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

Borstkanker Onderzoek Groep

Status and phase: Active, not recruiting; Phase 2

Conditions: Breast Neoplasms

Treatments: Drug: Letrozole; Drug: Ribociclib plus letrozole; Drug: Chemotherapy

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT03283384

2017-000676-29 (EudraCT Number)

BOOG-2017-01

Details and patient eligibility

About

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.

Full 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%).

Enrollment: 100 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 3 patient groups

Advise letrozole, treatment choice free.

Other group

Description:

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.

Treatment:

Drug: Letrozole

Chemotherapy

Active Comparator group

Description:

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)).

Treatment:

Drug: Chemotherapy

Ribociclib plus letrozole

Experimental group

Description:

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)).

Treatment:

Drug: Ribociclib plus letrozole