Patients with histological tumor residuals after preoperative anthracycline and taxane containing chemotherapy for primary breast cancer
Conditions
Interventions
Trade Name: Zometa 4 mg/5 ml
Product Name: zoledronic acid
Product Code: CGP 42446
Pharmaceutical Form:
Product Name: letrozole
Pharmaceutical Form: Film-coated tablet
Product Name: calcium carbon
Sponsors
GBG Forschungsgesellschaft mbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures; - Complete baseline documentation sent to GBG; - Prior preoperative chemotherapy for at least 4 cycles, of which at least two must contain a taxane and an anthracycline given within a clinical trial approved by the protocol board; - Completely resected unilateral or bilateral primary carcinoma of the breast with histologically detectable tumor residuals (ypT1-4) and or histologically confirmed involvement of axillary nodes (ypN1-3). Complete axillary clearance is mandatory, sentinel node biopsy alone is not allowed in node positive cases; - A maximum interval from date of axillary surgery to entering this trial of 3 years; - Age 18 years or older; - Karnofsky index >= 70%; - Life expectancy of at least 10 years, disregarding the diagnosis of cancer; - No clinical evidence of local recurrence or distant metastases. Complete staging work-up within 3 months prior to registration. All patients must have (bilateral) mammography or breast MRI, breast ultrasound, chest X-ray, ultrasound or CT scan of the liver, and bone scan (within 8 months). In case of a positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated; - Adequate renal and hepatic function (serum creatinine, bilirubin, and transaminases within 1.5 × upper normal range); - Tissue block centrally available for further biological tests; - Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating center. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Known hypersensitivity reaction to the investigational compound; - Prior postoperative chemotherapy; - Prior treatment with bisphosphonates since breast cancer surgery; - Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration and must implement adequate non-hormonal contraceptive measures during study treatment; - History of diseases with influence on bone metabolism, such as Paget’s disease of bone and primary hyperparathyroidism or osteoporosis requiring treatment at the time of study entry or considered likely to become necessary within the six months - Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study - Prior or concomitant secondary malignancy (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix) - Concurrent treatment with other experimental drugs or any other anti-cancer therapy; - Serum creatinine >= 3 mg/dl (265 micromol/L) - Corrected (adjusted for serum albumin) serum calcium concentration = 12.0 mg/dl (3.00 mmol/L) - Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry; - Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - to determine the event-free survival (EFS) after zoledronic acid for 5 years versus no postoperative treatment in patients with “chemo-insensitive” breast cancer (ypT1-4 and/or ypN1-3) after preoperative anthracycline/taxane containing chemotherapy;Secondary Objective: - to determine overall survival in both treatment arms - to determine the EFS with respect to the interval between surgery and randomization - to determine the bone-metastasis free-survival in both arms - to determine the toxicity of and compliance to zoledronic acid - to determine the predictive value of primary breast tumor response on the effect of postoperative treatment - to determine the prognostic impact of chemotherapy induced amenorrhea in premenopausal patients;Primary end point(s): The primary objective of this trial is to show that zoledronic acid will prolong the event-free survival (EFS) compared to no postoperative adjuvant treatment. The following assumptions are made: - According to the results published by Kuerer et al. on the EFS of patients with remaining tumor (ypT1-T4) in the breast and positive lymph nodes after preoperative chemotherapy, the EFS at 5 years is postulated to be 58%. - There will be an improvement of the hazard ratio of 37% to an EFS of 67.2 % for patients receiving zoledronic acid - The error rate for a false positive outcome (?) is set to 5%, using two-sided significance tests - The error rate for a false negative outcome (?) is set to 20%, i.e. the power of the trial is set to 80% for the difference of clinical interest - A common exponential drop-out rate of 5% - Accrual period of 48 months during which patients enter the study - Follow-up period from the end of accrual until the analysis of the data: approx. 48 months. - Randomization will be stratified according to the participating center, time interval between surgery and entering this trial (within 3 months, within 1 year, within 2 years, within 3 years). The total number of patients re | — |
Countries
Austria, Germany
Outcome results
None listed