Breast Cancer
Conditions
Keywords
HER2 positive breast cancer, Metastatic breast cancer
Brief summary
Eligible patients must receive Caelyx plus Cyclophosphamide plus Herceptin for 6 cycles that will be administered every 4 weeks.
Detailed description
Sample size calculation will be done by means of Simon's method in 2 stages for phase II studies and will be based on the principal aim of the study (evaluation of the rate of objective response). The hypothesis brings over of the efficiency of the treatment it will be accepted if a rate of objective response of at least 55 % is obtained, rejecting the efficiency of the treatment when the rate of response targets be lower than 35 %. In this case, considering an alpha error of 0.05 and 80 % power, 14 patients will be included in the first stage; the study would continue if more than 5 objective responses were found. The total number of patients to including in the study would be 44. The results will be significant if they find at least 20 objective responses. Assuming a drop-out rate of 10 %, the total number of patients needed is 49 patients.
Interventions
DRUGLiposomal Doxorubicin
DRUGCyclophosphamide
DRUGTrastuzumab
Sponsors
Schering-Plough
Spanish Breast Cancer Research Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must sign an informed consent before of specific procedures of clinical trial. * Patients with histologically confirmed breast cancer and overexpression of Her2neu. * Age\> 18 years. * Eastern Cooperative Oncology Group (ECOG) equal or \< 2. * Patients have not been treated previously with chemotherapy for metastatic disease. * Patients must have at least one measurable lesion according to RECIST criteria. * Patients should have an adequate organ function to tolerate chemotherapy.
Exclusion criteria
* Patients with hypersensitivity reactions to any of the medications of the clinical trial. * Patients who are pregnant or lactating are not eligible. * Hepatic disease. * Not controlled active infection * Symptomatic metastatic brain cancer * Previous adjuvant treatment with anthracyclines with a total accumulated dose \> 300 mg/m2 (Doxorubicin) or \> 600 mg/m2 (Epirubicin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to cycle 6 (24 weeks) | ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | Through study treatment, and follow up period, assessed up to 88 weeks | TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Time to Treatment Failure (TTF) | Through study treatment, and follow up period, assessed up to 88 weeks | TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first. |
| Response Duration | Through study treatment, and follow up period, assessed up to 88 weeks | Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred. |
| Overall Survival (OS) | Through study treatment, and follow up period, assessed up to 88 weeks | OS was defined as the time elapsed from first treatment until death from any cause. |
Countries
Spain
Participant flow
Recruitment details
Between February 2006 and June 2008, 49 patients were enrolled at 12 Spanish sites. One patient never received treatment due to early death from progressive disease and was not included in this analysis.
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab Liposomal Doxorubicin 50 mg/m2 every 4 weeks for six cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for six cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg)
Liposomal Doxorubicin
Cyclophosphamide
Trastuzumab | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression | 7 |
| Overall Study | Mistake | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Liposomal Doxorubicin,Cyclophosphamide,Trastuzumab |
|---|---|
| Age, Continuous | 57 years |
| Disease stage at diagnosis Stage I to III | 26 Participants |
| Disease stage at diagnosis Stage IV | 22 Participants |
| Eastern Cooperative Oncology Group (ECOG) ECOG 0 | 26 Participants |
| Eastern Cooperative Oncology Group (ECOG) ECOG 1 | 20 Participants |
| Eastern Cooperative Oncology Group (ECOG) ECOG 2 | 2 Participants |
| Hormonal receptor status Negative | 24 Participants |
| Hormonal receptor status Positive | 24 Participants |
| Menopausal Status Postmenopausal | 39 Participants |
| Menopausal Status Premenopausal | 9 Participants |
| Number of disease sites 1 disease site | 10 Participants |
| Number of disease sites 2 disease sites | 18 Participants |
| Number of disease sites 3 disease sites or more | 20 Participants |
| Prior neo(adjuvant) chemotherapy Non Prior neo(adjuvant) chemotherapy | 25 Participants |
| Prior neo(adjuvant) chemotherapy Prior neo(adjuvant) chemotherapy | 23 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 48 |
| other Total, other adverse events | 48 / 48 |
| serious Total, serious adverse events | 16 / 48 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR.
Time frame: Up to cycle 6 (24 weeks)
Population: 49 patients included but 1 is not considered due to not receive any treatment and died before start
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Caelyx,Cyclophosphamide,Trastuzumab | Objective Response Rate (ORR) | 33 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time elapsed from first treatment until death from any cause.
Time frame: Through study treatment, and follow up period, assessed up to 88 weeks
Population: 49 patients included but 1 is not considered due to not receive any treatment and died before start
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caelyx,Cyclophosphamide,Trastuzumab | Overall Survival (OS) | 34.2 Months |
Secondary
Response Duration
Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred.
Time frame: Through study treatment, and follow up period, assessed up to 88 weeks
Population: Patients with Overall Response (see ORR objective)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caelyx,Cyclophosphamide,Trastuzumab | Response Duration | 9.51 Months |
Secondary
Time to Progression (TTP)
TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Through study treatment, and follow up period, assessed up to 88 weeks
Population: 49 patients included but 1 is not considered due to not receive any treatment and died before start
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caelyx,Cyclophosphamide,Trastuzumab | Time to Progression (TTP) | 12 Months |
Secondary
Time to Treatment Failure (TTF)
TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first.
Time frame: Through study treatment, and follow up period, assessed up to 88 weeks
Population: 49 patients included but 1 is not considered due to not receive any treatment and died before start
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Caelyx,Cyclophosphamide,Trastuzumab | Time to Treatment Failure (TTF) | 9.7 Months |