Patients with primary breast cancer (now in neoadjuvant or adjuvant setting). MedDRA version: 20.0 Level: LLT Classification code 10006192 Term: Breast cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Abraxane
Product Name: there is a trade name
Product Code: there is a trade name
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-
Anti-HER
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures. 2. Histologically confirmed unilateral or bilateral primary carcinoma of the breast. 3. Age at diagnosis at least 18 years, female, and biologically not older than 65 years (but in any case not older than 70 years). 4. In case of adjuvant therapy: Adequate surgical treatment with histological complete resection (R0) of the invasive breast tumor. Choice of axilla surgery is up to the participating site. 5. Centrally confirmed ER/PgR/HER2 and Ki-67 status detected on surgical removed tissue (for adjuvant patients) or from core biopsy (for neoadjuvant patients). ER/PR positive is defined as = 1% stained cells and HER2 positive is defined as IHC 3+ in > 10% immunoreactive cells or FISH (or equivalent test) ratio = 2.0. Formalin-fixed, paraffin-embedded (FFPE) breast tissue has to be sent to the Institute of Pathology at the Charité Berlin prior to randomization. 6. High risk breast cancer as defined as: • HER2 positive or triple-negative tumors irrespective of nodal status or • Luminal B-like tumors (ER and/or PgR positive, HER2 negative, Ki-67 > 20%) with involved lymph nodes or • 4 or more involved lymph nodes. 7. Complete staging work-up within 3 months prior to randomization. All patients must have performed bilateral mammography, breast ultrasound, breast MRT (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRT and bone scan. In case of positive bone scan, bone X-ray (or CT or MRT) is mandatory. Other tests may be performed as clinically indicated. 8. Karnofsky Performance status index = 80%. 9. Estimated life expectancy of at least 10 years irrespective of the diagnosis of breast cancer. 10. Confirmed normal cardiac function by ECG and cardiac ultrasound (LVEF or shortening fraction) within 2 weeks prior to randomization. LVEF must be above 55%. 11. Laboratory requirements: Hematology • Absolute neutrophil count (ANC) = 2.0 x 109/L and • Platelets = 100 x 109/L and • Hemoglobin = 10 g/dL (= 6.2 mmol/L). Hepatic function • Total bilirubin = 1.5x above upper normal limits (UNL) and • ASAT (SGOT) and ALAT (SGPT) = 1.5x UNL and • Alkaline phosphatase = 2.5x UNL. Renal function • Creatinine = 1.25 UNL, • Creatinine Clearance > 30mL/min (if creatinine is above UNL, according to Cockroft-Gault). 12. Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential. 13. Complete baseline documentation must be submitted via MedCODES and approved by GBG Forschungs GmbH. 14. Patients must be available and compliant for central diagnostics, treatment and follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2886 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2886
Exclusion criteria
Exclusion criteria: 1. Patients with Luminal A-like tumors (ER and or PgR positive, HER2 negative and Ki-67 = 20%) and • if neoadjuvant: 3 months (optimal NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP > 160/90mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. 7. Evidence for infection including wound infections, HIV, hepatitis. 8. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent. 9. Pre-existing motor or sensory neuropathy of a severity = grade 1 by NCI-CTCAE version 4.0. 10. Other severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study. 11. Previous or concurrent treatment with: • concurrent chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (= 10mg methylprednisolone or equivalent) except inhalative corticoids. • concurrent sex hormones. Prior treatment must be stopped before study entry. • concurrent treatment with any investigational, not marketed drug within 30 days prior to study entry. • previous or concurrent anti-cancer therapy for any reason. 12. Absolute contraindications for the use of corticosteroids. 13. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment. 14. Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the invasive disease-free survival (IDFS) after neo- / adjuvant chemotherapy with EnPC or dtEC-dtD in patients with early node-positive or high-risk node-negative breast cancer.;Secondary Objective: • To compare overall survival (OS) between arms. • To compare distant disease-free survival (DDFS) between arms. • To compare locoregional relapse-free survival (LRRFS) between arms. • To compare local relapse-free survival (LRFS) between arms. • To compare regional relapse-free survival (RRFS) between arms. • To compare brain metastasis free survival (overall and in the subgroup of TNBC and HER2 positive separately) between arms. • To evaluate the compliance in arms. • To compare the safety between arms (including time to resolve neuropathy to grade 1). • To measure the side effects of taxanes. • To compare treatment effects by intrinsic subtypes; and by Ki-67 between arms. • To compare treatment effects by pN0/1, pN2 or pN3 in the adjuvant cohort. • To compare treatment effects by nodal status c/p N0/1, c/p N2; c/p N3 in the overall cohort. • To compare the pCR rates per arm in patients treated with neoadj. therapy. Further secondary objectives are noted in the protocol.;Primary end point(s): Invasive Disease Free Survival (DDFS);Timepoint(s) of evaluation of this end point: A time driven final efficacy analysis will be performed 45 months after end of accrual. At that time it is expected that 797 events have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): LRRFS, RRFS, LRFS, IDFS and OS are defined as the time period between randomization and first event and will be analyzed after the end of the study by referring to data from GBG patient’s registry. Curves will be estimated using the Kaplan-Meier method, based on the ITT population, and compared with a two-sided log-rank test. Univariate and multivariate Cox-proportional hazards model will be used to adjust hazard ratios for stratification factor and the above defined covariates and pCR Tolerability and Safety: Descriptive statistics for the 2 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped. The reason for termination includes aspects of efficacy (e.g. termination due to tumor progression), safety (e.g. termination due to adverse events) and compliance (e.g. termination due to patient's withdrawal of consent). Reasons for premature termination will be categorized according to the main reason and will be presented in frequency tables. Safety by toxicity grades is defined by the NCI-CTCAE v4.0. The quality of life will be assessed using EORTC QLC-C30 and FACT-Taxane. Translational research: Exploratory analyses will be performed to identify possible relationships between biomarkers and survival. Patients with missing biomarker data will not be included in the respective analysis. ;Timepoint(s) of evaluation of this end point: A time driven final efficacy analysis will be performed 45 months after end of accrual. At that time it is expected that 797 events have occurred. Two safety interim analyses are planned after 200 and 900 patients have completed chemotherapy There is no timepoint for the evaluation of the translational research. | — |
Countries
Germany
Contacts
Public ContactProjektmanager
GBG Forschungs GmbH
Outcome results
None listed