Tailoring NEOadjuvant Therapy in Hormone Receptor Positive, HER2 Negative, Luminal Breast Cancer. (NEOLBC)
Breast Neoplasms
About this trial
This is an interventional treatment trial for Breast Neoplasms focused on measuring Breast cancer, Ribociclib, Letrozole, Chemotherapy, CDK4, CDK6, Ki67, NEOLBC
Eligibility 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≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
- Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
- Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be ≥50 ml/min
- Accessible for treatment and follow-up
- Written informed consent
Inclusion criteria randomization specific:
In order to be eligible to be randomized in this study, a subject must meet all of the following criteria:
- Registration in the NEOLBC trial before 2 weeks biopsy
- Use of letrozole
- Outcome central Ki67 determination in two weeks biopsy available.
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 ≤ 14 days (+ max. 4 days) prior to registration and who are still on letrozole.
- Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
- Peripheral neuropathy > 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 <50 at rest) or QTcF ≥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:
- Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelo's, star-fruit, pomegranate and Seville oranges.
- That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
- 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.
Sites / Locations
- Jeroen Bosch Ziekenhuis
- Ziekenhuisgroep Twente
- Ziekenhuis Amstelland
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek
- Onze Lieve Vrouwe Gasthuis
- Gelre Ziekenhuizen
- Amphia Ziekenhuis
- Stichting Reinier Haga Groep (Reinier de Graaf Gasthuis)
- Haaglanden Medisch Centrum
- HAGA Ziekenhuis
- Stichting Deventer Ziekenhuisgroep
- Catharina Ziekenhuis
- Maxima Medisch Centrum
- Groene Hart Ziekenhuis
- Spaarne Gasthuis
- Ziekenhuis St. Jansdal
- Tergooi Ziekenhuizen
- Westfriesgasthuis
- Leiden University Medical Center
- Academisch Ziekenhuis Maastricht
- Canisius-Wilhelmina Ziekenhuis
- Laurentius Ziekenhuis
- Bravis Ziekenhuis
- Antonius Ziekenhuis
- Ziekenhuis Rivierenland
- Elisabeth Tweesteden Ziekenhuis
- VieCuri Medisch Centrum
- Streekziekenhuis Koningin Beatrix
- Isala
Arms of the Study
Arm 1
Arm 2
Arm 3
Other
Active Comparator
Experimental
Advise letrozole, treatment choice free.
Chemotherapy
Ribociclib plus letrozole
All patients initially start with two weeks of letrozole treatment. Patients with a Ki67 of <1% in the biopsy taken after those two weeks of treatment are advised to stay on letrozole treatment until surgery. However, treatment choice is free.
All patients initially start with two weeks of letrozole treatment. Patients with a Ki67 of ≥1% in the biopsy taken after those two weeks of treatment are randomized between chemotherapy (standard AC-T chemotherapy) or ribociclib plus letrozole (ribociclib 600 mg/day (days 1-21, q4 weeks) plus letrozole 2.5 mg daily (days 1-28, q4 weeks)).
All patients initially start with two weeks of letrozole treatment. Patients with a Ki67 of ≥1% in the biopsy taken after those two weeks of treatment are randomized between chemotherapy (standard AC-T chemotherapy) or ribociclib plus letrozole (ribociclib 600 mg/day (days 1-21, q4 weeks) plus letrozole 2.5 mg daily (days 1-28, q4 weeks)).