Breast Cancer
Conditions
Brief summary
This single arm, open-label study will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with a taxane as first line therapy in participants with HER2-positive breast cancer who relapsed after neoadjuvant or adjuvant Herceptin treatment. Participants will receive Herceptin (loading dose of 4 mg/kg intravenously \[iv\], 2 mg/kg iv weekly thereafter) with 6 3-week cycles of either docetaxel (100 mg/m2 iv every 3 weeks) or paclitaxel (90 mg/m2 every week). Herceptin treatment will be continued until disease progression or unacceptable toxicity occurs.
Interventions
DRUGDocetaxel
100 mg/m2 iv every 3 weeks, 6 cycles (18 weeks)
DRUGPaclitaxel
90 mg/kg iv (+/-10%) every 3 weeks for 6 3-week cycles (18 weeks)
DRUGTrastuzumab
4 mg/kg iv loading dose on Day 1, 2 mg/kg iv on Day 8 and weekly thereafter
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female participants , \>/= 18 years of age * Locally recurrent/metastatic breast cancer (relapse in supra- or infraclavicular lymph nodes is regarded as metastatic disease) * HER2-positive primary disease * Participants must have received Herceptin in the adjuvant and/or neoadjuvant setting * Relapsed breast cancer \>/= 6 months after discontinuing last drugs of Herceptin and/or chemotherapy in the adjuvant and/or neoadjuvant setting for HER2-positive breast cancer * Measurable disease according to RECIST 1.0 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Maximum cumulative dose of doxorubicin \</= 360 mg/m2 or of epirubicin \</= 720 mg/m2 or no prior anthracyclines * At least 3 weeks after prior surgery or radiotherapy
Exclusion criteria
* Pregnant or breastfeeding women * Previous chemotherapy for metastatic breast cancer (prior endocrine therapy till progressive disease is allowed) * Pleural effusions, ascites or bone lesions as only manifestation of disease * Brain metastases * Invasive malignancy other than metastatic breast cancer * Inadequate bone marrow, hepatic or renal function * Prior treatment with anti-HER therapies other than (neo)adjuvant Herceptin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From the date of informed consent to the date of death or progressive disease (up to 28 months) | PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From the time of PR or CR until the date of PD or death (up to 28 months) | Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions. |
| Overall Survival | Time from enrollment to the date of death (up to 28 months) | Overall survival was defined as the time from the date of enrollment to the date of death due to any cause. |
| Percentage of Participants With an Adverse Event (AE) | Up to 28 days after last infusion of the study drug (28 months) | An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment. |
| Overall Response Rate | up to 28 months | Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. |
| Clinical Benefit Rate | up to 28 months | Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria. |
| Time to Progression | From the date of enrollment until the date of progressive disease (up to 28 months) | Time to progression was defined as the time from the date of enrollment until the date of progressive disease. |
| Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses) | up to 28 months | — |
Countries
China
Participant flow
Pre-assignment details
A total of 32 participants were enrolled in the study and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Participants with metastatic breast cancer received a loading dose of 4 milligrams per kilograms (mg/kg) of trastuzumab intravenously (IV) followed by 2 mg/kg of trastuzumab IV once a week along with docetaxel 100 milligrams per meter square (mg/m\^2), every 3 weeks or paclitaxel 90 mg/m\^2 once a week until progression of disease, occurrence of intolerable toxicity, the participant discontinues the study or dies. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participant did not Return for Treatment | 1 |
| Overall Study | Violated Selection Criteria | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Trastuzumab |
|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 11.61 |
| Gender Female | 32 Participants |
| Gender Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 32 |
| serious Total, serious adverse events | 5 / 32 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method.
Time frame: From the date of informed consent to the date of death or progressive disease (up to 28 months)
Population: Intention to treat (ITT) data set is defined as all the participants who are eligible through screening, register and enter the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Progression-Free Survival (PFS) | 9.9 months |
Secondary
Clinical Benefit Rate
Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria.
Time frame: up to 28 months
Population: ITT data set is defined as all the participants who are eligible through screening, register and enter the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Clinical Benefit Rate | 81.3 percentage of participants |
Secondary
Determination of Biomarkers Indicative for Response (Serum and Tumour Tissue Analyses)
Time frame: up to 28 months
Population: Biomarker analysis was not performed as the eligible biomarker sample quantity was too limited for testing.
Secondary
Duration of Response
Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions.
Time frame: From the time of PR or CR until the date of PD or death (up to 28 months)
Population: ITT data set is defined as all the participants who are eligible through screening, register and enter the study. Here, number of participants are the participants who had response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Duration of Response | 9.8 months |
Secondary
Overall Response Rate
Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions.
Time frame: up to 28 months
Population: ITT data set is defined as all the participants who are eligible through screening, register and enter the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Overall Response Rate | 81.3 percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the time from the date of enrollment to the date of death due to any cause.
Time frame: Time from enrollment to the date of death (up to 28 months)
Population: ITT data set is defined as all the participants who are eligible through screening, register and enter the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Overall Survival | NA months |
Secondary
Percentage of Participants With an Adverse Event (AE)
An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment.
Time frame: Up to 28 days after last infusion of the study drug (28 months)
Population: Safety population is defined as all enrolled participants and have taken at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Percentage of Participants With an Adverse Event (AE) | 93.8 percentage of participants |
Secondary
Time to Progression
Time to progression was defined as the time from the date of enrollment until the date of progressive disease.
Time frame: From the date of enrollment until the date of progressive disease (up to 28 months)
Population: ITT data set is defined as all the participants who are eligible through screening, register and enter the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Time to Progression | 9.9 months |