Breast Cancer
Conditions
Brief summary
This single arm study stratified patients into two treatment cohorts based on HER2-neu overexpression/amplification. Each cohort will be independently powered for the primary endpoint. The study will evaluate the efficacy, safety and impact on quality of life of treatment with oral Xeloda plus intravenous (iv) Taxotere (docetaxel). Patients with HER2-neu negative breast cancer will receive chemotherapy alone with oral Xeloda plus intravenous (iv) Taxotere (docetaxel). Patients with HER2-neu positive breast cancer, will receive the same chemotherapy in combination with intravenous (iv) Herceptin (trastuzumab). Patients will receive 3-weekly cycles of treatment with Xeloda (825mg/m2 oral administration \[po\] twice daily (bid) on days 1-14) + Taxotere (75mg/m2 iv on day 1). HER2-neu positive patients will also receive Herceptin (loading dose of 4mg/kg iv followed by 2mg/kg iv weekly). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGcapecitabine [Xeloda]
825mg/m2 po bid on days 1-14 of each 3 week cycle
DRUGTaxotere
75mg/m2 iv on day 1 of each 3 week cycle
DRUGHerceptin (HER2-neu positive patients only)
4mg/kg iv (loading dose) followed by 2mg/kg iv weekly
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* women \>=18 years of age; * newly diagnosed; * infiltrating (invasive) HER2-neu-negative or HER2-neu-positive breast cancer.
Exclusion criteria
* evidence of metastatic disease, except ipsilateral (same side) axillary lymph nodes; * previous systemic or local primary treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery | at the time of definitive surgery; after four 3-week cycles (3-4 months) | Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Near pCR (npCR) was defined as the presence of invasive tumor cells with a size of 5 mm or less in aggregate in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Only pathological assessments occurring prior to the first date of adjuvant treatment were included in the analysis of pCR rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery | at the time of definitive surgery; after four 3-week cycles (3-4 months) | Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. |
| Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR)) | post 2 and 4, 3-week cycles of treatment | The best overall response in an individual patient, according to RECIST, during preoperative treatment was the best response recorded from the start of study treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the baseline assessment) or completion of preoperative treatment. Patients with CR or PR were considered responders. Patients with no tumor assessment after the start of study treatment were considered nonresponders. |
| Percentage of Participants With Local Recurrence | 30 - 1102 days | Local recurrence was defined as evidence of recurrent carcinoma in the same breast where it was diagnosed initially before preoperative treatment. |
| Participants With Disease-Free Survival | 30 - 1102 days | Disease-free survival was defined as the time from date of surgery to date of first evidence of cancer recurrence in the breast (ie, local or distant recurrence or contra lateral disease) or death from any cause, whichever came first. Patients who were alive or withdrawn from the study and had no evidence of disease recurrence and for whom there was CRF evidence that evaluations had been made were censored at the date of the last clinical follow-up assessment when the patient was known to be disease free. |
| Participants With Overall Survival | 22 - 1191 days | Overall survival was defined as the time from date of start of study treatment to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Patients without follow-up assessment were censored at the day of the last dose. Patients with no post-baseline information were censored at the start of study treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HER2-Neu Negative Dose and route per treatment cycle (Q3W):
Capecitabine: 825 mg/m2, orally, twice daily, days 1-14 Docetaxel: 75 mg/m2, IV infusion, day 1
HER2-neu negative: capecitabine + docetaxel
Duration: Four 3-week treatment cycles | 122 |
| HER2-Neu Positive Dose and route per treatment cycle (Q3W):
Capecitabine: 825 mg/m2, orally, twice daily, days 1-14 Docetaxel: 75 mg/m2, IV infusion, day 1 Trastuzumab: loading dose 4 mg/kg, 90-min IV infusion; thereafter, 2 mg/kg, 30-min IV infusion, weekly
HER2-neu positive: capecitabine + docetaxel + trastuzumab
Duration: Four 3-week treatment cycles | 34 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Randomized but not dosed | 1 | 0 |
Baseline characteristics
| Characteristic | HER2-Neu Negative | HER2-Neu Positive | Total |
|---|---|---|---|
| Age Continuous | 51.0 years STANDARD_DEVIATION 11.2 | 52.2 years STANDARD_DEVIATION 9.36 | 51.3 years STANDARD_DEVIATION 10.79 |
| Sex: Female, Male Female | 122 Participants | 34 Participants | 156 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 121 / 122 | 33 / 34 |
| serious Total, serious adverse events | 15 / 122 | 7 / 34 |
Outcome results
Primary
Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery
Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Near pCR (npCR) was defined as the presence of invasive tumor cells with a size of 5 mm or less in aggregate in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Only pathological assessments occurring prior to the first date of adjuvant treatment were included in the analysis of pCR rate.
Time frame: at the time of definitive surgery; after four 3-week cycles (3-4 months)
Population: Pathological Response Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery | 15.8 percentage of participants |
| HER2-Neu Positive | Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery | 50.0 percentage of participants |
Secondary
Participants With Disease-Free Survival
Disease-free survival was defined as the time from date of surgery to date of first evidence of cancer recurrence in the breast (ie, local or distant recurrence or contra lateral disease) or death from any cause, whichever came first. Patients who were alive or withdrawn from the study and had no evidence of disease recurrence and for whom there was CRF evidence that evaluations had been made were censored at the date of the last clinical follow-up assessment when the patient was known to be disease free.
Time frame: 30 - 1102 days
Population: The analysis was done on the Postoperative Response Evaluable Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Participants With Disease-Free Survival | 92 participants |
| HER2-Neu Positive | Participants With Disease-Free Survival | 25 participants |
Secondary
Participants With Overall Survival
Overall survival was defined as the time from date of start of study treatment to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Patients without follow-up assessment were censored at the day of the last dose. Patients with no post-baseline information were censored at the start of study treatment.
Time frame: 22 - 1191 days
Population: The analysis was done on the post-operative Response Evaluable Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Participants With Overall Survival | 118 participants |
| HER2-Neu Positive | Participants With Overall Survival | 32 participants |
Secondary
Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery
Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment.
Time frame: at the time of definitive surgery; after four 3-week cycles (3-4 months)
Population: Pathological Response Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery | 9.9 percentage of participants |
| HER2-Neu Positive | Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery | 35.7 percentage of participants |
Secondary
Percentage of Participants With Local Recurrence
Local recurrence was defined as evidence of recurrent carcinoma in the same breast where it was diagnosed initially before preoperative treatment.
Time frame: 30 - 1102 days
Population: Postoperative Response Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Percentage of Participants With Local Recurrence | 3.1 percentage of participants |
| HER2-Neu Positive | Percentage of Participants With Local Recurrence | 3.7 percentage of participants |
Secondary
Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR))
The best overall response in an individual patient, according to RECIST, during preoperative treatment was the best response recorded from the start of study treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the baseline assessment) or completion of preoperative treatment. Patients with CR or PR were considered responders. Patients with no tumor assessment after the start of study treatment were considered nonresponders.
Time frame: post 2 and 4, 3-week cycles of treatment
Population: Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2-Neu Negative | Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR)) | 23.8 percentage of participants |
| HER2-Neu Positive | Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR)) | 23.5 percentage of participants |