Chemotherapy De-escalation in HR +, HER2-, Intermediate-risk Early Breast Cancer Treated With Adjuvant Ribociclib

Recruiting now · Phase 3

Conditions studied: Breast Cancer

In brief

The advent of CDK4/6 inhibitors (drugs designed to block the action of CDK4/6 proteins, which play a key role in cell proliferation) has improved treatment prospects for patients with metastatic breast cancer whose tumour cells express hormone receptors but not the HER2 protein (HR+/HER2-). The NATALEE study showed that the addition of ribociclib for three years to conventional adjuvant hormone therapy (i.e. after surgery) prolonged survival free of invasive disease (i.e. extending to surrounding tissues) in patients with early HR breast cancer+ /HER2-. Unlike other studies, NATALEE included a group of patients at intermediate risk of recurrence, usually treated with adjuvant chemotherapy before receiving hormone therapy. However, the benefit of adjuvant chemotherapy in these patients is uncertain. The hypothesis of the NoLEEta study is that by using the CDK 4/6 inhibitor, patients could avoid adjuvant chemotherapy and therefore be spared the side-effects associated with this chemotherapy, without reducing the efficacy of the treatment.

Key facts

Study ID

NCT07237256

Run by

UNICANCER

People needed

3902

Starts

2025-12-18

Expected to finish

2037-12-31

Last updated by the study team

2026-05-26

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patient must have signed a written informed consent prior to any trial-specific screening procedure.
• Note: When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Patient is ≥ 18 years old.
• Patient is female with known menopausal status at the time of randomization.
• Post-menopausal status is defined as:
• Patient underwent bilateral oophorectomy, or
• Age ≥ 60 years, or
• Age < 60 years and either amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) or Follicle-stimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges.
• If taking tamoxifen or toremifene and age <60 years, then FSH and plasma estradiol level in postmenopausal ranges.
• The following criteria must be met for histologically confirmed invasive breast carcinoma, as determined by the local pathologist:
• Pathological stage (8th edition of the AJCC), including pT2 pN0 Grade 3 or pT2 pN0 Grade 2 with Ki67≥20% or pT0-2 pN1 or pT3-4 pN0
• ER-positive (with tumor cells showing ≥10% ER staining) and HER2-negative according to the most recent ASCO/CAP guidelines.
• Note: Multifocal and multicentric tumors are allowed if they meet the clinical stage II criteria of the 8th Edition of the AJCC. All tumors must be ER-positive and HER2-negative. Patients with bilateral invasive breast cancer (diagnosed simultaneously or within 6 months of each other) are eligible if all lesions tested on both sides are ER+ (ie, ≥10% positive stained cells) and HER2- AND adequate surgery has been performed in both breasts.
• Chemotherapy eligible per investigator decision, based on clinicopathological findings or the results of any genomic signature.
• Patient has no contraindication for the adjuvant endocrine therapy (ET) or chemotherapy in the trial and is planned to be treated with ET for 5 years (after randomization date) or more.
• Curative surgery for the invasive disease must have been performed with negative surgical margins within 12 weeks before randomization. If positive surgical margins, patients are eligible if revision surgery or other adequate local treatment (i.e local radiotherapy) is planned.
• Women of childbearing potential (CBP) must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment.
• Women of childbearing potential must agree to use one effective form of contraception during trial treatment and up to 21 days after the last dose of study drugs or longer, if required per standard of care;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 28 days prior to randomization.
• Adequate hematological, renal, and hepatic function, as outlined below:
• Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L
• Platelet count ≥100 x 10⁹/L
• Hemoglobin ≥9 g/dL
• Total bilirubin < ULN. Patients with known Gilbert syndrome may be enrolled with total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 x ULN

You may not qualify if…

• Patient has received any neoadjuvant chemotherapy since her breast cancer diagnosis or has received any prior CDK4/6 inhibitor.
• Breast cancer diagnosed while patient was receiving tamoxifen, raloxifene or aromatase inhibitors (AIs) for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last 2 years prior to randomization.
• Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy or peanut allergy).
• Patient with evidence or history of distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition), inflammatory breast cancer, breast cancer recurrence (local or distant) or a different primary breast cancer.
• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Note: Patients with adequately treated basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible.
• Patients whose breast cancer is considered as endocrine therapy insensitive, as determined by investigator's opinion; this may include (but is not limited to) breast cancer classified as " basal like " by molecular signatures (if available in the patient file) and/or breast cancer with persistently high proliferation after pre-operative endocrine therapy.
• Patient has had major surgery within 14 days prior to study treatment initiation.
• Patient has known history of human immunodeficiency virus (HIV) infection (testing is not mandatory) whose antiretroviral therapy (ART) has a known strong CYP3A4 inhibitor with potential for DDI with ribociclib. Patients with HIV may be enrolled if they fulfil the criteria recommended by FDA and ASCO guidelines (FDA Guidance, Uldrick et al. 2017):
• CD4+ T-cell (CD4+) counts ≥ 350 cells/µL, AND
• No history of AIDS-defining opportunistic infections within the past 12 months (prophylactic antimicrobials allowed if no drug-drug interactions or overlapping toxicities), AND
• On established ART which is not a strong CYP3A4 inhibitor, for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrolment. Effective ART is defined as a drug, dosage, and schedule associated with reduction and control of the viral load.
• Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to trial entry.
• Documented cardiomyopathy.
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory)
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment).
• Inability to determine the QTcF interval.
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block).
• Uncontrolled arterial hypertension with systolic blood pressure >160 mmHg.
• Presence of any other medical conditions, including respiratory or metabolic dysfunction, physical examination findings, or laboratory results that raise reasonable suspicion of a contraindication to the use of an experimental drug, potential impact on compliance with the study protocol, influence on result interpretation, or increased risk of treatment complications for the patients (such as severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, preexisting Crohn's disease or ulcerative colitis, or a preexisting chronic condition resulting in clinically significant diarrhea).
• Previous history of pneumonitis, regardless of cause.
• Patient is currently receiving any of the following substances within 7 days before randomization and which cannot be stopped within seven days prior to the start of treatment:

Where it is running

• Hospital Universitario de Jaén — Jaén, Spain (enrolling)
• Hospital Universitario Son Espases — Palma de Mallorca, Spain (enrolling)
• CHU de Saint Étienne — Saint-Etienne, France (enrolling)
• Hospital Universitario Clínico San Cecilio — Granada, Spain (enrolling)
• Hospital Universitario Arnau de Vilanova de Lleida — Lleida, Spain (enrolling)
• Hospital Universitario Virgen de la Arrixaca — Murcia, Spain (enrolling)
• Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace (GHRMSA) — Mulhouse, France (enrolling)
• Institut Curie — Saint-Cloud, France (enrolling)
• Institut Curie — Paris, Île-de-France Region, France (enrolling)
• Hospital Clínic de Barcelona — Barcelona, Spain (enrolling)
• ICO Hospitalet — L'Hospitalet de Llobregat, Spain (enrolling)
• Complejo Hospitalario Insular Materno-Infantil — Las Palmas de Gran Canaria, Spain (enrolling)
• Hospital de Mataró — Mataró, Spain (enrolling)
• Hospital Materno-Infantil Málaga — Málaga, Spain (enrolling)
• Centre Leon Berard — Lyon, France (enrolling)
• Centre de Cancerologie du Grand Montpellier — Montpellier, France (enrolling)
• Centre Antoine Lacassagne — Nice, France (enrolling)
• Institut Jean Godinot — Reims, France (enrolling)
• Institut Claudius Regaud — Toulouse, France (enrolling)
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy, France (enrolling)
• Hospital Universitario de Badajoz — Badajoz, Spain (enrolling)
• Hospital Vall d'Hebrón — Barcelona, Spain (enrolling)
• Sainte Catherine - Institut du Cancer Avignon Provence — Avignon, France (enrolling)
• Hospital Universitario de Jerez — Jerez de la Frontera, Spain (enrolling)
• Hospital Son Universitario Son Llatzer — Palma de Mallorca, Spain (enrolling)

Full record on ClinicalTrials.gov

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