Early primary breast cancer, hormone receptor positve or negative, HER2 negative, any nodal status
Conditions
Sponsors
Westdeutsche Studiengruppe GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients, age at diagnosis 18 - 75 years 2. Histological confirmed unilateral primary invasive carcinoma of the breast 3. Clinical cT1 (> 1 cm) - cT4 (if operable, inflammatory breast cancer is excluded) 4. HER2 over-expressing tumor confirmed by: 3+ by Immunohisto-chemistry (IHC) and/or HER2/neu gene amplification by fluorescence, chromogenic or silver in-situ hybridization [FISH, CISH or SISH; >6 HER2 gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of = 2.0] 5. Clinically node positive disease or node negative disease 6. No clinical evidence for distant metastasis (cM0) after conventional staging 7. Performance Status ECOG = 1 or KI = 80% 8. Baseline LVEF > 50% measured by echocardiography 9. Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients 10. The patient must be accessible for treatment and follow-up 11. Written informed consent including a written informed consent for shipping of tumor block for central pathology review and evaluation prior to the start of any study procedures 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 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity reaction to the compounds or incorporated substances 2. Known polyneuropathy grade = 2 3. Severe and relevant comorbidity that would interact with the application of cytotoxic agents or the participation in the study including active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment). 4. Prior malignancy with a disease-free survival of 2.0 x ULN1.5 mg/dl • Serum Bilirubin > 1.1 mg/dl • Alkaline phosphatase > 2.5 x ULN • ASAT and/or ALAT > 2.5 ULN • Albumin < 2.5 g/dl 13. Uncompensated cardiac function 14. Malabsorption syndrome, disease significantly affecting gastrointestinal function 15. Concomitant use of CYP3A4 inhibitors or inducers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To establish a dynamic test after three weeks of neo-adjuvant therapy, which discriminates between responders and non-responders at final surgery (defined as pathological complete response by no invasive patterns in the breast and lymph nodes);Secondary Objective: • Event free survival (EFS) and overall survival (OS) • Toxicity • Cost efficacy ;Primary end point(s): Primary endpoint: • pathological complete response (pCR) at final surgery;Timepoint(s) of evaluation of this end point: Final surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • EFS and OS 1. 95% confidence intervals for 3-year survival and 5-year survival I. for the study collective as a whole II. for subgroups with/without pCR III. for subgroups with/without biomarker response during neoadjuvant therapy IV. for subgroup with pCR and no further adjuvant treatment V. comparisons: subgroup with pCR and no further adjuvant treatment versus subgroup without pCR but receiving adjuvant treatment versus subgroup with pCR and further adjuvant treament 2. Log rank statistics will be provided for each subgroup comparison • Toxicity: 1. point estimate and 95% confidence intervals for all toxicities (upper bounds if no events are observed) • Cost effectiveness of early response testing: 1. Health economic estimate of the savings in medication costs resulting from discontinuation of (expensive) neoadjuvant treatment in patients who fail to exhibit early response (and thus who would not be likely to derive benefit from neoadjuvant therapy) compared to giving the drugs indiscriminately 2. Health economic estimate of cost per QALY for patients who receive full neo-adjuvant chemotherapy regime (assuming that early response is required to complete the regime) and achieve pCR, improved EFS, and improved OS • The primary biomarker test will be performed based on comparison of immunohistochemical measurement of Ki-67 in 2nd vs. 1st biopsy (“proliferation drop”). Proliferation drop is considered to be the key factor for predicting efficacy of the combination therapy;Timepoint(s) of evaluation of this end point: EFS and OS: three and five years after surgery | — |
Countries
Germany
Contacts
Public ContactStudienzentrale
Westdeutsche Studiengruppe GmbH
Outcome results
None listed