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
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01940497
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 240
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Trastuzumab (Vial) Docetaxel Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (Vial) Paclitaxel Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (Vial) Doxorubicin Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (Vial) Trastuzumab Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (SID) Doxorubicin Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (SID) Docetaxel Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (SID) Paclitaxel Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone). Trastuzumab (SID) Trastuzumab Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year) 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography Day 1 up to 24 weeks 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.
Actual Dose of Trastuzumab Administered Day 1 up last dose of trastuzumab (up to approximately 1 year) 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.
Duration of Treatment With Trastuzumab Day 1 up last dose of trastuzumab (up to approximately 1 year) Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.
Percentage of Participants Who Received Concomitant Medications Screening (Day -28 to -1) up to 2.5 years Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography 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]) 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.
Disease-Free Survival (DFS) Using Mammography 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]) 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.
Percentage of Participants Who Died Day 1 up to death due to any cause (up to approximately 4.5 years) Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.
Overall Survival (OS) Day 1 up to death due to any cause (up to approximately 4.5 years) 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.
Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ) After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year) 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.
Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ) After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 daysÍž maximum up to 1 year) 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.
Trial Locations
- Locations (54)
Ospedale S.G.Calibita Fatebenefratelli; UnitĂ Operativa Oncologia
đŽđšRoma, Lazio, Italy
Campus Universitario S.Venuta; Centro Oncologico T.Campanella
đŽđšCatanzaro, Calabria, Italy
Ospedale San Carlo; Day Hospital Oncologia Medica
đŽđšPotenza, Basilicata, Italy
Arcispedale Santa Maria Nuova; Oncologia
đŽđšReggio Emilia, Emilia-Romagna, Italy
Villa San Pietro Fatebenefatelli; Divisione Oncologia
đŽđšRoma, Lazio, Italy
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; UnitĂ Operativa Oncologia Medica
đŽđšBologna, Emilia-Romagna, Italy
Ospedale Ramazzini ; Day Hospital Oncologico
đŽđšCarpi, Emilia-Romagna, Italy
Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
đŽđšUdine, Friuli-Venezia Giulia, Italy
Ospedale Bellaria; U.O. Oncologia Medica
đŽđšBologna, Emilia-Romagna, Italy
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
đŽđšGenova, Liguria, Italy
Ospedale Civile S. Andrea; Day Hospital Oncologia
đŽđšLa Spezia, Liguria, Italy
Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
đŽđšSant'Andrea Delle Fratte (PG), Umbria, Italy
Centro Catanese Di Oncologia; Oncologia Medica
đŽđšCatania, Sicilia, Italy
Asl 4 - Osp. San Salvatore; Oncologia Medica
đŽđšL'aquila, Abruzzo, Italy
Az. Osp. ; Divisione Oncologia Medica
đŽđšReggio Calabria, Calabria, Italy
Seconda UniversitĂ di Napoli;Day Hospital Clinica Oncologia Medica
đŽđšNapoli, Campania, Italy
Azienda Ospedaliera S.G. Moscati; Division of Medical Oncology
đŽđšAvellino, Campania, Italy
Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia
đŽđšFrattamaggiore, Campania, Italy
Policlinico A. Gemelli-Complesso Integrato Columbus-Radioterapia
đŽđšRoma, Lazio, Italy
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
đŽđšAviano, Friuli-Venezia Giulia, Italy
Uni Cattolica Policlinico Gemelli; Oncologia Medica Ist. Medicina Interna
đŽđšRoma, Lazio, Italy
Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical
đŽđšGenova, Liguria, Italy
Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina
đŽđšBrescia, Lombardia, Italy
Casa Di Cura Poliambulanza; Unita Operativa Di Oncologia Medica
đŽđšBrescia, Lombardia, Italy
Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
đŽđšComo, Lombardia, Italy
ASST DI LECCO; Oncologia Medica
đŽđšLecco, Lombardia, Italy
Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
đŽđšMantova, Lombardia, Italy
Irccs Ospedale San Raffaele;Oncologia Medica
đŽđšMilano, Lombardia, Italy
Istituto Europeo Di Oncologia
đŽđšMilano, Lombardia, Italy
Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica
đŽđšPavia, Lombardia, Italy
Ospedale Di Circolo E Fondazione Macchi; Oncologia Medica
đŽđšVarese, Lombardia, Italy
Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica
đŽđšSaronno, Lombardia, Italy
A.O.U. Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi Ancona;S.O.D. MED.Interna-Clinica Oncologica
đŽđšAncona, Marche, Italy
Ospedale Di Macerata; Oncologia
đŽđšMacerata, Marche, Italy
Ospedale San Salvatore Muraglia;Divisone Oncologia
đŽđšPesaro, Marche, Italy
ASST DI BERGAMO OVEST; UnitĂ Operativa di Oncologia Medica
đŽđšTreviglio, Lombardia, Italy
Azienda Sanitaria Locale Di Asti-P.O. Cardinal Massaia;Oncologia
đŽđšAsti, Piemonte, Italy
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
đŽđšCandiolo, Piemonte, Italy
Azienda Sanitaria Ospedaliera s. Croce e Carle; Oncologia Medica
đŽđšCuneo, Piemonte, Italy
Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica
đŽđšPonderano (BI), Piemonte, Italy
Ospedale Mauriziano Umberto I; Divisione Onco-Ematologia
đŽđšTorino, Piemonte, Italy
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
đŽđšArezzo, Toscana, Italy
Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
đŽđšFirenze, Toscana, Italy
Ospedale Civile; Unita Operativa Di Oncologia Medica
đŽđšLivorno, Toscana, Italy
Ospedale della Misericordia; Hospice Terapia del Dolore
đŽđšGrosseto, Toscana, Italy
Ospedale Nuovo Della Versilia; Divisione Di Oncologia Medica
đŽđšLido Di Camaiore, Toscana, Italy
Azienda Usl 7; Dept. Oncologico
đŽđšPoggibonsi, Toscana, Italy
AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica
đŽđšMestre, Veneto, Italy
Presidio Ospedaliero - Usl 13; Servizio Di Oncologia
đŽđšCastelfranco Veneto, Veneto, Italy
Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica
đŽđšMirano, Veneto, Italy
Ospedale Di Vicenza; Nefrologia, Oncologia Medica
đŽđšVicenza, Veneto, Italy
Ospedale CĂ Foncello - Divisione di Oncologia Medica
đŽđšTreviso, Veneto, Italy
Ospedale Sacro Cuore Don Calabria; U.O. Di Oncologia
đŽđšNegrar, Veneto, Italy
Ospedale Civile; Day Hospital Oncologico
đŽđšGuastalla, Emilia-Romagna, Italy