Breast cancer HER2-positive breast cancer
Conditions
Interventions
This study has no intervention or control group. Patients will be treated
according to the above mentioned scheme (see *Study design*).
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Histologically confirmed primary invasive breast cancer 3. Stage II - IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter DCE-MRI >= 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology) 4. HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy 5. Known estrogen- and progesterone-receptor expression of the invasive tumor a. ER-negative or PR-negative is defined as = 18 years of age) 7. LVEF >=50% measured by echocardiography or MUGA 8. Eligible for neoadjuvant treatment 9. Laboratory requirements within 21 days prior to enrollment: a. Adequate bone marrow function (ANC >=1.5 x 109/l, platelets >=100 x 109/l); b. Adequate hepatic function (ALAT, ASAT and bilirubin =2.5 × the ULN range, if no evidence of biliary obstruction exists; c. Adequate renal function: creatinine clearance >50 ml/min estimated using the Cockcroft-Gault equation or MDRD equation, or based on a 24-hour urine collection measurement
Exclusion criteria
Exclusion criteria: 1. Current pregnancy or breastfeeding 2. Current or previous other malignancy unless treated without systemic therapy and more than five years ago 3. Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 4. Use of a strong CYP3A4 or CYP2C8 inhibitor within five half-lives of the inhibitor, or used a strong CYP3A4 or CYP2C8 inducer within five days prior to first dose of study treatment 5. Known chronic liver disease 6. History of inflammatory bowel disease or bowel resection 7. Contraindications for MRI 8. Inflammatory breast cancer, cT4 and/or cN3 tumors 9. Occult breast cancer (cT0) 10. Bilateral breast cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (all grades) until 30 days after last study treatment administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Incidence of serious adverse events until 30 days after last study treatment administration - Incidence of progressive disease during neoadjuvant treatment O progressive disease: defined as 20% increase *FTV or >20% increase measured in the longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET - Incidence of dose reductions and treatment discontinuations - Radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast - Pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall - Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall - Event-free survival (EFS) defined as the interval from registration to disease progression resulting in inoperability, recurrence, or death from any cause, whichever comes first at 3, 5 and 10 years after registration - Overall survival (OS) defined as the time from registration to death from any cause at 3, 5 and 10 years after registration | — |
Countries
Netherlands
Outcome results
None listed