Cabazitaxel is a new taxoid which promotes the tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel and was selected for development based on a better antiproliferative activity on resistant cell lines than docetaxel. It has shown superior survival against mitoxantrone (MTX) plus prednisone in docetaxel pre-treated hormone refractory metastatic prostate cancer patients leading to registration of the compound. It showed a favorable toxicity profile with an interestingly low rate of alopecia. In the Genevieve study it will be compared against weekly paclitaxel which is currently most widely used treatment of breast cancer patients. A head-to-head comparison in the neoadjuvant setting will allow a rapid and precise comparison of efficacy and tolerability of cabacitaxel versus paclitaxel to decide in how far further development of this taxoid in breast cancer is reasonable.
Primary Objective To compare the pathologic complete response (pCR) rate in the breast (ypT0/is ypN0/+) in patients with operable Triple Negative or luminal B/HER2 normal breast cancer treated with either cabazitaxel or weekly paclitaxel. Secondary Objective To assess * pCR rates per arm separately for the stratified subpopulations. * Objective response rate (ORR) in the breast according to WHO criteria. * pCR rate defined as ypT0 ypN0. * pCR rate defined as ypT0/is ypN0. * pCR rate in the axillary lymph nodes (ypN0). * To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery. * Breast conservation surgery rate. * To assess the toxicity (NCI CTCAE V4.03) and compliance in both arms. * Invasive loco-regional recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS). * To explore the biomarkers and profiles potentially predicting response to treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
333
Cabazitaxel 25 mg/m² i.v. (Day 1) every 3 weeks (cycle) as 1-hour i.v infusion for a total of up to 4 cycles over a maximum total treatment period of 15 weeks before surgery
Paclitaxel 80 mg/m² as 1-hour i.v infusion. Patients will receive weekly (Days 1, 8, 15) paclitaxel administrations for a maximum of 12 infusions for a maximum of 4 cycles over a maximum total treatment period of 15 weeks before surgery (1 cycle = 3 weeks).
Luisenkrankenhaus
Düsseldorf, Germany
pathologic complete response (pCR) rate
Time frame: 15 months
pathologic complete response (pCR) rate separately for subpopulations
pathologic complete response (pCR) rate separately for stratified subpopulations
Time frame: 15 months
Objective response rate (ORR)
Time frame: 15 months
pCR rate defined as ypT0 ypN0
Time frame: 15 months
pCR rate defined as ypT0/is ypN0
Time frame: 15 months
pCR rate in the axillary lymph nodes (ypN0)
Time frame: 15 months
pCR rate in patients with a clinical complete response (cCR)
To determine the pCR rate in patients with a clinical complete response (cCR) and a negative core biopsy before surgery
Time frame: 15 months
local recurrence free survival (LRFS) in patients with a clinical complete response (cCR)
To determine the local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery
Time frame: 15 months
Breast conservation surgery rate
Time frame: 15 months
Toxicity
To assess the toxicity (NCI CTCAE V4.03) in both arms.
Time frame: 15 months
Compliance
To assess compliance in both arms.
Time frame: 15 months
Invasive loco-regional recurrence free survival (LRRFS)
Time frame: 15 months
Distant-disease-free survival (DDFS)
Time frame: 15 months
Invasive disease-free survival (IDFS)
Time frame: 15 months
Overall survival (OS)
Time frame: 15 months
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