Breast Cancer
Conditions
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.
Interventions
DRUGTrastuzumab - intravenous solution
Trastuzumab was supplied as a powder to be reconstituted as a solution for intravenous infusion.
DRUGTrastuzumab - subcutaneous solution
Trastuzumab was supplied as a solution for subcutaneous injection.
DRUGChemotherapy
Standard chemotherapy for early breast cancer.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Score | Cycles 7-14 (Weeks 19-42, 24 weeks total) | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Baseline to the end of the study (up to 54 weeks) | Overall survival was defined as the time in months from Baseline to death from any cause. |
| Disease-free Survival | Baseline to the end of the study (up to 54 weeks) | 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 | End of Cycles 10 and 14 (Weeks 30 and 42) | 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 | End of Cycles 10 and 14 (Weeks 30 and 42) | 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 | End of Cycle 14 (Week 42) | Participants were asked which of the 2 injection sites was their preferred site at the end of Cycle 14. |
Countries
Austria
Participant flow
Pre-assignment details
Neither of the 2 enrolled participants were randomized to 1 of the 2 crossover treatment arms. Randomization would not have occurred until after Cycle 6. Both participants only received 1 cycle of treatment.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab 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). 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). 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). | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated by Sponsor | 2 |
Baseline characteristics
| Characteristic | Trastuzumab |
|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
Time frame: Cycles 7-14 (Weeks 19-42, 24 weeks total)
Population: Modified intent-to-treat population: All participants who received at least 1 dose of study medication and who have at least 1 quality of life score in each treatment period (Cycles 7-10 and Cycle 11-14).~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.
Secondary
Disease-free Survival
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)
Population: Intent-to-treat population: All participants who received at least 1 dose of study medication.~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.
Secondary
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.
Time frame: End of Cycles 10 and 14 (Weeks 30 and 42)
Population: Intent-to-treat population: All participants who received at least 1 dose of study medication.~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.
Secondary
Overall Survival
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)
Population: Intent-to-treat population: All participants who received at least 1 dose of study medication.~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.
Secondary
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.
Time frame: End of Cycles 10 and 14 (Weeks 30 and 42)
Population: Intent-to-treat population: All participants who received at least 1 dose of study medication.~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.
Secondary
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.
Time frame: End of Cycle 14 (Week 42)
Population: Intent-to-treat population: All participants who received at least 1 dose of study medication.~Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.