A study to assess the safety of assisted- and self-administered subcutaneous trastuzumab as therapy in patients with operable Her2- positive early breast cancer

• Register: EUCTR
• Last refreshed on: 11 March 2020
• Main ID: EUCTR2011-005328-17-SI
• Date of registration: 31/05/2012
• Prospective Registration: No
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study to assess the safety of assisted- and self-administered subcutaneous trastuzumab as 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 selfadministered subcutaneous trastuzumab as therapy in patients with operable Her2-positive early breast cancer [SafeHer study] - SafeHer Study
• Date of first enrolment: 23/05/2012
• 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, 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, Lithuania, Malaysia, Mexico, Morocco, Netherlands, New Zealand, Pakistan, Panama, Peru, Philippines, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Arab Emirates, United Kingdom, Venezuela, Bolivarian Republic of, Vietnam

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent approved by the reviewing
independent Ethics Committee
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 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 a positive in situ
hybridization (ISH testing) by validate and approved methods within a
certified laboratory.
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. Examples
of adequate contraceptive measures are an intra-uterine device, a
barrier method (condoms, diaphragm) in conjunction with spermicidal
jelly, or total abstinence. Oral, injectable, or implant hormonal
contraceptives are not acceptable for females participating in the study.
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:
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 (including previous invasive
ipsilateral or contralateral breast cancer). Patients with curatively
treated carcinoma in situ of the cervix or basal cell carcinoma, and
patients with other curatively-treated malignancies, other than breast
cancer, who have been disease-free for at least 5 years, are eligible.
3. Past history of ductal carcinoma in situ (DCIS) within the last 5 years
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 treated with surgery only are
allowed to enter the study.
4. Metastatic disease
Haematological, Biochemical and Organ Function Related Criteria
5. Inadequate bone marrow function (as indicated by any of the
following):
• Total white blood cell count < 2,500 / mm3 (<2.5 x 10e9/L)
• Neutrophil count < 1,500 / mm3 (< 1.5 x 10e9/L)
• Platelets < 100,000 / mm3 (< 100 x 10e9/L)
• Haemoglobin < 10 g/dL
6. Impaired hepatic function (as indicated by any of the following):
• Serum total bilirubin > 1.5 x upper limit of normal (ULN)
• Alanine amino transferase > 2.5 x ULN
• Aspartate amino transferase > 2.5 x ULN
• Alkaline phosphatase > 2.5 x ULN
7. Impaired renal function: serum creatinine > 1.5 x ULN
Other Study Drug Related Exclusion Criteria
8. Serious cardiac illness or medical conditions including but not
confined to:
• History of documented heart failure or systolic dysfunction (LVEF <
50%)
• 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)• Angina pectoris requiring anti-anginal medication
• Clinically significant valvular heart disease
• Evidence of transmural infarction on electrocardiogram (ECG)
• Poorly controlled or uncontrolled hypertension (blood pressure
consistently over 140/90 mmHg, despite treatment), 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 a
general hypersensitivity to adhesives (Cohort B

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: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) 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 SC
CAS Number: 180288-69-1
Current Sponsor code: RO0452317
Other descriptive name: rhuMAb HER2, Anti-HER
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Product Name: Herceptin SC
Product Code: Ro 045-2317/F06
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TRASTUZUMAB SC
CAS Number: 180288-69-1
Current Sponsor code: RO0452317
Other descriptive name: rhuMAb HER2, Anti-HER
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

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).

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 self-administration using a single-use injection device (SID).

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.

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)

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).

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 of trastuzumab SC and have completed the Safety Follow-up
assessments (4 weeks after their last dose of study treatment). The final
analysis of OS and DFS will take place when the last patient has been
followed up for approximately 5 years after her/his last study treatment,
or earlier, if one of the following is documented for all treated patients:
withdrawal of consent, loss to follow-up or death.

Secondary ID(s)

MO28048

2011-005328-17-IE

Source(s) of Monetary Support

F.Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 17/04/2012
Contact:

Results

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