AzTrials
AzTrials

Breast CancerPhase 3NCT00950300

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

A Phase 3 study testing 5-Fluorouracil, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Hoffmann-La Roche at 106 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
5-Fluorouracil, Cyclophosphamide and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
596 participants
Where
106 sitesin 26 countries
Study dates
16 Oct 2009to 24 Jan 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

106 sites in 26 countries.

106 sites in 26 countries

Russia12 sites

  • Ivanovo Regional Oncology Dispensary

    Ivanovo, 153040

  • Blokhin Cancer Research Center; Combined Treatment

    Moscow, 115478

  • Moscow city oncology hospital #62 of Moscow Healthcare Department

    Moscow, 143423

  • State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

    Pyatigorsk, 357502

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

    Ryazan, 390011

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

    Saint Petersburg, Sankt-Peterburg, 197758

  • Saint-Petersburg City Clinical Oncology Dispensary

    Saint Petersburg, 197022

  • SBI of Healthcare Samara Regional Clinical Oncology Dispensary

    Samara, 443031

  • Saratov Regional Clinical Hospital & Pathology Centre

    Saratov, 410053

  • SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

    Stavropol, 355045

  • Tula Regional Oncology Dispensary

    Tula, 300053

  • GUZ Vladimir Regional Clinical Oncological Dispensary

    Vladimir, 600009

Other trials in Russia

Germany10 sites

  • CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

    Berlin, 10117

  • Praxis Dr. Schoenegg

    Berlin, 10719

  • Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie

    Bonn, 53113

  • St. Johannes Hospital

    Dortmund, 44137

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

    Hanover, 30177

  • Sankt Elisabeth Krankenhaus; Gynaekology

    Leipzig, 04277

  • Klinik Lippe Lemgo; Frauenklinik

    Lemgo, 32657

  • Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

    Offenbach, 63069

  • Klinik Obergöltzsch; Abt. Gynäkologie

    Rodewisch, 08228

  • Universitätsklinik Tübingen; Frauenklinik

    Tübingen, 72076

Other trials in Germany

Brazil8 sites

  • Hospital das Clinicas - UFPR; Quimioterapia

    Curitiba, Paraná, 80060-900

  • Clinica de Neoplasias Litoral

    Itajaí, Santa Catarina, 88301-220

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-080

  • Liga Norte Riograndense Contra O Câncer

    Natal, Rio Grande do Norte, 59040150

  • Hospital Sao Rafael - HSR

    Salvador, Estado de Bahia, 41253-190

  • Instituto do Cancer do Estado de Sao Paulo - ICESP

    São Paulo, São Paulo, 01246-000

  • Hospital Perola Byington

    São Paulo, São Paulo, 01317-000

  • Instituto de Oncologia de Sorocaba - CEPOS

    Sorocaba, São Paulo, 18030-245

Other trials in Brazil

France7 sites

  • HOPITAL JEAN MINJOZ; Oncologie

    Besançon, 25030

  • Institut Daniel Hollard; Chimiotherapie Ambulatoire

    Grenoble, 38000

  • Hopital Albert Michallon; Oncologie

    La Tronche, 38700

  • Centre Jean Bernard

    Le Mans, 72015

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

    Paris, 75475

  • Institut Jean Godinot; Hopital De Jour

    Reims, 51056

  • Centre Rene Huguenin; Medecine B

    Saint-Cloud, 92210

Other trials in France

South Africa7 sites

  • National Hospital; Oncotherapy Dept

    Bloemfontein, 9301

  • Cancercare

    Cape Town, 7506

  • Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept

    Cape Town, 7506

  • Wits Donald Gordon Clinical Trial Centre; Medical Oncology

    Parktown, Johannesburg, 2193

  • Pretoria-East Hospital; 1 Sanwood Park

    Pretoria, 0081

  • Rondebosch Oncology Centre

    Rondebosch, 7700

  • Sandton Oncology Centre

    Sandton, 2196

Other trials in South Africa

Peru5 sites

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

    Arequipa, 04001

  • Hospital Nacional Edgardo Rebagliati Martins; Oncologia

    Lima, 11

  • Oncosalud Sac; Oncología

    Lima, 41

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

    Piura, 20011

  • Clinica Ricardo Palma

    San Isidro, Lima 27

Other trials in Peru

Spain5 sites

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, 28007

  • Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

    Reus, Tarragona, 43204

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

    Santiago de Compostela, LA Coruña, 15706

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010

  • Hospital Universitario Miguel Servet; Servicio Oncologia

    Zaragoza, 50009

Other trials in Spain

Thailand5 sites

  • Chulalongkorn Hospital; Medical Oncology

    Bangkok, 10330

  • National Cancer Inst.

    Bangkok, 10400

  • Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

    Bangkok, 10400

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

    Bangkok, 10700

  • Prince of Songkla Uni ; Unit of Medical Oncology

    Songkhla, 90110

Other trials in Thailand

Czechia4 sites

  • Fakultni nemocnice Olomouc; Onkologicka klinika

    Olomouc, 779 00

  • Krajska Nemocnice Pardubice Neurologicka Klinika

    Pardubice, 532 03

  • Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni

    Prague, 140 59

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

    Prague, 180 81

Other trials in Czechia

Italy4 sites

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

    Cremona, Lombardy, 26100

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

    Naples, Campania, 80131

  • Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica

    Pavia, Lombardy, 27100

  • Fondazione Salvatore Maugeri

    Pavia, Lombardy, 27100

Other trials in Italy

Poland4 sites

  • Wojewodzki Szpital Zespolony; Oddział Onkologii

    Elblag, 82-300

  • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

    Lublin, 20-090

  • Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

    Olsztyn, 10-513

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

    Warsaw, 02-781

Other trials in Poland

South Korea4 sites

  • Gachon Medical School Gil Medical Center; Medical Oncology

    Incheon, 405-760

  • Samsung Medical Centre; Division of Hematology/Oncology

    Seoul, 135-710

  • Korea University Anam Hospital; Oncology Haemotology

    Seoul, 136-705

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

    Seoul, 138-736

Other trials in South Korea

Taiwan4 sites

  • Changhua Christian Hospital; Dept of Surgery

    Changhua, 500

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

    Taipei, 112

  • Taipei Veterans General Hospital

    Taipei, 112

  • Chang Gung Medical Foundation-Taipei

    Taoyuan, 333

Other trials in Taiwan

Turkey (Türkiye)4 sites

  • Akdeniz University Medical Faculty; Medical Oncology Department

    Antalya, 07070

  • Istanbul Uni of Medicine Faculty; Oncology Dept

    Istanbul, 34390

  • Dokuz Eylul Uni Medical Faculty; Oncology Dept

    Izmir, 35340

  • Hacettepe Uni Medical Faculty Hospital; Oncology Dept

    Sıhhiye, Ankara, 06100

Other trials in Turkey (Türkiye)

Colombia3 sites

  • Hospital Universitario San Ignacio

    Bogotá, 000472

  • Grupo Salud Coop

    Bogotá

  • Oncólogos de Occidente

    Pereira, 600004

Other trials in Colombia

Hungary3 sites

  • Semmelweis Egyetem Onkologiai Központ

    Budapest, 1083

  • Hospital of Aladar Petz; Dept of Oncoradiology

    Győr, 9023

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

    Szeged, 6720

Other trials in Hungary

Argentina2 sites

  • Centro Medico San Roque; Oncology Dept

    San Miguel de Tucumán, T4000IAK

  • Caipo; Oncology

    San Miguel de Tucumán, T400IAK

Other trials in Argentina

Canada2 sites

  • Hopital Maisonneuve- Rosemont; Oncology

    Montreal, Quebec, H1T 2M4

  • CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

    Québec, G1S 4L8

Other trials in Canada

Estonia2 sites

  • North Estonia Medical Centre Foundation; Oncology Centre

    Tallinn, 13419

  • Tartu University Hospital; Clinic of Hematology and Oncology

    Tartu, 50406

Other trials in Estonia

Israel2 sites

  • Hadassah Ein Karem Hospital; Oncology Dept

    Jerusalem, 9112001

  • Rabin Medical Center; Oncology Dept

    Petah Tikva, 49100

Other trials in Israel

Mexico2 sites

  • Hospital Privado San Jose; Oncologia

    Obregón, 85000

  • Centro Oncológico Estatal; ISSSEMYM Oncología

    Toluca, 50180

Other trials in Mexico

Slovakia2 sites

  • Vychodoslovensky onkologicky ustav

    Košice, 04001

  • Nzz - Oncology Outpatient Clinic

    Poprad, 05801

Other trials in Slovakia

Sweden2 sites

  • Skånes University Hospital, Skånes Department of Onclology

    Lund, 22185

  • Akademiska sjukhuset, Onkologkliniken

    Uppsala, 75185

Other trials in Sweden

Guatemala1 site

  • Centro Oncologico S.A.

    Guatemala City, 01010

Other trials in Guatemala

Hong Kong1 site

  • Queen Mary Hospital; Surgery

    Hong Kong, 852

Other trials in Hong Kong

Panama1 site

  • Centro Oncologico America

    Panama City, 0834-02723

Other trials in Panama

About this study

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)

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
Being tested
5-Fluorouracil, Cyclophosphamide, Docetaxel, Epirubicin, Herceptin IV [trastuzumab]
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-FluorouracilDrug

    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.

  • CyclophosphamideDrug

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

  • DocetaxelDrug

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

  • EpirubicinDrug

    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]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 [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.

Study groups in NCT00950300
Study groupRoleWhat they receive
Herceptin IV + ChemotherapyActive comparatorParticipants 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.
Receives: Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Herceptin IV [trastuzumab]
Herceptin SC + ChemotherapyExperimentalParticipants 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.
Receives: Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Herceptin SC [trastuzumab]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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.

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

Secondary outcomes (20)

  1. Observed Ctrough of Trastuzumab After Surgery

    Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL.

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

  2. Predicted Ctrough of Trastuzumab Prior to Surgery

    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.

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

  3. Predicted Ctrough of Trastuzumab After Surgery

    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.

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

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

    Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough >20 μg/mL was reported.

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

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

    Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough >20 μg/mL was reported.

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

  6. Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery

    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.

    Measured: 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)

  7. Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery

    PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days.

    Measured: 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)

  8. Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery

    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).

    Measured: 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)

  9. Cmax of Trastuzumab After Surgery

    PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL.

    Measured: 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)

  10. Tmax of Trastuzumab After Surgery

    PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days.

    Measured: 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)

  11. AUC21d of Trastuzumab After Surgery

    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.

    Measured: 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)

  12. Percentage of Participants With Total Pathological Complete Response (tpCR)

    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.

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

  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

    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.

    Measured: 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)

  14. Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline

    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.

    Measured: 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)

  15. Percentage of Participants Who Experienced a Protocol-Defined Event

    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.

    Measured: 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)

  16. Event-Free Survival (EFS)

    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.

    Measured: 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)

  17. Percentage of Participants Who Died

    The percentage of participants who died at any time during the study was reported.

    Measured: 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)

  18. Overall Survival (OS)

    OS was estimated by Kaplan-Meier analysis and defined as the time from randomization to death from any cause.

    Measured: 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)

  19. Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab

    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).

    Measured: 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

  20. Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)

    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).

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2009 (estimated)
  2. Study start16 Oct 2009
  3. Primary completion12 Jul 2011
  4. Study completion24 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
596 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00950300
Sponsor's protocol ID
BO22227
Other IDs
2008-007326-19, 2008
Status last verified
Dec 2017
First submitted
30 Jul 2009
Last updated
23 Jan 2018

Publications

  • 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.

    PubMed 30998824

  • 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.

    PubMed 22884505

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 5-Fluorouracil, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Hoffmann-La Roche at 106 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 106 sites in Russia, Germany, Brazil, France, South Africa and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00950300, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in