Clinical trial NCT00950300: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-07-31
Enrollment: 596
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
measure: Percentage of Participants With Pathological Complete Response (pCR)
timeFrame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
Secondary outcomes:
measure: Observed Ctrough of Trastuzumab After Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
measure: Predicted Ctrough of Trastuzumab Prior to Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
measure: Predicted Ctrough of Trastuzumab After Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
measure: Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
measure: Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery
timeFrame: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
measure: Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
timeFrame: 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)
measure: Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
timeFrame: 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)
measure: Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
timeFrame: 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)
measure: Cmax of Trastuzumab After Surgery
timeFrame: 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)
measure: Tmax of Trastuzumab After Surgery
timeFrame: 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)
measure: AUC21d of Trastuzumab After Surgery
timeFrame: 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)
measure: Percentage of Participants With Total Pathological Complete Response (tpCR)
timeFrame: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
measure: 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
timeFrame: 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)
measure: Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline
timeFrame: 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)
measure: Percentage of Participants Who Experienced a Protocol-Defined Event
timeFrame: 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)
measure: Event-Free Survival (EFS)
timeFrame: 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)
measure: Percentage of Participants Who Died
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab
timeFrame: 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
measure: Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)
timeFrame: 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
Other outcomes:
Locations:
city: Tucuman
country: Argentina
facility: Centro Medico San Roque; Oncology Dept
city: Tucuman
country: Argentina
facility: Caipo; Oncology
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: BA
city: Curitiba
country: Brazil
facility: Hospital das Clinicas - UFPR; Quimioterapia
state: PR
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Câncer
state: RN
city: Itajai
country: Brazil
facility: Clinica de Neoplasias Litoral
state: SC
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Perola Byington
state: SP
city: Sorocaba
country: Brazil
facility: Instituto de Oncologia de Sorocaba - CEPOS
state: SP
city: Montreal
country: Canada
facility: Hopital Maisonneuve- Rosemont; Oncology
state: Quebec
city: Quebec
country: Canada
facility: CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Bogota
country: Colombia
facility: Grupo Salud Coop
city: Pereira
country: Colombia
facility: Oncólogos de Occidente
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc; Onkologicka klinika
city: Pardubice
country: Czechia
facility: Krajska Nemocnice Pardubice Neurologicka Klinika
city: Praha
country: Czechia
facility: Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni
city: Praha
country: Czechia
facility: Lekarske Fakulty Univerzity Karlovy Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation; Oncology Centre
city: Tartu
country: Estonia
facility: Tartu University Hospital; Clinic of Hematology and Oncology
city: Besancon
country: France
facility: HOPITAL JEAN MINJOZ; Oncologie
city: Grenoble
country: France
facility: Institut Daniel Hollard; Chimiotherapie Ambulatoire
city: La Tronche
country: France
facility: Hopital Albert Michallon; Oncologie
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Paris
country: France
facility: Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
city: Reims
country: France
facility: Institut Jean Godinot; Hopital De Jour
city: St Cloud
country: France
facility: Centre Rene Huguenin; Medecine B
city: Berlin
country: Germany
facility: CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie
city: Berlin
country: Germany
facility: Praxis Dr. Schoenegg
city: Bonn
country: Germany
facility: Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie
city: Dortmund
country: Germany
facility: St. Johannes Hospital
city: Hannover
country: Germany
facility: Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
city: Leipzig
country: Germany
facility: Sankt Elisabeth Krankenhaus; Gynaekology
city: Lemgo
country: Germany
facility: Klinik Lippe Lemgo; Frauenklinik
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe
city: Rodewisch
country: Germany
facility: Klinik Obergöltzsch; Abt. Gynäkologie
city: Tübingen
country: Germany
facility: Universitätsklinik Tübingen; Frauenklinik
city: Guatemala
country: Guatemala
facility: Centro Oncologico S.A.
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Surgery
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Onkologiai Központ
city: Gyor
country: Hungary
facility: Hospital of Aladar Petz; Dept of Oncoradiology
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Petach Tikva
country: Israel
facility: Rabin Medical Center; Oncology Dept
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
state: Campania
city: Cremona
country: Italy
facility: ASST DI CREMONA; Dip. Medicina - S.C. Oncologia
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
state: Lombardia
city: Incheon
country: Korea, Republic of
facility: Gachon Medical School Gil Medical Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre; Division of Hematology/Oncology
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital; Oncology Haemotology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology
city: Obregon
country: Mexico
facility: Hospital Privado San Jose; Oncologia
city: Toluca
country: Mexico
facility: Centro Oncológico Estatal; ISSSEMYM Oncología
city: Panama
country: Panama
facility: Centro Oncologico America
city: Arequipa
country: Peru
facility: Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins; Oncologia
city: Lima
country: Peru
facility: Oncosalud Sac; Oncología
city: Piura
country: Peru
facility: Unidad de Investigacion Oncologia Clinica - Piura; Unidad de Oncología Clínica
city: San Isidro
country: Peru
facility: Clinica Ricardo Palma
city: Elblag
country: Poland
facility: Wojewodzki Szpital Zespolony; Oddział Onkologii
city: Lublin
country: Poland
facility: COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
city: Olsztyn
country: Poland
facility: Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: St Petersburg
country: Russian Federation
facility: FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
state: Leningrad
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center; Combined Treatment
city: Moscow
country: Russian Federation
facility: Moscow city oncology hospital #62 of Moscow Healthcare Department
city: Pyatigorsk
country: Russian Federation
facility: State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
city: Ryazan
country: Russian Federation
facility: SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
city: Samara
country: Russian Federation
facility: SBI of Healthcare Samara Regional Clinical Oncology Dispensary
city: Saratov
country: Russian Federation
facility: Saratov Regional Clinical Hospital & Pathology Centre
city: St Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary
city: Stavropol
country: Russian Federation
facility: SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary
city: Tula
country: Russian Federation
facility: Tula Regional Oncology Dispensary
city: Vladimir
country: Russian Federation
facility: GUZ Vladimir Regional Clinical Oncological Dispensary
city: Kosice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav
city: Poprad
country: Slovakia
facility: Nzz - Oncology Outpatient Clinic
city: Bloemfontein
country: South Africa
facility: National Hospital; Oncotherapy Dept
city: Cape Town
country: South Africa
facility: Cancercare
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept
city: Parktown, Johannesburg
country: South Africa
facility: Wits Donald Gordon Clinical Trial Centre; Medical Oncology
city: Pretoria
country: South Africa
facility: Pretoria-East Hospital; 1 Sanwood Park
city: Rondebosch
country: South Africa
facility: Rondebosch Oncology Centre
city: Sandton
country: South Africa
facility: Sandton Oncology Centre
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus; Servicio de Oncologia
state: Tarragona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Onkologkliniken
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital; Dept of Surgery
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Taipei
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital; Medical Oncology
city: Bangkok
country: Thailand
facility: National Cancer Inst.
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
city: Songkhla
country: Thailand
facility: Prince of Songkla Uni ; Unit of Medical Oncology
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty; Medical Oncology Department
city: Istanbul
country: Turkey
facility: Istanbul Uni of Medicine Faculty; Oncology Dept
city: Izmir
country: Turkey
facility: Dokuz Eylul Uni Medical Faculty; Oncology Dept
city: Sıhhiye, Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.