Breast Cancer
Conditions
Keywords
Large resectable breast cancer, Locally advanced breast cancer, Neoadjuvant therapy
Brief summary
2 different treatment schedules may be used for neoadjuvant chemotherapy in breast cancer using adriamycin, cyclophosphamide and taxotere. The most optimal sequence- concurrent or sequential- is however unclear. The aim of the study is to compare the efficacy and tolerability of neoadjuvant chemotherapy with AC followed by T(adriamycin, cyclophosphamide, taxotere) versus TAC ( with upfront T) in patient with large resectable or locally advanced breast cancer.
Interventions
DRUGDoxorubicin
doxorubicin (arm A:60 mg/m2) and arm B: 50 mg/m2)
DRUGCyclophosphamide
Cyclophosphamide: (arm A; 6000 mg/m2) an (arm B: 500 mg/m2)
DRUGDocetaxel
Docetaxel: (arm A: 100 mg/m2) and (arm B: 75 mg/m2)
Sponsors
Sanofi
Amgen
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Women presenting with large resectable or locally advanced breast cancer (T2 ≥3 cm, T3, or T4, and/or LN positive) * Measurable disease (breast and/or lymph nodes) * No prior surgery other than biopsy and no prior chemotherapy or radiation therapy * Age ≥18 years and age ≤70 years * Karnofsky Performance score ≥70% * Estrogen and/or progesterone receptor analysis performed on the primary tumour in the biopsy material * In case the tumor is ER/PgR ³ 50% positive, (neo)adjuvant hormonal therapy in stead of chemotherapy should be considered (e.g. in TEAM II study) * Her2/neu receptor analysis performed on the primary tumour in the biopsy material * Adequate bone marrow function (within 14 days prior to registration): WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l * Adequate liver function (within 4 weeks prior to start treatment): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL * Adequate renal function (within 4 weeks prior to start treatment): the calculated creatinine clearance should be ≥50 mL/min * Patients must be accessible for treatment and follow-up * Written informed consent according to the local Ethics Committee requirements
Exclusion criteria
* Patients with advanced pulmonary disease of any cause (oxygen dependent)- Peripheral neuropathy \> grade 2 whatever the cause * Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrythmias * Evidence of distant metastases (M1) * Patients with a history of breast cancer * Patients with a history of another malignancy (except basal cell skin carcinoma and carcinoma-in-situ of the uterine cervix) within 5 years of study entry- Pregnant or lactating women, or potentially fertile women not using adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The pathologic complete response rate to neoadjuvant chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| The tolerability (grade 3/4 CTC toxicities) of both chemotherapy regimens. | — |
| The clinical responses of neoadjuvant chemotherapy correlated to pathological responses after neoadjuvant chemotherapy. | — |
| The value of breast MRI in evaluating response to neoadjuvant chemotherapy as compared to clinical palpation, ultrasound techniques and histo-pathological outcome. | — |
| The false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy. | — |
| The delivered chemotherapy dose and dose-intensity of both chemotherapy regimens | — |
| The relation between pCR and DFS/OS. | — |
| The feasibility of the criteria for reporting pathological tumour response in surgical breast and axillary node resection specimens. | — |
| The prognostic and predictive value of tumour- and molecular markers, including ER, PgR, c-erbB2, microarray and other tumour characteristic analyses. | — |
| The disease-free and overall survival after 3 and 5 years follow-up. | — |
Countries
Netherlands
Outcome results
None listed