Breast cancer mamma carcinoma
Conditions
Interventions
If low (=1%) Ki67 expression randomization between:
• Neo-adjuvant standard chemotherapy (control group)
• Neo-adjuvant ribociclib in combination with letrozol (intervention group)
Sponsors
BOOG Study Center
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Postmenopausal women presenting with histological proven (core biopsy material) hormone receptor positive (ER>=50%, PR any), HER2 negative, stage II/ III breast cancer. • Measurable disease (breast and/or lymph nodes) • WHO 0-2 • Adequate bone marrow function (within 4 weeks prior to registration): WBC>=3.0x10^9/l, neutrophils >=1.5 x 10^9/l, platelets >=100 x 10^9/l • Adequate liver function (within 4 weeks prior to registration): bilirubin =50 ml/min • Accessible for treatment and follow-up • Written informed consent Randomization specific: • Registration in the NEOLBC trial before 2 weeks biopsy • Use of letrozole • Outcome central Ki67 determination in two weeks biopsy available.
Exclusion criteria
Exclusion criteria: • Evidence of distant metastases (M1) • Previous invasive breast cancer • Prior chemotherapy, radiation therapy or hormonal therapy with the exception of patients who received letrozole grade 2, whatever the cause • Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate =450 msec. • Known hypersensitivity reaction to any of the components of the treatment (peanuts, soy) • Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. • Currently receiving any of the following substances and cannot be discontinued 7 days prior to randomisation: o Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, pomegranate and Seville oranges. o That have a known risk to prolong the QT interval or induce Torsades de Pointes. o That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. o Herbal preparations/medications, dietary supplements. • Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in CCCA (defined as Ki67 IHC | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: • Correlation between Ki67 IHC scored manually, IHC scored automatically (Vectra ® 3) and Ki67 mRNA. • Correlation between ER pathway activity at baseline, after two weeks letrozole and at surgery and clinical outcome. If sufficient sample is available additional pathway activities (such as PI3K and others) can be determined. • Difference in pathologic response (pCR and response according to Miller and Payne) between the randomized study arms*. • Change in tumor biology and biomarkers (ER, PR, HER2, Rb, Ki67) at baseline, after 2 weeks letrozole and at surgery. • Toxicity according to NCI CTCAE v4.03 all grades and grade III/IV*. • Correlation of tumor measurements between standard MRI (using RECIST 1.1) and palpation (largest diameter in cm) at baseline, after AC/before T or 8 weeks of definitive neoadjuvant therapy and pre-surgery. • Descriptive analysis of event free survival (EFS) and overall survival (OS) at 3 and 5 years. Side study endpoints: • Change in ERa DNA binding signatures (Chip-seq), and gene expression profiles (RNA-seq) between baseline and after 2 weeks letrozole. • Effect of ribociclib on the activation, proliferation and differentiation of T cells • (Anti)correlation between the delta Ki67 (baseline and 2 weeks letrozole) and estrogen/letrozole levels in the blood. * Indicates that the objective is not applicable to the group with a Ki67 of | — |
Countries
Netherlands
Outcome results
None listed