Breast Cancer
Conditions
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them after surgery may kill any tumor cells remaining after surgery. It is not yet known whether docetaxel is more effective than ixabepilone when given after surgery and combination chemotherapy in treating breast cancer. PURPOSE: This randomized phase III trial is studying giving combination chemotherapy followed by docetaxel or ixabepilone to compare how well they work in treating patients who have undergone surgery for nonmetastatic breast cancer.
Detailed description
OBJECTIVES: Primary * To evaluate the benefit from sequential administration of 3 courses of combination chemotherapy (FEC100) followed by 3 courses of ixabepilone versus docetaxel on the 5-year disease-free survival of women with nonmetastatic, poor-prognosis breast cancer. Secondary * To compare the 5-year distant metastasis-free survival. * To compare the 5-year event-free survival. * To compare the 5-year overall survival. * To compare the safety profiles for the two chemotherapy regimens. * To identify and/or validate predictive-gene expression profiles of clinical response/resistance to the two treatment regimens. * To bank frozen and fixed tumor and frozen serum prospectively for future translational studies in both genomics and proteomics (transcriptome and proteome analyses, tissue array analyses). * To compare the cost-effectiveness of these 2 regimens. * To compare the quality-of-life of patients treated with these 2 regimens. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, menopausal status (pre- vs post-menopausal), and tumor hormone-receptor status (triple-negative vs progesterone-receptor negative, HER negative, and estrogen-receptor \[ER\] positive). Patients are randomized to 1 of 2 treatment arms. * Docetaxel Arm: Patients receive epirubicin hydrochloride IV, fluorouracil IV, and cyclophosphamide IV every 3 weeks in courses 1-3 and docetaxel IV alone every 3 weeks in courses 4-6. * Ixabepilone Arm: Patients receive treatment in courses 1-3 as in arm I and ixabepilone IV alone every 3 weeks in courses 4-6. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also complete a quality of life questionnaire periodically. After completion of study treatment, patients are followed periodically for up to 10 years.
Interventions
DRUGcyclophosphamide
500 mg/m² every 3 weeks
DRUGDocetaxel
100 mg/m² every 3 weeks
DRUGepirubicin hydrochloride
100 mg/m² every 3 weeks
DRUGfluorouracil
500 mg/m² every 3 weeks
DRUGixabepilone
40 mg/m² every 3 weeks
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically proven invasive unilateral breast cancer (regardless of the type) * Initial clinical condition compatible with complete initial resection * No residual macro or microscopic tumor after surgical excision * Node-positive disease (i.e., positive sentinel node or positive axillary clearance) (N+) or node-negative disease (-) meeting the following criteria : * Stage II or III disease * pT \>20 mm (T1-4) * Patients must meet 1 of the following hormone-receptor criteria: * Node-positive patients: triple-negative\* tumor (HER2 negative, estrogen-receptor \[ER\] negative, and progesterone receptor \[PR\] negative) OR double-negative (HER2 negative, PR negative, and ER+) * Node-negative patients: triple-negative\* tumor only * NOTE: \*Hormone-receptor negativity is defined as ER \<10% and PR \<10% by IHC and HER2 negativity is defined as IHC 0-1+ OR IHC 2+ and FISH or CISH negative * Must be able to begin chemotherapy no later than day 49 after the initial surgery
Exclusion criteria
* Clinically or radiologically detectable metastases (M0) * Bilateral breast cancer or contralateral ductal carcinoma in situ * Any metastatic impairment, including homolateral subclavicular node involvement, regardless of its type * Any tumor ≥T4a (cutaneous invasion, deep adherence, inflammatory breast cancer) * HER 2 overexpression defined as IHC 3+ OR IHC 2+ and FISH or CISH positive * Any clinically or radiologically suspect and non-explored damage to the contralateral breast PATIENT CHARACTERISTICS: Inclusion criteria: * Female * Pre- or postmenopausal * ECOG performance status 0-1 * Peripheral neuropathy ≤grade 1 * Neutrophil count ≥2,000/mm³ * Platelet count ≥100,000/mm³ * Hemoglobin \>9 g/dL * AST and ALT ≤1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤2.5 times ULN * Total bilirubin ≤1.0 times ULN * Serum creatinine ≤1.5 times ULN * LVEF ≥50% by MUGA scan or echocardiography * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease-free Survival (DFS) | At 5 years | DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Disease-free Survival Events for Triple-negative Subgroup | At 5 years | DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with triple negative breast cancer only. |
| Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup | At 5 years | DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with ER+/PR-/HER2- breast cancer only. |
| Number of Distant Metastasis-free Survival Events for the Whole Population | At 5 years | The distant metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. |
| Number of Event-free Survival | At 5 years | The Event-free Survival is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or the date of second neoplasia, or the date of death from any cause, whichever occurs first. |
| Overall Survival | At 5 years | The overall survival is the length of time from randomization that patients enrolled in the study are still alive. |
Countries
Belgium, France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel 3 cycles of FEC100 (F and C, each at 500 mg/m², E 100 mg/m², every 3 weeks) followed by 3 cycles of D (100 mg/m² every 3 weeks)
Cyclophosphamide: 500 mg/m² every 3 weeks Docetaxel: 100 mg/m² every 3 weeks Epirubicin hydrochloride: 100 mg/m² every 3 weeks Fluorouracil: 500 mg/m² every 3 weeks | 398 |
| Ixabepilone 3 cycles of FEC100 (F and C, each at 500 mg/m², E 100 mg/m², every 3 weeks) followed by 3 cycles of Ixabepilone (40 mg/m² every 3 weeks);
Cyclophosphamide: 500 mg/m² every 3 weeks Epirubicin hydrochloride: 100 mg/m² every 3 weeks Fluorouracil: 500 mg/m² every 3 weeks Ixabepilone: 40 mg/m² every 3 weeks | 364 |
| Total | 762 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 55 | 49 |
| Overall Study | Disease progression | 1 | 1 |
| Overall Study | End of monitoring in US centers | 11 | 11 |
| Overall Study | Lost to Follow-up | 18 | 31 |
| Overall Study | Patient has moved | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Docetaxel | Ixabepilone | Total |
|---|---|---|---|
| Age, Continuous | 53.5 years | 53 years | 53 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Belgium | 92 participants | 74 participants | 166 participants |
| Region of Enrollment France | 294 participants | 277 participants | 571 participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 398 Participants | 364 Participants | 762 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 | 58 / 398 | 51 / 364 |
| other Total, other adverse events | 398 / 398 | 364 / 364 |
| serious Total, serious adverse events | 207 / 398 | 158 / 364 |
Outcome results
Primary
Percentage of Participants With Disease-free Survival (DFS)
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first
Time frame: At 5 years
Population: The DFS was analyzed in the intention-to-treat population: All subjects randomized to a treatment arm with or without treatment (N=762).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Percentage of Participants With Disease-free Survival (DFS) | 78.97 Percentage of participants |
| Ixabepilone | Percentage of Participants With Disease-free Survival (DFS) | 83.37 Percentage of participants |
p-value: 0.17595% CI: [0.59, 1.1]Log Rank
Secondary
Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with ER+/PR-/HER2- breast cancer only.
Time frame: At 5 years
Population: The DFS for ER+/PR-/HER2- subgroup was analyzed in all ER+/PR-/HER2- breast cancer participants randomized to a treatment arm with or without treatment (N=167).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup | 21 Events |
| Ixabepilone | Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup | 17 Events |
p-value: 0.650295% CI: [0.45, 1.63]Log Rank
Secondary
Number of Disease-free Survival Events for Triple-negative Subgroup
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with triple negative breast cancer only.
Time frame: At 5 years
Population: The DFS for triple-negative subgroup was analyzed in all triple negative breast cancer participants randomized to a treatment arm with or without treatment (N=586).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Number of Disease-free Survival Events for Triple-negative Subgroup | 69 Events |
| Ixabepilone | Number of Disease-free Survival Events for Triple-negative Subgroup | 50 Events |
p-value: 0.168795% CI: [0.53, 1.11]Log Rank
Secondary
Number of Distant Metastasis-free Survival Events for the Whole Population
The distant metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body.
Time frame: At 5 years
Population: The DFS was analyzed in the intention-to-treat population: All subjects randomized to a treatment arm with or without treatment (N=762).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Number of Distant Metastasis-free Survival Events for the Whole Population | 82.3 Events |
| Ixabepilone | Number of Distant Metastasis-free Survival Events for the Whole Population | 87.7 Events |
p-value: 0.066595% CI: [0.49, 1.02]Log Rank
Secondary
Number of Event-free Survival
The Event-free Survival is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or the date of second neoplasia, or the date of death from any cause, whichever occurs first.
Time frame: At 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Number of Event-free Survival | 77.46 Events |
| Ixabepilone | Number of Event-free Survival | 81.53 Events |
p-value: 0.14895% CI: [0.59, 1.08]Log Rank
Secondary
Overall Survival
The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
Time frame: At 5 years
Population: The OS was analyzed in the intention-to-treat population: All subjects randomized to a treatment arm with or without treatment (N=762).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel | Overall Survival | 87.00 percentage of participants |
| Ixabepilone | Overall Survival | 87.60 percentage of participants |
p-value: 0.896895% CI: [0.67, 1.42]Log Rank