Tailoring NEOadjuvant Therapy in Hormone Receptor Positive, HER2 Negative, Luminal Breast Cancer.

NCT ID: NCT03283384

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-15
• Study Completion Date: 2027-08-31

Brief Summary

The aim of this prospective, randomized, multicenter, open-label, phase II study is to test if chemotherapy can be replaced by the combination of ribociclib plus letrozole as a neo-adjuvant therapy for patients with non-metastatic primary luminal breast cancer.

Detailed Description

Based on Ki67 levels after two weeks of initial letrozole treatment in postmenopausal patients with hormone receptor positive, HER2 negative, stage II/III breast cancer, patients are either advised to continue letrozole treatment (if Ki67 <1%) or will be randomized between standard chemotherapy (AC-T) or ribociclib in combination with letrozole (if Ki67 ≥1%).

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Advise letrozole, treatment choice 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 advised to stay on letrozole treatment until surgery. However, treatment choice is free.

Group Type: OTHER

Letrozole

Intervention Type: DRUG

Letrozole 2.5 mg daily.

Chemotherapy

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)).

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

Dose dense AC-T chemotherapy: consisting of 4 cycles of AC (doxorubicin and cyclophosphamide at a dose of 60 and 600 mg/m² as an i.v. bolus, respectively) 2-weekly, plus G-CSF (6 mg once per cycle) 24-48 hr after chemotherapy, followed by cycles of T (4 cycles docetaxel 100 mg/m² 3-weekly or 12 cycles paclitaxel 80 mg/m2 weekly).

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 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)).

Group Type: EXPERIMENTAL

Ribociclib plus letrozole

Intervention Type: DRUG

Ribociclib 600 mg/day (days 1-21, q4 weeks) plus letrozole 2.5 mg daily (days 1-28, q4 weeks).

Interventions

Letrozole

Letrozole 2.5 mg daily.

Intervention Type: DRUG

Chemotherapy

Dose dense AC-T chemotherapy: consisting of 4 cycles of AC (doxorubicin and cyclophosphamide at a dose of 60 and 600 mg/m² as an i.v. bolus, respectively) 2-weekly, plus G-CSF (6 mg once per cycle) 24-48 hr after chemotherapy, followed by cycles of T (4 cycles docetaxel 100 mg/m² 3-weekly or 12 cycles paclitaxel 80 mg/m2 weekly).

Intervention Type: DRUG

Ribociclib plus letrozole

Ribociclib 600 mg/day (days 1-21, q4 weeks) plus letrozole 2.5 mg daily (days 1-28, q4 weeks).

Intervention Type: DRUG

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Philips Healthcare

INDUSTRY

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith R Kroep, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Sabine C Linn, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Gerrit-Jan Liefers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

A. E van Leeuwen-Stok, PhD

Role: STUDY_DIRECTOR

BOOG Study Center

Locations

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Ziekenhuisgroep Twente

Almelo, , Netherlands

Ziekenhuis Amstelland

Amstelveen, , Netherlands

Nederlands Kanker Instituut - Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Gelre Ziekenhuizen

Apeldoorn, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Stichting Reinier Haga Groep (Reinier de Graaf Gasthuis)

Delft, , Netherlands

Stichting Deventer Ziekenhuisgroep

Deventer, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

Groene Hart Ziekenhuis

Gouda, , Netherlands

Spaarne Gasthuis

Haarlem, , Netherlands

Ziekenhuis St. Jansdal

Harderwijk, , Netherlands

Tergooi Ziekenhuizen

Hilversum, , Netherlands

Westfriesgasthuis

Hoorn, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Canisius-Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Laurentius Ziekenhuis

Roermond, , Netherlands

Bravis Ziekenhuis

Roosendaal, , Netherlands

Antonius Ziekenhuis

Sneek, , Netherlands

Haaglanden Medisch Centrum

The Hague, , Netherlands

HAGA Ziekenhuis

The Hague, , Netherlands

Ziekenhuis Rivierenland

Tiel, , Netherlands

Elisabeth Tweesteden Ziekenhuis

Tilburg, , Netherlands

VieCuri Medisch Centrum

Venlo, , Netherlands

Streekziekenhuis Koningin Beatrix

Winterswijk, , Netherlands

Isala

Zwolle, , Netherlands

Countries

Netherlands

Related Links

https://www.boogstudycenter.nl/studie/286/neolbc.html

Information NEOLBC study on BOOG website (sponsor).

Other Identifiers

2017-000676-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BOOG-2017-01

Identifier Type: -

Identifier Source: org_study_id