Clinical trial NCT01940497: A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
Official title: National Phase IIIb Prospective Two-Cohort Non-Randomized, Multi-centre, Open Label Study to Assess the Safety of Subcutaneous Trastuzumab and Molecular Biomarkers in Patients With Early and Locally Advanced HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-09-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This non-randomized, multicenter, open-label study will assess the safety and efficacy of subcutaneously administered trastuzumab in participants with early and locally advanced HER2-positive breast cancer in two sequential cohorts. First 120 participants will be treated with subcutaneous (SC) trastuzumab 600 milligrams (mg) vial (Cohort A) and the subsequent 120 participants will be treated with SC trastuzumab prefilled single use injection device (SID) (Cohort B). Participants from each cohort will receive neoadjuvant or adjuvant chemotherapy consisting of doxorubicin every 3 weeks (q3w) (1 cycle) for 4 cycles followed by paclitaxel weekly or docetaxel every 3 weeks (q3w) in combination with SC trastuzumab (600 mg) q3w for 4 cycles and a further 14 cycles of SC trastuzumab (600 mg) q3w alone. All participants will be followed up for 24 months after the last participant has received the last dose of study treatment, or earlier in case of withdrawal from the study, loss to follow-up or death.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast. Stage of disease: T1-4 (T describes size of tumour from 1 to 4), N0-3 (N describes nearby lymph nodes), M0 (M describes distant metastasis)
* HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Left ventricular ejection fraction (LVEF) of greater than or equal to (\>=) 55 percent (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC
* Intact skin at site of SC injection on the thigh

Exclusion Criteria:

* History of other malignancy, except for participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies, other than breast cancer, who have been disease-free for at least 5 years
* Severe dyspnea at rest or requiring supplementary oxygen therapy
* Concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension
* Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Pregnant or lactating women
* Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
* Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin including hyaluronidase, or the adhesive of the SC device (for Cohort B), or a history of severe allergic or immunological reactions, for example, difficulty to control asthma
* Inadequate bone marrow, hepatic or renal function
* Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with adjuvant trastuzumab SC)
* Pre-existing motor or sensory neuropathy of Grade greater than (\>) 1
* Synchronous bilateral invasive breast cancer

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year)
Secondary outcomes:
measure: Actual Dose of Trastuzumab Administered
timeFrame: Day 1 up last dose of trastuzumab (up to approximately 1 year)
measure: Duration of Treatment With Trastuzumab
timeFrame: Day 1 up last dose of trastuzumab (up to approximately 1 year)
measure: Percentage of Participants Who Received Concomitant Medications
timeFrame: Screening (Day -28 to -1) up to 2.5 years
measure: Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography
timeFrame: Day 1 up to 24 weeks
measure: Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography
timeFrame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])
measure: Disease-Free Survival (DFS) Using Mammography
timeFrame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])
measure: Percentage of Participants Who Died
timeFrame: Day 1 up to death due to any cause (up to approximately 4.5 years)
measure: Overall Survival (OS)
timeFrame: Day 1 up to death due to any cause (up to approximately 4.5 years)
measure: Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ)
timeFrame: After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year)
measure: Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ)
timeFrame: After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year)
Other outcomes:
Locations:
city: L'aquila
country: Italy
facility: Asl 4 - Osp. San Salvatore; Oncologia Medica
state: Abruzzo
city: Potenza
country: Italy
facility: Ospedale San Carlo; Day Hospital Oncologia Medica
state: Basilicata
city: Catanzaro
country: Italy
facility: Campus Universitario S.Venuta; Centro Oncologico T.Campanella
state: Calabria
city: Reggio Calabria
country: Italy
facility: Az. Osp. ; Divisione Oncologia Medica
state: Calabria
city: Avellino
country: Italy
facility: Azienda Ospedaliera S.G. Moscati; Division of Medical Oncology
state: Campania
city: Frattamaggiore
country: Italy
facility: Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia
state: Campania
city: Napoli
country: Italy
facility: Seconda Università di Napoli;Day Hospital Clinica Oncologia Medica
state: Campania
city: Bologna
country: Italy
facility: Ospedale Bellaria; U.O. Oncologia Medica
state: Emilia-Romagna
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
state: Emilia-Romagna
city: Carpi
country: Italy
facility: Ospedale Ramazzini ; Day Hospital Oncologico
state: Emilia-Romagna
city: Guastalla
country: Italy
facility: Ospedale Civile; Day Hospital Oncologico
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova; Oncologia
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
state: Friuli-Venezia Giulia
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Policlinico A. Gemelli-Complesso Integrato Columbus-Radioterapia
state: Lazio
city: Roma
country: Italy
facility: Uni Cattolica Policlinico Gemelli; Oncologia Medica Ist. Medicina Interna
state: Lazio
city: Roma
country: Italy
facility: Ospedale S.G.Calibita Fatebenefratelli; Unità Operativa Oncologia
state: Lazio
city: Roma
country: Italy
facility: Villa San Pietro Fatebenefatelli; Divisione Oncologia
state: Lazio
city: Genova
country: Italy
facility: Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical
state: Liguria
city: Genova
country: Italy
facility: IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
state: Liguria
city: La Spezia
country: Italy
facility: Ospedale Civile S. Andrea; Day Hospital Oncologia
state: Liguria
city: Brescia
country: Italy
facility: Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina
state: Lombardia
city: Brescia
country: Italy
facility: Casa Di Cura Poliambulanza; Unita Operativa Di Oncologia Medica
state: Lombardia
city: Como
country: Italy
facility: Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
state: Lombardia
city: Lecco
country: Italy
facility: ASST DI LECCO; Oncologia Medica
state: Lombardia
city: Mantova
country: Italy
facility: Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele;Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica
state: Lombardia
city: Saronno
country: Italy
facility: Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica
state: Lombardia
city: Treviglio
country: Italy
facility: ASST DI BERGAMO OVEST; Unità Operativa di Oncologia Medica
state: Lombardia
city: Varese
country: Italy
facility: Ospedale Di Circolo E Fondazione Macchi; Oncologia Medica
state: Lombardia
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi Ancona;S.O.D. MED.Interna-Clinica Oncologica
state: Marche
city: Macerata
country: Italy
facility: Ospedale Di Macerata; Oncologia
state: Marche
city: Pesaro
country: Italy
facility: Ospedale San Salvatore Muraglia;Divisone Oncologia
state: Marche
city: Asti
country: Italy
facility: Azienda Sanitaria Locale Di Asti-P.O. Cardinal Massaia;Oncologia
state: Piemonte
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
state: Piemonte
city: Cuneo
country: Italy
facility: Azienda Sanitaria Ospedaliera s. Croce e Carle; Oncologia Medica
state: Piemonte
city: Ponderano (BI)
country: Italy
facility: Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica
state: Piemonte
city: Torino
country: Italy
facility: Ospedale Mauriziano Umberto I; Divisione Onco-Ematologia
state: Piemonte
city: Catania
country: Italy
facility: Centro Catanese Di Oncologia; Oncologia Medica
state: Sicilia
city: Arezzo
country: Italy
facility: Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
state: Toscana
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
state: Toscana
city: Grosseto
country: Italy
facility: Ospedale della Misericordia; Hospice Terapia del Dolore
state: Toscana
city: Lido Di Camaiore
country: Italy
facility: Ospedale Nuovo Della Versilia; Divisione Di Oncologia Medica
state: Toscana
city: Livorno
country: Italy
facility: Ospedale Civile; Unita Operativa Di Oncologia Medica
state: Toscana
city: Poggibonsi
country: Italy
facility: Azienda Usl 7; Dept. Oncologico
state: Toscana
city: Sant'Andrea Delle Fratte (PG)
country: Italy
facility: Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
state: Umbria
city: Castelfranco Veneto
country: Italy
facility: Presidio Ospedaliero - Usl 13; Servizio Di Oncologia
state: Veneto
city: Mestre
country: Italy
facility: AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica
state: Veneto
city: Mirano
country: Italy
facility: Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica
state: Veneto
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria; U.O. Di Oncologia
state: Veneto
city: Treviso
country: Italy
facility: Ospedale Cà Foncello - Divisione di Oncologia Medica
state: Veneto
city: Vicenza
country: Italy
facility: Ospedale Di Vicenza; Nefrologia, Oncologia Medica
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zambetti M, Montemurro F, Morandi P, Zamagni C, Brandes AA, Bisagni G, Cagossi K, Bengala C, Gori S, Iannacone C, Stell A, Gianni L. Safety profile of subcutaneous trastuzumab for the treatment of patients with HER2-positive early or locally advanced breast cancer: primary analysis of the SCHEARLY study. Eur J Cancer. 2018 Dec;105:61-70. doi: 10.1016/j.ejca.2018.09.034. Epub 2018 Nov 3.