Back to resultsA Study of Subcutaneously Administered Herceptin (Trastuzumab) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (LISAH)
Primary Purpose
Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Trastuzumab - intravenous solution
Trastuzumab - subcutaneous solution
Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Female and male patients ≥ years of age.
- HER2-positive early breast cancer.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Hormonal therapy will be allowed as per institutional guidelines.
- Patients must be Herceptin (trastuzumab) naïve.
- Left ventricular ejection fraction (LVEF) of ≥ 55%.
- 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).
- 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. 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.
- Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.
- Patients 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 Herceptin, specifically, a 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), or diagnosed poorly controlled hypertension.
- Pregnant or lactating women.
- Women of childbearing potential and male patients 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 a history of severe allergic or immunological reactions, eg, difficult to control asthma.
- Inadequate bone marrow, hepatic, or renal function.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Trastuzumab - Thigh first, then upper arm
Trastuzumab - Upper arm first, then thigh
Arm Description
In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
Outcomes
Primary Outcome Measures
Quality of Life Score
Participants rated their quality of life on a visual analog scale (VAS) at the end of each cycle for Cycles 7-14. The left-end of the VAS represented the lowest-rated quality of life and the right-end of the VAS represented the highest-rated quality of life. Both the mean ratings for injections into the thigh and the upper arm and the minimum ratings for during injections into the thigh and the upper arm are reported. Quality of life scores ranged from 1 to 100 with a higher score indicating a better rated quality of life.
Secondary Outcome Measures
Overall Survival
Overall survival was defined as the time in months from Baseline to death from any cause.
Disease-free Survival
Disease-free survival was defined as the time in months from Baseline to disease recurrence or death, whichever occurred first.
Health Care Provider's Satisfaction With the Injection Site
The health care provider for each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.
Participant's Satisfaction With the Injection Site
Each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.
Percentage of Participants Preferring Each Injection Site
Participants were asked which of the 2 injection sites was their preferred site at the end of Cycle 14.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01928615
Brief Title
A Study of Subcutaneously Administered Herceptin (Trastuzumab) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer
Acronym
LISAH
Official Title
LISAH: An Open-label, Randomised Phase II Study Assessing Quality of Life Associated With Subcutaneous Trastuzumab Injected Into the Thigh or Upper Arm in Patients With HER2-positive Early Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Terminated
Why Stopped
Problems with drug supply
Study Start Date
September 2013 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label, randomized crossover study evaluated the quality of life, efficacy, and safety of subcutaneous Herceptin (trastuzumab) injected either into the thigh or the upper arm of participants with early HER2-positive breast cancer.
Detailed Description
In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase.
Following the run-in phase, participants were randomized to receive trastuzumab 600 mg subcutaneously every 3 weeks in the thigh and upper arm in a cross-over design for a total of 24 weeks (Cycles 7-14). They received trastuzumab either in the thigh first for 4 cycles (Cycles 7-10) followed by trastuzumab in the upper arm for 4 cycles (Cycles 11-14) or the upper arm first (Cycles 7-10) followed by the thigh (Cycles 11-14). For Cycles 15-18, participants could choose the injection site for trastuzumab 600 mg subcutaneously every 3 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trastuzumab - Thigh first, then upper arm
Arm Type
Experimental
Arm Description
In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
Arm Title
Trastuzumab - Upper arm first, then thigh
Arm Type
Experimental
Arm Description
In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
Intervention Type
Drug
Intervention Name(s)
Trastuzumab - intravenous solution
Other Intervention Name(s)
Herceptin, Ro 45-2317
Intervention Description
Trastuzumab was supplied as a powder to be reconstituted as a solution for intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab - subcutaneous solution
Other Intervention Name(s)
Herceptin, Ro 45-2317
Intervention Description
Trastuzumab was supplied as a solution for subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
Standard chemotherapy for early breast cancer.
Primary Outcome Measure Information:
Title
Quality of Life Score
Description
Participants rated their quality of life on a visual analog scale (VAS) at the end of each cycle for Cycles 7-14. The left-end of the VAS represented the lowest-rated quality of life and the right-end of the VAS represented the highest-rated quality of life. Both the mean ratings for injections into the thigh and the upper arm and the minimum ratings for during injections into the thigh and the upper arm are reported. Quality of life scores ranged from 1 to 100 with a higher score indicating a better rated quality of life.
Time Frame
Cycles 7-14 (Weeks 19-42, 24 weeks total)
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival was defined as the time in months from Baseline to death from any cause.
Time Frame
Baseline to the end of the study (up to 54 weeks)
Title
Disease-free Survival
Description
Disease-free survival was defined as the time in months from Baseline to disease recurrence or death, whichever occurred first.
Time Frame
Baseline to the end of the study (up to 54 weeks)
Title
Health Care Provider's Satisfaction With the Injection Site
Description
The health care provider for each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.
Time Frame
End of Cycles 10 and 14 (Weeks 30 and 42)
Title
Participant's Satisfaction With the Injection Site
Description
Each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.
Time Frame
End of Cycles 10 and 14 (Weeks 30 and 42)
Title
Percentage of Participants Preferring Each Injection Site
Description
Participants were asked which of the 2 injection sites was their preferred site at the end of Cycle 14.
Time Frame
End of Cycle 14 (Week 42)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female and male patients ≥ years of age.
HER2-positive early breast cancer.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Hormonal therapy will be allowed as per institutional guidelines.
Patients must be Herceptin (trastuzumab) naïve.
Left ventricular ejection fraction (LVEF) of ≥ 55%.
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).
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. 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.
Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.
Patients 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 Herceptin, specifically, a 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), or diagnosed poorly controlled hypertension.
Pregnant or lactating women.
Women of childbearing potential and male patients 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 a history of severe allergic or immunological reactions, eg, difficult to control asthma.
Inadequate bone marrow, hepatic, or renal function.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
12. IPD Sharing Statement
Learn more about this trial
A Study of Subcutaneously Administered Herceptin (Trastuzumab) in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer
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