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

NCT01940497 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ML288792013-001161-16
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 54

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Actual Dose of Trastuzumab Administered

  Day 1 up last dose of trastuzumab (up to approximately 1 year)

• Duration of Treatment With Trastuzumab

  Day 1 up last dose of trastuzumab (up to approximately 1 year)

• Percentage of Participants Who Received Concomitant Medications

  Screening (Day -28 to -1) up to 2.5 years

• Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography

  Day 1 up to 24 weeks

• 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])

Study Arms (2)

Trastuzumab (Vial)

EXPERIMENTAL

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).

Drug: Doxorubicin; Drug: Docetaxel; Drug: Paclitaxel; Drug: Trastuzumab

Trastuzumab (SID)

EXPERIMENTAL

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).

Drug: Doxorubicin; Drug: Docetaxel; Drug: Paclitaxel; Drug: Trastuzumab

Interventions

Doxorubicin DRUG

Participants will receive doxorubicin in doses according to the locally-approved regimen q3w (1 cycle), for 4 cycles prior to initiation of trastuzumab treatment.

Trastuzumab (SID); Trastuzumab (Vial)

Docetaxel DRUG

Participants will receive docetaxel in doses according to the locally-approved regimen q3w for 12 weeks, in combination with trastuzumab.

Trastuzumab (SID); Trastuzumab (Vial)

Paclitaxel DRUG

Participants will receive paclitaxel in doses according to the locally-approved regimen weekly for 12 weeks, in combination with trastuzumab.

Trastuzumab (SID); Trastuzumab (Vial)

Trastuzumab DRUG

Participants will receive trastuzumab 600 mg SC (vial or SID) q3w for 18 cycles.

Also known as: Herceptin

Trastuzumab (SID); Trastuzumab (Vial)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (54)

Asl 4 - Osp. San Salvatore; Oncologia Medica

L’Aquila, Abruzzo, 67010, Italy

Location

Ospedale San Carlo; Day Hospital Oncologia Medica

Potenza, Basilicate, 85100, Italy

Location

Campus Universitario S.Venuta; Centro Oncologico T.Campanella

Catanzaro, Calabria, 88100, Italy

Location

Az. Osp. ; Divisione Oncologia Medica

Reggio Calabria, Calabria, 89100, Italy

Location

Azienda Ospedaliera S.G. Moscati; Division of Medical Oncology

Avellino, Campania, 83100, Italy

Location

Presidio Ospedaliero S. Giovanni Di Dio; U.O. Di Oncologia

Frattamaggiore, Campania, 80027, Italy

Location

Seconda Università di Napoli;Day Hospital Clinica Oncologia Medica

Napoli, Campania, 80131, Italy

Location

Ospedale Bellaria; U.O. Oncologia Medica

Bologna, Emilia-Romagna, 40133, Italy

Location

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale Ramazzini ; Day Hospital Oncologico

Carpi, Emilia-Romagna, 41012, Italy

Location

Ospedale Civile; Day Hospital Oncologico

Guastalla, Emilia-Romagna, 42016, Italy

Location

Arcispedale Santa Maria Nuova; Oncologia

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia

Udine, Friuli Venezia Giulia, 33100, Italy

Location

Policlinico A. Gemelli-Complesso Integrato Columbus-Radioterapia

Rome, Lazio, 00168, Italy

Location

Uni Cattolica Policlinico Gemelli; Oncologia Medica Ist. Medicina Interna

Rome, Lazio, 00168, Italy

Location

Ospedale S.G.Calibita Fatebenefratelli; Unità Operativa Oncologia

Rome, Lazio, 00186, Italy

Location

Villa San Pietro Fatebenefatelli; Divisione Oncologia

Rome, Lazio, 00189, Italy

Location

Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical

Genoa, Liguria, 16132, Italy

Location

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genoa, Liguria, 16132, Italy

Location

Ospedale Civile S. Andrea; Day Hospital Oncologia

La Spezia, Liguria, 19125, Italy

Location

Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina

Brescia, Lombardy, 25123, Italy

Location

Casa Di Cura Poliambulanza; Unita Operativa Di Oncologia Medica

Brescia, Lombardy, 25124, Italy

Location

Ospedale Valduce;U.O.S. Oncologia Ed Ematologia

Como, Lombardy, 22100, Italy

Location

ASST DI LECCO; Oncologia Medica

Lecco, Lombardy, 23900, Italy

Location

Az. Osp. Carlo Poma; Divisione Di Oncologia Medica

Mantova, Lombardy, 46100, Italy

Location

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, 20132, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica

Pavia, Lombardy, 27100, Italy

Location

Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica

Saronno, Lombardy, 21047, Italy

Location

ASST DI BERGAMO OVEST; Unità Operativa di Oncologia Medica

Treviglio, Lombardy, 24047, Italy

Location

Ospedale Di Circolo E Fondazione Macchi; Oncologia Medica

Varese, Lombardy, 21100, Italy

Location

Azienda Sanitaria Locale Di Asti-P.O. Cardinal Massaia;Oncologia

Asti, Piedmont, 14100, Italy

Location

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico

Candiolo, Piedmont, 10060, Italy

Location

Azienda Sanitaria Ospedaliera s. Croce e Carle; Oncologia Medica

Cuneo, Piedmont, 12100, Italy

Location

Ospedale Degli Infermi Di Biella; Reparto Oncologia Medica

Ponderano (BI), Piedmont, 13875, Italy

Location

Ospedale Mauriziano Umberto I; Divisione Onco-Ematologia

Turin, Piedmont, 10128, Italy

Location

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicily, 95126, Italy

Location

A.O.U. Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi Ancona;S.O.D. MED.Interna-Clinica Oncologica

Ancona, The Marches, 60121, Italy

Location

Ospedale Di Macerata; Oncologia

Macerata, The Marches, 62100, Italy

Location

Ospedale San Salvatore Muraglia;Divisone Oncologia

Pesaro, The Marches, 61122, Italy

Location

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia

Arezzo, Tuscany, 52100, Italy

Location

Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1

Florence, Tuscany, 50139, Italy

Location

Ospedale della Misericordia; Hospice Terapia del Dolore

Grosseto, Tuscany, 58100, Italy

Location

Ospedale Nuovo Della Versilia; Divisione Di Oncologia Medica

Lido di Camaiore, Tuscany, 55043, Italy

Location

Ospedale Civile; Unita Operativa Di Oncologia Medica

Livorno, Tuscany, 57100, Italy

Location

Azienda Usl 7; Dept. Oncologico

Poggibonsi, Tuscany, 53036, Italy

Location

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Sant'Andrea Delle Fratte (PG), Umbria, 06132, Italy

Location

Presidio Ospedaliero - Usl 13; Servizio Di Oncologia

Castelfranco Veneto, Veneto, 31033, Italy

Location

AZ. Usll12 Veneziana-Ospedale Dell'angelo;Oncologia Medica

Mestre, Veneto, 30174, Italy

Location

Ospedale Calvi di Noale; U.O. Complessa di Oncologia ed Ematologia Oncologica

Mirano, Veneto, 30035, Italy

Location

Ospedale Sacro Cuore Don Calabria; U.O. Di Oncologia

Negrar, Veneto, 37024, Italy

Location

Ospedale Cà Foncello - Divisione di Oncologia Medica

Treviso, Veneto, 31100, Italy

Location

Ospedale Di Vicenza; Nefrologia, Oncologia Medica

Vicenza, Veneto, 36100, Italy

Location

Related Publications (1)

• 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.

  PMID: 30396014 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Docetaxel; Paclitaxel; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2013
• First Posted: September 12, 2013
• Study Start: November 15, 2013
• Primary Completion: April 5, 2016
• Study Completion: March 27, 2018
• Last Updated: November 3, 2020
• Results First Posted: July 2, 2017

Record last verified: 2020-10

Locations

IT (54)