outcome Measures

Primary Outcome Measures :

1. Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   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).
2. Percentage of Participants With Pathological Complete Response (pCR) [ Time Frame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline) ]
   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.

Secondary Outcome Measures :

1. Observed Ctrough of Trastuzumab After Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
   Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL.
2. Predicted Ctrough of Trastuzumab Prior to Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   Predicted Ctrough at pre-dose prior to surgery (Cycle 8) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
3. Predicted Ctrough of Trastuzumab After Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
   Predicted Ctrough at pre-dose after surgery (Cycle 13) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
4. Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough >20 μg/mL was reported.
5. Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
   Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough >20 μg/mL was reported.
6. Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   PK samples were obtained prior to surgery (Cycle 7). The Cmax during Cycle 7 was recorded, averaged among all participants, and expressed in μg/mL.
7. Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days.
8. Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days) ]
   PK samples were obtained prior to surgery (Cycle 7). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 7 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in days multiplied by micrograms per milliliters (d*μg/mL).
9. Cmax of Trastuzumab After Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
   PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL.
10. Tmax of Trastuzumab After Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
    PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days.
11. AUC21d of Trastuzumab After Surgery [ Time Frame: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days) ]
    PK samples were obtained after surgery (Cycle 12). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 12 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in d*μg/mL.
12. Percentage of Participants With Total Pathological Complete Response (tpCR) [ Time Frame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline) ]
    Participants were evaluated following eight cycles of treatment and after surgery to assess for tpCR, defined as absence of neoplastic invasive cells in the breast and axillary lymph nodes according to pathologist examination. The percentage of participants with tpCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
13. Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline [ Time Frame: Tumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall) ]
    Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm) with no prior assessment of progressive disease (PD). PR was defined as greater than or equal to (≥) 30% decrease from Baseline in sum diameter (SD) of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. The percentage of participants with overall response of CR or PR at the end of neoadjuvant treatment was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
14. Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline [ Time Frame: Tumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall) ]
    Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm with no prior assessment of PD. PR was defined as ≥30% decrease from Baseline in SD of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. Time to response was defined as the time from first dose of study medication to the first assessment of CR or PR, which was the date the response was first documented by objective evidence, among participants with an overall response of CR or PR.
15. Percentage of Participants Who Experienced a Protocol-Defined Event [ Time Frame: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]
    Protocol-defined events included disease recurrence/progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. The percentage of participants who experienced a protocol-defined event at any time during the study was reported.
16. Event-Free Survival (EFS) [ Time Frame: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]
    Protocol-defined events included disease recurrence or progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. EFS was estimated by Kaplan-Meier analysis and defined as the time from randomization to the first protocol-defined event.
17. Percentage of Participants Who Died [ Time Frame: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]
    The percentage of participants who died at any time during the study was reported.
18. Overall Survival (OS) [ Time Frame: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall) ]
    OS was estimated by Kaplan-Meier analysis and defined as the time from randomization to death from any cause.
19. Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab [ Time Frame: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18 ]
    Participants provided PK samples for evaluation of anti-trastuzumab antibodies. The number of participants with "Treatment-induced ADAs" and "Treatment-enhanced ADA" against trastuzumab at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer).
20. Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20) [ Time Frame: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18 ]
    Participants in the Herceptin SC arm provided PK samples for evaluation of anti-rHuPH20 antibodies. The number of participants with "Treatment-induced ADAs" and "Treatment-enhanced ADA" against rHuPH20 (an excipient unique to the SC formulation) at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer).

Eligibility Criteria

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

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

Contacts and Locations

Locations

Argentina

Centro Medico San Roque; Oncology Dept

Tucuman, Argentina, T4000IAK

Caipo; Oncology

Tucuman, Argentina, T400IAK

Brazil

Hospital Sao Rafael - HSR

Salvador, BA, Brazil, 41253-190

Hospital das Clinicas - UFPR; Quimioterapia

Curitiba, PR, Brazil, 80060-900

Liga Norte Riograndense Contra O Câncer

Natal, RN, Brazil, 59040150

Clinica de Neoplasias Litoral

Itajai, SC, Brazil, 88301-220

Hospital Amaral Carvalho

Jau, SP, Brazil, 17210-080

Instituto do Cancer do Estado de Sao Paulo - ICESP

Sao Paulo, SP, Brazil, 01246-000

Hospital Perola Byington

Sao Paulo, SP, Brazil, 01317-000

Instituto de Oncologia de Sorocaba - CEPOS

Sorocaba, SP, Brazil, 18030-245

Canada, Quebec

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, Canada, H1T 2M4

Canada

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Quebec, Canada, G1S 4L8

Colombia

Hospital Universitario San Ignacio

Bogota, Colombia, 000472

Grupo Salud Coop

Bogota, Colombia

Oncólogos de Occidente

Pereira, Colombia, 600004

Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, Czechia, 779 00

Krajska Nemocnice Pardubice Neurologicka Klinika

Pardubice, Czechia, 532 03

Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni

Praha, Czechia, 140 59

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

Praha, Czechia, 180 81

Estonia

North Estonia Medical Centre Foundation; Oncology Centre

Tallinn, Estonia, 13419

Tartu University Hospital; Clinic of Hematology and Oncology

Tartu, Estonia, 50406

France

HOPITAL JEAN MINJOZ; Oncologie

Besancon, France, 25030

Institut Daniel Hollard; Chimiotherapie Ambulatoire

Grenoble, France, 38000

Hopital Albert Michallon; Oncologie

La Tronche, France, 38700

Centre Jean Bernard

Le Mans, France, 72015

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

Paris, France, 75475

Institut Jean Godinot; Hopital De Jour

Reims, France, 51056

Centre Rene Huguenin; Medecine B

St Cloud, France, 92210

Germany

CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

Berlin, Germany, 10117

Praxis Dr. Schoenegg

Berlin, Germany, 10719

Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie

Bonn, Germany, 53113

St. Johannes Hospital

Dortmund, Germany, 44137

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

Hannover, Germany, 30177

Sankt Elisabeth Krankenhaus; Gynaekology

Leipzig, Germany, 04277

Klinik Lippe Lemgo; Frauenklinik

Lemgo, Germany, 32657

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, Germany, 63069

Klinik Obergöltzsch; Abt. Gynäkologie

Rodewisch, Germany, 08228

Universitätsklinik Tübingen; Frauenklinik

Tübingen, Germany, 72076

Guatemala

Centro Oncologico S.A.

Guatemala, Guatemala, 01010

Hong Kong

Queen Mary Hospital; Surgery

Hong Kong, Hong Kong, 852

Hungary

Semmelweis Egyetem Onkologiai Központ

Budapest, Hungary, 1083

Hospital of Aladar Petz; Dept of Oncoradiology

Gyor, Hungary, 9023

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

Szeged, Hungary, 6720

Israel

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, Israel, 9112001

Rabin Medical Center; Oncology Dept

Petach Tikva, Israel, 49100

Italy

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

Napoli, Campania, Italy, 80131

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

Cremona, Lombardia, Italy, 26100

Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica

Pavia, Lombardia, Italy, 27100

Fondazione Salvatore Maugeri

Pavia, Lombardia, Italy, 27100

Korea, Republic of

Gachon Medical School Gil Medical Center; Medical Oncology

Incheon, Korea, Republic of, 405-760

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, Korea, Republic of, 135-710

Korea University Anam Hospital; Oncology Haemotology

Seoul, Korea, Republic of, 136-705

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

Seoul, Korea, Republic of, 138-736

Mexico

Hospital Privado San Jose; Oncologia

Obregon, Mexico, 85000

Centro Oncológico Estatal; ISSSEMYM Oncología

Toluca, Mexico, 50180

Panama

Centro Oncologico America

Panama, Panama, 0834-02723

Peru

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

Arequipa, Peru, 04001

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

Lima, Peru, 11

Oncosalud Sac; Oncología

Lima, Peru, 41

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

Piura, Peru, 20011

Clinica Ricardo Palma

San Isidro, Peru, Lima 27

Poland

Wojewodzki Szpital Zespolony; Oddział Onkologii

Elblag, Poland, 82-300

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, Poland, 20-090

Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

Olsztyn, Poland, 10-513

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

Warszawa, Poland, 02-781

Russian Federation

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

St Petersburg, Leningrad, Russian Federation, 197758

Ivanovo Regional Oncology Dispensary

Ivanovo, Russian Federation, 153040

Blokhin Cancer Research Center; Combined Treatment

Moscow, Russian Federation, 115478

Moscow city oncology hospital #62 of Moscow Healthcare Department

Moscow, Russian Federation, 143423

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, Russian Federation, 357502

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

Ryazan, Russian Federation, 390011

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, Russian Federation, 443031

Saratov Regional Clinical Hospital & Pathology Centre

Saratov, Russian Federation, 410053

Saint-Petersburg City Clinical Oncology Dispensary

St Petersburg, Russian Federation, 197022

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, Russian Federation, 355045

Tula Regional Oncology Dispensary

Tula, Russian Federation, 300053

GUZ Vladimir Regional Clinical Oncological Dispensary

Vladimir, Russian Federation, 600009

Slovakia

Vychodoslovensky onkologicky ustav

Kosice, Slovakia, 04001

Nzz - Oncology Outpatient Clinic

Poprad, Slovakia, 05801

South Africa

National Hospital; Oncotherapy Dept

Bloemfontein, South Africa, 9301

Cancercare

Cape Town, South Africa, 7506

Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept

Cape Town, South Africa, 7506

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

Parktown, Johannesburg, South Africa, 2193

Pretoria-East Hospital; 1 Sanwood Park

Pretoria, South Africa, 0081

Rondebosch Oncology Centre

Rondebosch, South Africa, 7700

Sandton Oncology Centre

Sandton, South Africa, 2196

Spain

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

Santiago de Compostela, LA Coruña, Spain, 15706

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

Reus, Tarragona, Spain, 43204

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Spain, 28007

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Spain, 46010

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, Spain, 50009

Sweden

Skånes University Hospital, Skånes Department of Onclology

Lund, Sweden, 22185

Akademiska sjukhuset, Onkologkliniken

Uppsala, Sweden, 75185

Taiwan

Changhua Christian Hospital; Dept of Surgery

Changhua, Taiwan, 500

Taipei Veterans General Hospital

Taipei City, Taiwan, 112

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

Taipei, Taiwan, 112

Chang Gung Medical Foundation-Taipei

Taoyuan, Taiwan, 333

Thailand

Chulalongkorn Hospital; Medical Oncology

Bangkok, Thailand, 10330

National Cancer Inst.

Bangkok, Thailand, 10400

Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

Bangkok, Thailand, 10400

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

Bangkok, Thailand, 10700

Prince of Songkla Uni ; Unit of Medical Oncology

Songkhla, Thailand, 90110

Turkey

Akdeniz University Medical Faculty; Medical Oncology Department

Antalya, Turkey, 07070

Istanbul Uni of Medicine Faculty; Oncology Dept

Istanbul, Turkey, 34390

Dokuz Eylul Uni Medical Faculty; Oncology Dept

Izmir, Turkey, 35340

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

Sıhhiye, Ankara, Turkey, 06100

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00950300
• Other Study ID Numbers: BO22227; 2008-007326-19 ( EudraCT Number )
• First Posted: July 31, 2009
• Results First Posted: January 23, 2017
• Last Update Posted: January 23, 2018
• Last Verified: December 2017

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Cyclophosphamide; Docetaxel; Fluorouracil; Trastuzumab; Epirubicin; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antimetabolites; Antimetabolites, Antineoplastic; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors