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

Breast Cancer Clinical Trial

— SCHEARLY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01940497
• Other study ID #: ML28879
• Secondary ID: 2013-001161-16
• Status: Completed
• Phase: Phase 3
• Start date: November 15, 2013
• Est. completion date: March 27, 2018

Study information

• Verified date: October 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: March 27, 2018
• Est. primary completion date: April 5, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Doxorubicin
Participants will receive doxorubicin in doses according to the locally-approved regimen q3w (1 cycle), for 4 cycles prior to initiation of trastuzumab treatment.
• Docetaxel
Participants will receive docetaxel in doses according to the locally-approved regimen q3w for 12 weeks, in combination with trastuzumab.
• Paclitaxel
Participants will receive paclitaxel in doses according to the locally-approved regimen weekly for 12 weeks, in combination with trastuzumab.
• Trastuzumab
Participants will receive trastuzumab 600 mg SC (vial or SID) q3w for 18 cycles.

Locations

Country	Name	City	State
Italy	A.O.U. Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi Ancona;S.O.D. MED.Interna-Clinica Oncologica	Ancona	Marche
Italy	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana
Italy	Azienda Sanitaria Locale Di Asti-P.O. Cardinal Massaia;Oncologia	Asti	Piemonte
Italy	Azienda Ospedaliera S.G. Moscati; Division of Medical Oncology	Avellino	Campania
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	Ospedale Bellaria; U.O. Oncologia Medica	Bologna	Emilia-Romagna
Italy	Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina	Brescia	Lombardia
Italy	Casa Di Cura Poliambulanza; Unita Operativa Di Oncologia Medica	Brescia	Lombardia
Italy	Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico	Candiolo	Piemonte
Italy	Ospedale Ramazzini ; Day Hospital Oncologico	Carpi	Emilia-Romagna
Italy	Presidio Ospedaliero - Usl 13; Servizio Di Oncologia	Castelfranco Veneto	Veneto
Italy	Centro Catanese Di Oncologia; Oncologia Medica	Catania	Sicilia
Italy	Campus Universitario S.Venuta; Centro Oncologico T.Campanella	Catanzaro	Calabria
Italy	Ospedale Valduce;U.O.S. Oncologia Ed Ematologia	Como	Lombardia
Italy	Azienda Sanitaria Ospedaliera s. Croce e Carle; Oncologia Medica	Cuneo	Piemonte
Italy	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana
Italy	Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia	Frattamaggiore	Campania
Italy	Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical	Genova	Liguria
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Ospedale della Misericordia; Hospice Terapia del Dolore	Grosseto	Toscana
Italy	Ospedale Civile; Day Hospital Oncologico	Guastalla	Emilia-Romagna
Italy	Asl 4 - Osp. San Salvatore; Oncologia Medica	L'aquila	Abruzzo
Italy	Ospedale Civile S. Andrea; Day Hospital Oncologia	La Spezia	Liguria
Italy	ASST DI LECCO; Oncologia Medica	Lecco	Lombardia
Italy	Ospedale Nuovo Della Versilia; Divisione Di Oncologia Medica	Lido Di Camaiore	Toscana
Italy	Ospedale Civile; Unita Operativa Di Oncologia Medica	Livorno	Toscana
Italy	Ospedale Di Macerata; Oncologia	Macerata	Marche
Italy	Az. Osp. Carlo Poma; Divisione Di Oncologia Medica	Mantova	Lombardia
Italy	AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica	Mestre	Veneto
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica	Mirano	Veneto
Italy	Seconda Università di Napoli;Day Hospital Clinica Oncologia Medica	Napoli	Campania
Italy	Ospedale Sacro Cuore Don Calabria; U.O. Di Oncologia	Negrar	Veneto
Italy	Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica	Pavia	Lombardia
Italy	Ospedale San Salvatore Muraglia;Divisone Oncologia	Pesaro	Marche
Italy	Azienda Usl 7; Dept. Oncologico	Poggibonsi	Toscana
Italy	Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica	Ponderano (BI)	Piemonte
Italy	Ospedale San Carlo; Day Hospital Oncologia Medica	Potenza	Basilicata
Italy	Az. Osp. ; Divisione Oncologia Medica	Reggio Calabria	Calabria
Italy	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna
Italy	Ospedale S.G.Calibita Fatebenefratelli; Unità Operativa Oncologia	Roma	Lazio
Italy	Policlinico A. Gemelli-Complesso Integrato Columbus-Radioterapia	Roma	Lazio
Italy	Uni Cattolica Policlinico Gemelli; Oncologia Medica Ist. Medicina Interna	Roma	Lazio
Italy	Villa San Pietro Fatebenefatelli; Divisione Oncologia	Roma	Lazio
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Sant'Andrea Delle Fratte (PG)	Umbria
Italy	Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica	Saronno	Lombardia
Italy	Ospedale Mauriziano Umberto I; Divisione Onco-Ematologia	Torino	Piemonte
Italy	ASST DI BERGAMO OVEST; Unità Operativa di Oncologia Medica	Treviglio	Lombardia
Italy	Ospedale Cà Foncello - Divisione di Oncologia Medica	Treviso	Veneto
Italy	Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia	Udine	Friuli-Venezia Giulia
Italy	Ospedale Di Circolo E Fondazione Macchi; Oncologia Medica	Varese	Lombardia
Italy	Ospedale Di Vicenza; Nefrologia, Oncologia Medica	Vicenza	Veneto

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the AEs occurring from starting on the day of or after first administration of trastuzumab and within 28 days after last dose of trastuzumab. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year)
Secondary	Actual Dose of Trastuzumab Administered	Actual dose (mg) administered = (sum over all cycles of actual dose received [mg] divided by number of cycles). Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	Day 1 up last dose of trastuzumab (up to approximately 1 year)
Secondary	Duration of Treatment With Trastuzumab	Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	Day 1 up last dose of trastuzumab (up to approximately 1 year)
Secondary	Percentage of Participants Who Received Concomitant Medications		Screening (Day -28 to -1) up to 2.5 years
Secondary	Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography	In the neoadjuvant setting, the activity of two sequential drug regimens, doxorubicin-containing chemotherapy followed by paclitaxel or docetaxel chemotherapy in combination with trastuzumab, was assessed as the percentage of participants with pCR in breast and nodes using mammography. pCR was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after preoperative treatment. Data for this outcome measure were analyzed and reported only for neoadjuvant groups within each treatment arm.	Day 1 up to 24 weeks
Secondary	Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography	A participant was considered as disease free if the participant was free from local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Percentage of participants with event at the cut off date were reported. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	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])
Secondary	Disease-Free Survival (DFS) Using Mammography	DFS was defined as the time from the first treatment to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Kaplan-Meier estimates were used for analysis. Participants who were disease-free were censored at the data cut off date. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	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])
Secondary	Percentage of Participants Who Died	Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	Day 1 up to death due to any cause (up to approximately 4.5 years)
Secondary	Overall Survival (OS)	Overall survival was defined as the time from the first treatment to death from any cause. Kaplan-Meier estimates were used for analysis. Participants who did not die were censored on the date they were last known to be alive. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.	Day 1 up to death due to any cause (up to approximately 4.5 years)
Secondary	Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ)	Participants were asked the following 5 questions: (1) "Following the first injection given by the physician/nurse and training on how to use the SID, I felt comfortable injecting the study drug by myself"; (2) "The SID was convenient and easy to use"; (3) "I am confident giving myself an injection in the thigh with the SID"; (4) "Taking all things into account, I find self-administration using the SID satisfactory"; (5) "If given the opportunity, I would choose to continue self-injecting the study drug using the SID at home". Response to each question was recorded as either of the following options: "Unknown", "Strongly Disagree", "Disagree", "Unsure", "Agree", "Strongly Agree". Percentage of participants who provided responses to above questions was reported. Data for this outcome measure were analyzed and reported only for Trastuzumab (SID) arm.	After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year)
Secondary	Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ)	Percentage of HCPs providing responses to various questions related to overall ease of study drug administration was reported in different categories, where categories indicate all possible responses to such questions.	After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year)