Clinical Trial Results:
HOMERUS: A Local, Open Label, Multicentre, Phase IIIB Study, Investigating Subcutaneous Trastuzumab Administered at Home With Single Injection Device in Patients With HER2-Positive Early Breast Cancer
Summary
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EudraCT number |
2013-000829-31 |
Trial protocol |
NL |
Global end of trial date |
14 Sep 2018
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Results information
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Results version number |
v1 |
This version publication date |
04 Oct 2019
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First version publication date |
04 Oct 2019
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Other versions |
v2 , v3 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ML28878
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +4161 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +4161 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Sep 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
A study to investigate subcutaneous trastuzumab administration at home with a Single Injection Device in subjects with HER2-positive early breast cancer.
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Protection of trial subjects |
Each subject or legally authorized representative signed an Informed Consent Form (ICF) before participating in this study.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Feb 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 125
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Worldwide total number of subjects |
125
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EEA total number of subjects |
125
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
115
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
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Pre-assignment
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Screening details |
Adult subjects With HER2-Positive Early Breast Cancer were included in this study. | ||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
Arms
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Arm title
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Trastuzumab | ||||||||||||||||||||
Arm description |
Participants will receive 600 milligrams (mg) trastuzumab SC by single-use injection device (SID) every 3 weeks (Q3W) for up to a total of 1 year, unless disease recurrence, unacceptable toxicity or participant withdrawal occurs. The first 3 administrations will be done at hospital, after that participants will be permitted to self-administer under the supervision of a healthcare professional (HCP). | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Trastuzumab
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Investigational medicinal product code |
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Other name |
Herceptin
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received 600 milligrams (mg) trastuzumab subcutaneously (SC) by a single-use injection device (SID) every 3 weeks (Q3W) for up to a total of 1 year, unless disease recurrence, unacceptable toxicity or participant withdrawal occurred. The first 3 administrations were done at hospital, after that participants were permitted to self administer under the supervision of a healthcare professional (HCP).
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Baseline characteristics reporting groups
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Reporting group title |
Trastuzumab
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Reporting group description |
Participants will receive 600 milligrams (mg) trastuzumab SC by single-use injection device (SID) every 3 weeks (Q3W) for up to a total of 1 year, unless disease recurrence, unacceptable toxicity or participant withdrawal occurs. The first 3 administrations will be done at hospital, after that participants will be permitted to self-administer under the supervision of a healthcare professional (HCP). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Trastuzumab
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Reporting group description |
Participants will receive 600 milligrams (mg) trastuzumab SC by single-use injection device (SID) every 3 weeks (Q3W) for up to a total of 1 year, unless disease recurrence, unacceptable toxicity or participant withdrawal occurs. The first 3 administrations will be done at hospital, after that participants will be permitted to self-administer under the supervision of a healthcare professional (HCP). |
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End point title |
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From Baseline up to approximately 4 years
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics are presented |
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No statistical analyses for this end point |
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End point title |
Pharmacokinetics Trough Concentrations (Ctrough) of Trastuzumab | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Pre-dose (within 1 day before trastuzumab administration) at Cycles 2, 3, 9, 10, 12, 13 (cycle length=21 days)
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Notes [2] - Final dataset is under investigation and the outcome will be posted once analysis is completed. |
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No statistical analyses for this end point |
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End point title |
Health Survey Short Form-36 (SF-36) Score | ||||||||||||||||
End point description |
SF-36 to assess Physical component score (PCS) and mental component score (MCS)
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End point type |
Secondary
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End point timeframe |
Cycles 3 and 9 (cycle length=21 days)
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No statistical analyses for this end point |
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End point title |
Mood and Anxiety Questionnaire (MASQ) Score | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Cycles 3 and 9 (cycle length=21 days)
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Choosing to Return to Hospital Administration | ||||||||||||||||||||||||||||||||
End point description |
According to protocol, patients should have been given the choice to return to in-hospital administration at cycle 6, however the patients deciding to do so made that decision later on during the study. Due to ethical considerations (patient well-fare), this could not be refused. Analyzing according to original endpoint would not reflect the actual course of the decision of patients to return to hospital administration. Therefore it was decided to analyse at later timepoints, deviating from the original endpoint.
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End point type |
Secondary
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End point timeframe |
Cycle 7 to Cycle 18 (cycle length=21 days)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline up to approximately 4 years
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Trastuzumab
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Reporting group description |
Participants will receive 600 milligrams (mg) trastuzumab SC by SID every 3 weeks (Q3W) for up to a total of 1 year, unless disease recurrence, unacceptable toxicity or participant withdrawal occurs. The first 3 administrations will be done at hospital, after that participants will be permitted to self-administer under the supervision of a healthcare professional (HCP). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Feb 2014 |
Exclusion criterion 10 (inadequate bone marrow function) was deleted. This criterion is used for (dis)continuation of chemotherapy, not for (dis)continuation of trastuzumab. Safety lab was determined at screening, but bone marrow function was not used for in/exclusion. The sample size was corrected from 150 to 128. Trastuzumab SC vials were added as IMP because vials were used as back-up in case of SID failure. Furthermore, a description on how to handle SID failure was added. Text was added to indicate that also HCP could return the SID to the hospital. Text was added to indicate that the ICF had to be signed within 28 days to first dose. Visit windows were added to Protocol Section 4.4.2.1, and the time point for completion of the questionnaires was clarified and a time window was added to Protocol Section 4.4.7. The option of paper questionnaires was added to Protocol Section 7.3. MRI was deleted as a method for left ventricular ejection fraction (LVEF) measurement because this is only done by echocardiography (ECHO) or multiple gated acquisition (MUGA). Time points for cardiac safety assessments were added to Protocol Section 5.1.2 following addition of an extra schedule of assessments (see below). A schedule of assessment for patients that received 6 cycles of trastuzumab prior to the study was added and time of assessments were corrected throughout the protocol. Further revisions to the schedule of assessments were made to clarify which assessments needed to be done at which time point, and a time window for PK sampling "within 1 day before administration" and a note [t] concerning hematology and chemistry were added. |
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29 Apr 2014 |
The time point for completion of the questionnaires was clarified and a time window was added in Protocol Section 3.9.4. In inclusion criterion 6, the text 'except for patients in the neo-adjuvant setting' was deleted because this study only included patients in the adjuvant setting, and the text ‘in combination with chemotherapy’ was added to be compliant with the guidelines for breast cancer therapy. In inclusion criterion 7, LVEF was adjusted from ≥55% to ≥50% in line with the Dutch guidelines for mamma care "mammacarcinoom richtlijn, 2.0", which states that LVEF needs to be 50%-55% shortly before start of trastuzumab. In inclusion 7 criterion, the text ‘Except in case patient received anthracycline treatment previously then documented results within an acceptable limit from a cardiac assessment within 14 days prior to enrolment.’ was added. A section on Adverse Events of Special Interest (AESI) was added. In the schedule of assessment, LVEF at Cycle 1 Day 1 was deleted due to the change in inclusion criterion 7; the LVEF occurred at screening within 14 days prior to enrolment for all patients that received anthracycline treatment previously and did not need to be repeated at Cycle 1 Day 1. |
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21 May 2015 |
The Multiplex Ligation-dependent Probe Amplification (MLPA) method was added as an additional test to determine HER2 status. The use of hormonal auterine devices (IUDs) was clarified in exclusion criterion 6. The time window for completion of the SF-36 en MASQ questionnaires was clarified (within one week after dosing at Cycles 3 and 9). |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |