Primary breast cancer
Conditions
Interventions
Product Name: Capecitabine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Capecitabin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Product Name: T
Sponsors
German Breast Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures; 2. Complete baseline documentation sent to GBG Forschungs GmbH; 3. Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration 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; 4. Tumor lesion in the breast with a palpable size of >= 2 cm or a sonographically size of >= 1 cm in maximum diameter. The lesion has to be measurable in two-dimensions preferably by sonography. In case of inflammatory disease the extent of inflammation can be used as measurable lesion; 5. Patients should have stages of disease in which adjuvant chemotherapy would be considered. Therefore the following tumor stages are eligible: - Locally advanced tumors with cT4 or cT3 or - Estrogen (ER)- and progesterone (PgR)-receptor negative tumors or - ER or PgR positive tumors which are cN+ (for cT2) or pNSLN+ (for cT1) In patients with multifocal or multicentric breast cancer, the largest lesion should be measured; 6. Known Her-2/neu status measured by standardized IHC or if IHC 2+ by FISH on core biopsy 7. Age >= 18 years; 8. Karnofsky Performance status index >= 80%; 9. Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to registration. Results must be above the upper normal limit (UNL) of the institution; 10. Laboratory requirements: (within 21 days prior to registration) Hematology: Neutrophils >= 2.0 x 109/L and Platelets >= 100 x 109/L and Hemoglobin >= 10 g/dL Hepatic function: Total bilirubin 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study; Renal function: Creatinine = 50 mL/min; 11. Separate tissue block centrally available for further tests (except when the patient does not agree to central tissue banking) 12. Negative pregnancy test (urine or serum) within 14 days prior to registration for all women of childbearing potential; 13. Complete staging work-up within 3 months prior to registration. All patients must have bilateral mammography, breast ultrasound, breast MRI (optional), chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated; 14. Assessment on the intention why to perform NACT; 15. 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 or a cooperating 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: 1. Patients with low or moderate risk, who are only doubtful candidates for adjuvant chemotherapy and do not fulfill the inclusion criteria No. 5. 2. Evidence of distant metastasis; 3. Prior chemotherapy for any malignancy; 4. Prior radiation therapy for breast cancer; 5. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment; 6. Pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI criteria; 7. Other serious illness or medical condition: - Previous malignant disease with a disease-free survival of less than 5 years (except CIS of the Cervix and non-melanomatous skin cancer. - Congestive heart failure (>NYHA I) or unstable angina pectoris, previous history of myocardial infarction, uncontrolled arterial hypertension (more than 2 drugs) or high-risk uncontrolled arrhythmias; - History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent; - Currently active infection; - Active peptic ulcer - Unstable diabetes mellitus; insuline dependent type II diabetes mellitus - Inadaequate general condition (not fit for chemotherapy) 8. Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (<= 20 mg methylprednisolone or equivalent); 9. Definite contraindications for the use of corticosteroids; 10. Concurrent treatment with sex hormones. Prior treatment must be stopped before study entry 11. Concurrent treatment with virostatic agents like sorivudine or analogs like brivudine, concurrent treatment with aminoglycosides; 12. Concurrent treatment with other experimental drugs or any other anti-cancer therapy; 13. Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the pCR rates of neoadjuvant chemotherapy (NACT) with versus without Capecitabine and 8 versus 12 cycles in patients with primary breast cancer 2. To compare the pCR rate in patients with Her-2/neu positive tumors receiving Trastuzumab simultaneously to neoadjuvant chemotherapy (NACT) to patients with Her-2/neu negative tumors receiving neoadjuvant chemotherapy only ;Secondary Objective: To determine 1. the toxicity of and compliance to each treatment; 2. the (loco-regional and distant) disease-free and overall survival in each chemotherapy arm; 3. the (loco-regional and distant) disease-free and overall survival in patients with and without trastuzumab treatment; 4. the breast conservation rate after each treatment; 5. To assess the frequency of the use of sentinel node biopsy for selecting patients for NACT; 6. To compare the frequency of sentinel node biopsies at surgery after NACT in each arm; 7. the pCR rates for each treatment in the subgroup of patients with locally advanced (T4 a-d, N0-3, M0) breast cancer; 8. response rates at surgery (by imaging methods and by histopathological examination) in patient-subgroups according to their response after 4 x EC (CR, PR or NC); ;Primary end point(s): The primary endpoint for the comparison of neoadjuvant EC-Doc vs EC-DocX and EC-Doc-X (effect of X) and EC-Doc and EC-DocX vs EC-Doc-X (effect of time) is pCR. Using a two-sided test with ? = 0.05 and ? = 0.20, the calculated total sample size is 1500 patients. The primary endpoint for the comparison of patients with HER-2/neu positive tumors treated with trastuzumab (+TA, +TB, +TC) versus patients with HER-2/neu negative tumors (-TA, -TB, –TC) treated without trastuzumab is pCR. It is expected that approximately 30% of patients will have a HER-2/neu positive tumor. This is a non-randomised comparison. | — |
Countries
Germany
Outcome results
None listed