Clinical trial NCT02194166: A Study to Investigate the Tolerability of Subcutaneous (SC) Trastuzumab Administration in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Early Breast Cancer (eBC) Using Either a Single-Use Injection Device or Manual Administration
Official title: An Open-Label, Randomized, Cross-Over, Multicenter, Phase IIIb Study, to Assess Patients' Tolerability of Trastuzumab Administrated Subcutaneously (SC) Either Via a Single Use Injection Device (SID) or Via Vial for Manual Administration (SC Vial) in Patients With HER2-Positive Early Breast Cancer (eBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-07-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This multicenter study in participants with HER2-positive eBC will investigate participants' pain and discomfort of SC trastuzumab (Herceptin) administered either via a single-use injection device (SID) or via vial for manual administration using a hand-held syringe (SC vial). In total, participants will obtain at least 18 cycles/1 year of trastuzumab (4 cycles of intravenous \[IV\] and 14 cycles of SC trastuzumab).


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Hormonal therapy allowed as per institutional guidelines
* Left ventricular ejection fraction (LVEF) of greater than or equal to (\>/=) 55 percent (%) measured by echocardiography (ECHO) prior to first dose of trastuzumab
* HER2-positive disease immunohistochemistry (IHC) 3+ or in-situ hybridization (ISH) positive as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
* Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
* No evidence of residual, locally recurrent or metastatic disease after completion of surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant)
* Participants who have completed all (neo)adjuvant treatment or participants after adjuvant chemotherapy with doxorubicin and cyclophosphamide (AC) to whom the 4 subsequent cycles of trastuzumab in combination with paclitaxel or docetaxel are indicated per local practice
* Not more than 3 months should have elapsed since the last dose of adjuvant chemotherapy in case of subsequent treatment scheme

Exclusion Criteria:

* Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent
* History of other malignancy that can affect compliance with the protocol or interpretation of results. Participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and participants with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible. Participants with previous ductal carcinoma in situ (DCIS) of the breast are also eligible for the study
* Participants with severe dyspnea at rest or requiring supplementary oxygen therapy
* Participants with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Prior maximum cumulative dose of doxorubicin \>360 mg/m2 or maximum cumulative dose of epirubicin \>720 mg/m2 or equivalent
* 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 enrollment in another clinical trial using an investigational anticancer 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®, or the adhesive of the SC device, or a history of severe allergic or immunological reactions, e.g., difficult to control asthma
* Inadequate bone marrow, hepatic, or renal function
* Major surgical procedure or significant traumatic injury within 14 days prior to the first dose of study treatment or anticipated need for major surgery during the course of study treatment

Primary outcomes:
measure: Participant Pain as Measured on a 10 Centimeter (cm) Visual Analogue Scale
timeFrame: Week 13 up to Week 52
measure: Participant Discomfort as Measured on a 10 cm Visual Analogue Scale
timeFrame: Week 13 up to Week 52
Secondary outcomes:
measure: Healthcare Professional Satisfaction With SC Formulation as Assessed by Health Care Professional Questionnaire (HCPQ)
timeFrame: Week 22
measure: Patient Satisfaction With SC Formulation as Assessed by Patients Satisfaction Questionnaire (PSQ)
timeFrame: Week 52
measure: Healthcare Professional Perceived Time Savings With SC Trastuzumab as Assessed by HCPQ
timeFrame: Week 22
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to approximately 3 years
measure: Overall Survival
timeFrame: From first study treatment to death from any cause, assessed up to approximately 4.5 years
measure: Disease-Free Survival, Assessed as per Institutional Practice or American Society of Clinical Oncology (ASCO) Adjuvant Follow-up Guidelines 2006
timeFrame: From first study treatment to documented disease progression or death, assessed up to approximately 3 years
measure: Number of Days on Trastuzumab Treatment
timeFrame: Week 1 up to Week 52
measure: Total Daily Dose of Trastuzumab
timeFrame: Week 1 up to Week 52
measure: Cumulative Dose of Trastuzumab
timeFrame: Week 1 up to Week 52
measure: Duration of Treatment
timeFrame: Week 1 up to Week 52
measure: Duration of Safety Observation
timeFrame: 28 days after last study treatment (up to Week 56)
measure: Duration of Follow-Up
timeFrame: 25 months after last study treatment (up to 3 years)
Other outcomes:
Locations:
city: A/g Lesnoy, Minsk Region
country: Belarus
facility: State Inst N.N. Alexandrov Republican Scientific & Practical Centre of Oncology & Medical Radiology
city: Brest
country: Belarus
facility: Healthcare Institution "Brest Regional Oncologic Dispensary"
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncologic Dispensary
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
city: Almaty
country: Kazakhstan
facility: Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department
city: Almaty
country: Kazakhstan
facility: Almaty Cancer Hospital; Chemotherapy department
city: Astana
country: Kazakhstan
facility: Oncology centre of Astana; Chemotherapy department
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: