A TWO-ARM, NON-RANDOMIZED, MULTICENTER, MULTINATIONAL, OPEN-LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED-AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS ADJUVANT THERAPY IN PATIENTS WITH OPERABLE Her2-positive early breast cancer

• Register: EUCTR
• Last refreshed on: 30 November 2020
• Main ID: EUCTR2011-005328-17-IT
• Date of registration: 29/03/2012
• Prospective Registration: No
• Primary sponsor: F. HOFFMANN - LA ROCHE LTD.
• Public title: A TWO-ARM, NON-RANDOMIZED, MULTICENTER, MULTINATIONAL, OPEN-LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED-AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS ADJUVANT THERAPY IN PATIENTS WITH OPERABLE Her2-positive early breast cancer
• Scientific title: A PHASE III PROSPECTIVE, TWO-COHORT NON-RANDOMIZED, MULTI-CENTRE, MULTINATIONAL, OPEN LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED- AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS ADJUVANT THERAPY IN PATIENTS WITH OPERABLE HER2-POSITIVE EARLY BREAST CANCER [SafeHer Study] - SafHer Study
• Date of first enrolment: 21/03/2012
• Target sample size: 2500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005328-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Algeria, Argentina, Australia, Bahrain, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Dominican Republic, Ecuador, Egypt, El Salvador, European Union, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Indonesia, Ireland, Italy, Korea, Republic of, Kuwait, Lebanon, Lithuania, Malaysia, Mexico, Moldova, Republic of, Morocco, Netherlands, New Zealand, Norway, Pakistan, Panama, Peru, Philippines, Poland, Portugal, Qatar, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Trinidad and Tobago, Tunisia, Turkey, Ukraine, United Arab Emirates, United Kingdom, Venezuela, Bolivarian Republic of, Vietnam

Contacts

• Name: Ethics & Administrative Trial Unit
• Affiliation: Roche S.p.A.

• Name: Ethics & Administrative Trial Unit
• Affiliation: Roche S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent approved by the reviewing independent Ethics Committee (EC) 2. Female or male aged 18 years or above 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Histologically confirmed early invasive HER2-positive carcinoma of the breast with no evidence of residual, locally recurrent or metastatic disease and defined as clinical stage I (T1, N0, M0) to IIIC (any T, N3, M0) that is eligible for adjuvant treatment with trastuzumab Note: Patients treated without neoadjuvant or adjuvant chemotherapy, such as patients with low risk node negative tumours = 1.0 cm, elderly patients (>65 years of age) or patients with HER2-positive EBC but denying chemotherapy, will also be eligible to participate in the study, but their enrolment will be limited to approximately 10% of the total study population. 5. HER2-positive EBC, defined as IHC 3+, or FISH/CISH positive, as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay 6. Screening left ventricular ejection fraction (LVEF) = 55% as measured by echocardiography, Multi Gated Acquisition (MUGA) scan or Magnetic Resonance Imaging (MRI) per local practice 7. Agreement to use an adequate, non-hormonal means of contraception by women of childbearing potential (defined as pre-menopausal and not surgically sterilized or < 1 year after the onset of menopause) and by male participants with partners of childbearing potential only. 8. Intact skin at site of SC injection on the thigh.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion criteria:
Cancer related Criteria:1. Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent 2. History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and patients with other curatively-treated malignancies who have been disease-free for at least 5 years, are eligible. 3.Past history of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS) that has been treated with any systemic therapy OR with radiation therapy to the ipsilateral breast where invasive cancer subsequently develops. Patients who had their DCIS/LCIS treated with surgery only are allowed to enter the study. 4.Metastatic disease Haematological, Biochemical and Organ Function: 5.Inadequate bone marrow function (as indicated by any of the following): o Total white blood cell count (WBC) < 2,500 / mm3 (<2.5 x 109/L) o Absolute neutrophil count (ANC) < 1,500 / mm3 (< 1.5 x 109/L) o Platelets < 100,000 / mm3 (< 100 x 109/L) o Haemoglobin < 10 g/dL 6. Impaired hepatic function (as indicated by any of the following): o Serum total bilirubin > 1.5 x upper limit of normal (ULN) o Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) >1.25 x ULN o Alkaline phosphatase (ALP) >2.5 x ULN 7. Impaired renal function, as indicated by serum creatinine > 1.5 x ULN Other Study Drug-related Exclusion Criteria: 8. Serious cardiac illness or medical conditions including but not confined to: o History of documented heart failure or systolic dysfunction (LVEF < 50%) o High-risk uncontrolled arrhythmias such as atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular (AV) block (second degree AV-block Type 2 [Mobitz 2] or third degree AV-block) o Angina pectoris requiring anti-anginal medication o Clinically significant valvular heart disease o Evidence of transmural infarction on electrocardiogram (ECG) o Poorly controlled hypertension, or history of hypertensive crisis or hypertensive encephalopathy 9. Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness 10.Prior maximum cumulative dose of doxorubicin >360 mg/m2 or maximum cumulative dose of epirubicin >720 mg/m2 or equivalent 11.Known hypersensitivity to trastuzumab, murine proteins, or excipients, or to the adhesive of the SC device 12.History of severe allergic or immunological reactions, e.g. difficult to control asthma. 13.Pregnancy or lactation 14.Unable or unwilling to comply with the requirements of the protocol, as assessed by the investigator 15.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 16.Major surgical procedure or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipated need for major surgery during the course of study treatment. Patients must be free of any clinically significant sequalae of prior surgery before they can receive their first dose of study treatment. 17.More than 12 weeks between the end of the last chemotherapy cycle and the first dose of study treatment, in case these treatments are initiated s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

HER2-positive primary breast cancer
MedDRA version: 14.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Herceptin for SC injection
Product Code: Ro 045-2317/F07
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: Ro 045-2317/F07
Other descriptive name: rhuMAb HER2, Anti-HER
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-

Product Name: Herceptin for SC injection
Product Code: Ro 045-2317/F06
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: Ro 045-2317/F07
Other descriptive name: rhuMAb HER2, Anti-HER
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-

Primary Outcome(s)

Primary end point(s): Safety endpoints are the primary objectives in this study and will include: all AEs, Grade =3 AEs, SAEs, AEs leading to premature discontinuation of study treatment, AEs causing interruption of trastuzumab SC, cardiac AEs, CHF-related SAEs, premature withdrawals from study and study medication, exposure to treatment, laboratory parameters, LVEF, vital signs, ECG, weight, and ECOG performance status.

Main Objective: To assess the overall safety and tolerability of subcutaneous (SC) trastuzumab in HER2-positive early breast cancer (EBC) patients with assisted administration using a conventional syringe and needle (vial formulation) and with assisted administration with or without selfadministration using a single-use injection device (SID).

Secondary Objective: • Efficacy (both cohorts): - disease-free survival (DFS) - overall survival (OS) • Patient satisfaction with trastuzumab SC administration using the SID (patients in Cohort B who went on to self-administration of the study drug).

Timepoint(s) of evaluation of this end point: The primary analysis of the safety endpoints will take place when all patients have received 18 cycles of trastuzumab SC and have completed the Safety Follow-up assessments (4 weeks after their last dose of study treatment).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: A preliminary analysis of DFS and OS will be undertaken at the time of the primary safety analysis, i.e. when all patients have received 18 cycles.

Secondary end point(s): Secondary efficacy endpoints include DFS, OS (both cohorts) and patients' satisfaction with trastuzumab SC administration using the SID (Cohort B patients who went on to self administration only).

Secondary ID(s)

2011-005328-17-IE

MO28048

Source(s) of Monetary Support

F. Hoffmann-La Roche AG

Ethics review

Status: Approved
Approval date: 21/03/2012
Contact:

Results

• Results available: Yes
• Date Posted: 22/03/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005328-17/results