Breast Cancer in patients with operable Triple Negative or luminal B/HER2 normal patients MedDRA version: 17.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Jevtana
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: Cabazitaxel
CAS Number: 183133-96-2
Other descriptive name: CABAZITAXEL
Concentration un
Sponsors
GBG Forschungs GmbH (German Breast Group)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures. • Complete baseline documentation must be sent to GBG Forschungs GmbH. • Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint. • Tumor lesion in the breast with a palpable size of => 2 cm or a sonographical size of => 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. • Patients must be in the following stages of disease: - cT3 or - cT2 or - cT1c and cN+ or - cT1c and pNSLN+. • In patients with multifocal or multicentric breast cancer, the largest lesion should be evaluated. • Centrally confirmed triple negative or luminal B/HER2-normal subtype. ER- and PgR-negative defined as 14% Ki-67 stained cells. The formalin-fixed, paraffin-embedded (FFPE) breast tissue block from the diagnostic core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization. • Age => 18 years. • Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1 (see Appendix A). • Laboratory requirements: - Hemoglobin > 9.0 g/dL -Absolute neutrophil count > 1.5 x 109/L, - Platelet count > 100 x 109/L, - AST/SGOT and/or ALT/SGPT =65 years) yes F.1.3.1 Number of subjects for this age range 326
Exclusion criteria
Exclusion criteria: • Any prior treatment for primary breast cancer including radiation therapy • History of ipsi/ or contra-lateral invasive breast cancer • Locally advanced disease including N3 and metastatic disease • Patients in the following stages of disease are not allowed: - cT4 • Prior malignancy without being disease-free for more than 5 years (except carcinoma in situ of the cervix or other in situ cancer (e.g. bladder cancer) and adequately treated basal cell carcinoma of the skin. • Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (=6 months before enrolment), myocardial infarction, arterial thrombotic events (=6 months before enrolment), unstable angina pectoris, New York Heart Association (NYHA) = grade 2 congestive heart failure and/or hypertension, serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment, or not controlled by medication • Any severe acute or chronic medical condition which could impair the ability of the patient to participate to the study or to comply with the study procedures or interfere with interpretation of study results (such as significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures). • Active infection. • Sex hormones. Prior treatment must be stopped before study entry. • Inability and unwillingness to comply with study visits, treatment, testing, and to comply with the protocol. • Administration of any live virus vaccine within 8 weeks preceding study entry. • Use of any investigational agent within 30 days of administration of the first dose of study drug or concurrent treatment on another clinical trial • Requirement for radiation therapy concurrent with study anticancer treatment. Patients who require breast or chest wall radiation therapy after surgery are eligible • Pregnancy or breastfeeding women • Patients with childbearing potential who do not agree to use accepted and effective method of contraception (barrier methods, intrauterine contraceptive devices, sterilization) during the study treatment period and following a period of 6 months after the last study drug administration. • History of hypersensitivity (grade = 3) to polysorbate 80 or any study drugs or excipients • Concurrent or planned treatment with potent strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a two-week wash-out period is necessary for patients who are already on these treatments) (see Appendix 3) • Contraindications to the use of corticosteroid treatment • Symptomatic peripheral neuropathy grade = 2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.4.03
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main 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: • 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 ;Primary end point(s): - Primary efficacy endpoint is the pCR rate defined as the complete absence of invasive carcinoma on histological examination in the breast irrespective of lymph node involvement (ypT0/Tis, ypN0/+) at the time of definitive surgery and confirmed by independent blinded centralized histology report review. It will be assessed using all removed breast and lymphatic tissues from all surgeries. Patients in whom success cannot be determined (e.g. patients in whom histology is not evaluable) will be included in the denominator, i.e. these patients will affect the success rate in the same way as treatment failures. ;Timepoint(s) of evaluation of this end point: - After definitive surgery of all patients | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Secondary short-term efficacy endpoints (ypT0 ypN0; ypT0/is ypN0; ypT(any) ypN0) will be summarized as rates in each treatment group, two-sided 95% confidence intervals will be calculated according to Pearson and Clopper, and the continuity corrected Pearson ?2 test will be performed to evaluate the difference of rates in treatment arms; these tests are considered explorative. 2) Breast conservation rate defined as tumorectomy, segmentectomy or quadrantectomy 3) Clinical (c) and imaging (i) response will be assessed after the 2nd cycle and before surgery by physical examination and imaging tests. Sonography is the preferred examination, however, if sonography appears not to provide valid results or is not performed; other imaging tests will be considered with the following decreasing priority: MRI, mammography, computed tomogram. The same imaging method should be considered for the measurement before, during and after treatment. Tumor response is defined as either a partial response (PR) or complete response (CR) according to WHO criteria (see section 21.7). (CR) is defined as no evidence of disease in the breast using preferably ultrasound and/or MRI, or if not possible, mammography or physical examination. A reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more is defined as partial response (PR), an increase by 25% or more or a new lesion as progressive disease (PD), and the remaining scenarios as no change (NC). Lymphatic nodes are not taken into account. For defined categories of efficacy (complete, partial, stable, or progression), the proportion of patients with success will be determined and appropriate confidence intervals will be calculated. 4) LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event (see 15.5, Table 7) and will be analyzed after the end of the study by referring to data from GBG patient’s registry. Progre | — |
Countries
Germany
Contacts
Public ContactGenevieve
GBG Forschungs GmbH
Outcome results
None listed