Clinical trial NCT01926886: A Study of Subcutaneous At Home Administration of Trastuzumab (Herceptin) in Participants With Human Epidermal Growth Factor Receptor 2-positive (HER2+) Early Breast Cancer (eBC)
Official title: A Single Arm Multi-center Study Investigating the at Home Administration of Trastuzumab Subcutaneous Vial for the Treatment of Patients With HER2-positive Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-08-21
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm, multicenter study will evaluate the safety of assisted subcutaneous administration of trastuzumab in participants with HER2+ eBC. Participants who have completed the first 6 cycles of intravenous (IV) trastuzumab as part of the (neo)adjuvant treatment will be eligible to receive a further 12 cycles of trastuzumab in this study. Participants will receive IV trastuzumab at initial loading dose of 8 milligrams per kilogram (mg/kg) body weight (BW) for three-weekly (q3w) regimen and then recommended maintenance dose of 6 mg/kg BW q3w for the first 3 cycles (cycles 7-9) in hospital followed by subcutaneous (SC) administration of trastuzumab at a fixed dose of 600 mg q3w for next 3 cycles (Cycles 10-12) at hospital and SC administration of trastuzumab at a fixed dose of 600 mg q3w at home for the next 6 cycles (Cycles 13-18).


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
* HER2-positive disease immunohistochemistry (IHC)3+ or in situ hybridization (ISH) positive, in line with local reimbursement criteria and determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Hormonal therapy will be allowed as per institutional guidelines
* Left ventricular ejection fraction (LVEF) of greater than or equal to (\>/=) 50% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC, or, for those who were receiving trastuzumab when beginning the study, documented results within an acceptable limit from a cardiac assessment within 3 months prior to enrollment
* Participants have completed the first 6 cycles of trastuzumab IV as part of the (neo)adjuvant treatment
* No evidence of residual, locally recurrent or metastatic disease after completion of surgery and chemotherapy, (neo-adjuvant or adjuvant)
* Use of concurrent curative radiotherapy will be permitted

Exclusion Criteria:

* History of other malignancy which could affect compliance with the protocol or interpretation of results. Participants 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
* 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
* 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
* Women of childbearing potential and male participants with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment
* Concurrent enrollment 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, or a history of severe allergic or immunological reactions, e.g. difficult to control asthma
* Inadequate bone marrow, hepatic or renal function

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 45 months
Secondary outcomes:
measure: Number of Participants With Modalities Assessed Using Patient Satisfaction Questionnaire 1 (PSQ1): In-Hospital
timeFrame: Prior (0 hour) to first trastuzumab SC administration at Cycle 13 (cycle length =21 days)
measure: Number of Participants With Modalities Assessed Using Patient Satisfaction Questionnaire 2 (PSQ2): At Home
timeFrame: Prior (0 hour) to fifth trastuzumab SC administration at Cycle 17 (cycle length=21 days)
measure: Participant-reported Severity of Symptoms as Assessed by Monroe Dunaway Anderson Symptom Inventory (MDASI) Questionnaire
timeFrame: Prior (0 hours) to Cycles 7, 10, 13, 16 (Each cycle=21 days)
measure: Participant-reported Interference of Symptoms With Life as Assessed by MDASI Questionnaire
timeFrame: Prior (0 hours) to Cycles 7, 10, 13, 16 (Each cycle=21 days)
measure: Number of Participants With Modalities Assessed Using Patient Experience Questionnaires (PEX) - Part 1:In-Hospital
timeFrame: Prior (0 hours) to Cycle 12 (cycle length=21 days)
measure: Number of Participants With Modalities Assessed Using PEX - Part 2: At Home
timeFrame: 1 month after end of treatment (up to 10 months)
measure: Number of Health Care Professionals With Modalities Assessed Using Health Care Professional Questionnaire (HCPEX-1)
timeFrame: Prior (0 hours) to Cycle 12 (cycle length=21 days)
measure: Disease-Free Survival (DFS) as Assessed by Routine Clinical, Radiological and Laboratory Criteria
timeFrame: From start of treatment up to 45 months
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Onze Lieve Vrouwziekenhuis Aalst
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Brugge
country: Belgium
facility: AZ Sint Jan
city: Brussels
country: Belgium
facility: CHU St Pierre (St Pierre)
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: AZ Sint Lucas (Sint Lucas)
city: Gent
country: Belgium
facility: UZ Gent
city: Haine-Saint-Paul
country: Belgium
facility: CH Jolimont - Lobbes (Jolimont)
city: Liège
country: Belgium
facility: Clinique Saint-Joseph
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: CHR de Namur
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Turnhout
country: Belgium
facility: AZ Turnhout Sint Elisabeth
city: Beer Sheva
country: Israel
facility: Soroka Medical Center; Oncology Dept
city: Haifa
country: Israel
facility: Rambam Medical Center; Oncology
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Kfar-Saba
country: Israel
facility: Meir Medical Center; Oncology
city: Nahariya
country: Israel
facility: Western Galilee Hospital; Oncology-Nahariya
city: Petach Tikva
country: Israel
facility: Rabin MC; Davidof Center - Oncology Institute
city: Ramat Gan
country: Israel
facility: Chaim Sheba medical center, Oncology division
city: Rehovot
country: Israel
facility: Kaplan Medical Center; Oncology Inst.
city: Tel Aviv
country: Israel
facility: Sourasky / Ichilov Hospital; Dept. of Oncology
city: Zerifin
country: Israel
facility: Assaf Harofeh; Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Denys H, Martinez-Mena CL, Martens MT, D'Hondt RG, Graas ML, Evron E, Fried G, Ben-Baruch NE, Vulsteke C, Van Steenberghe MM. Safety and tolerability of subcutaneous trastuzumab at home administration, results of the phase IIIb open-label BELIS study in HER2-positive early breast cancer. Breast Cancer Res Treat. 2020 May;181(1):97-105. doi: 10.1007/s10549-020-05604-7. Epub 2020 Apr 2.