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AzTrials

Breast CancerPhase 3NoLEEtaNCT07237256

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

A Phase 3 study testing Chemotherapy followed by endocrine therapy and ribociclib treatment and De-escalation in people with Breast Cancer, run by UNICANCER at 138 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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-). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Chemotherapy followed by endocrine therapy and ribociclib treatment and De-escalation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,902 participants
Where
138 sitesin 5 countries
Study dates
18 Dec 2025to 31 Dec 2037
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/min/1.73m² (CKD-EPI equation (2021))
  • Potassium, total calcium (corrected for serum albumin), and magnesium should be within institutional normal limits or corrected to within normal limits using supplements before the first dose of study medication.
  • Standard 12-lead ECG values assessed, as:
  • QTcF interval (QT interval using Fridericia's correction) at screening < 450 milliseconds (msec)
  • Resting heart rate 50-100 beats per minute (determined from the ECG)
  • Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
  • Absence of any psychological, familial or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • Patients must be affiliated to a Social Security System (or equivalent) based on local regulations.

Who cannot join

  • 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.
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  • 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:
  • Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummelos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5
  • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • Any medication prohibited according to the instructions for goserelin, leuprolide or triptorelin (pre-menopausal patients), anastrozole, exemestane, letrozole, or ribociclib.
  • Medications known to have a risk of prolonging the QT interval or causing Torsades de Pointes.
  • Patient is concurrently using hormone replacement therapy. Estrogen replacement therapy discontinued less than two weeks prior to the start of treatment.
  • Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment.
  • Note: The following uses of corticosteroids are permitted: a short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular).
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years.
  • Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the sponsor is required to establish eligibility.
  • Inability or unwillingness to swallow oral pills.
  • Presence of malabsorption syndrome or any other condition that could hinder the absorption of study drugs in the gastrointestinal tract.
  • Any psychological, familial, sociological, or geographical factors that may impede adherence to the study protocol and follow-up schedule.
  • Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the first 48 months of adjuvant therapy.
  • Persons deprived of their liberty or under protective custody or guardianship.

Trial locations and contacts

138 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Sandrine Marques contact

+33 (0) 6 17 90 00 54

s-marques@unicancer.fr

138 sites in 5 countries

France70 sites, 51 recruiting

  • Clinique de l'Europe

    Amiens, 80090

    Not yet recruiting

  • Institut de Cancérologie de l'Ouest - Site Paul Papin

    Angers, 49055

    Not yet recruiting

  • CH Victor Dupouy

    Argenteuil, 95107

    Not yet recruiting

  • CH Henri Mondor

    Aurillac, 15000

    Active, not recruiting

  • Centre Hospitalier d'Auxerre

    Auxerre

    Not yet recruiting

  • Sainte Catherine - Institut du Cancer Avignon Provence

    Avignon, 84918

    Recruiting

  • Centre Hospitalier de la Cote Basque

    Bayonne, 64100

    Active, not recruiting

  • Centre Hospitalier Simone Veil de Beauvais

    Beauvais, 60021

    Active, not recruiting

  • Centre Hospitalier Universitaire de Besancon

    Besançon, 25000

    Not yet recruiting

  • Institut Bergonie

    Bordeaux, 33076

    Not yet recruiting

  • Clinique Tivoli

    Bordeaux

    Not yet recruiting

  • Centre Francois Baclesse

    Caen, 14000

    Not yet recruiting

  • Centre Hospitalier de Carcassonne

    Carcassonne, 11000

    Not yet recruiting

  • Centre Hospitalier William Morey

    Chalon-sur-Saône

    Active, not recruiting

  • Centre Hospitalier Métropole de Savoie

    Chambéry, 73000

    Active, not recruiting

  • Centre d'Oncologie et de Radiothérapie 37

    Chambray-lès-Tours, 37170

    Not yet recruiting

  • CH Cholet

    Cholet, 49300

    Not yet recruiting

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

    Not yet recruiting

  • Hospices Civils de Colmar

    Colmar, 68000

    Active, not recruiting

  • Polyclinique Saint Côme

    Compiègne, 60200

    Not yet recruiting

  • Clinique de Flandre

    Coudekerque-Branche, 59210

    Not yet recruiting

  • Institut de Cancérologie de Bourgogne

    Dijon, 21000

    Not yet recruiting

  • CHI Fréjus St-Raphaël

    Fréjus

    Active, not recruiting

  • Polyclinique de Blois

    La Chaussée-Saint-Victor, 41260

    Not yet recruiting

  • Centre Hospitalier Départemental de Vendée

    La Roche-sur-Yon, 85925

    Not yet recruiting

  • CHU Grenoble

    La Tronche

    Not yet recruiting

  • Centre Hospitalier de Versailles

    Le Chesnay, 78150

    Not yet recruiting

  • Centre Hospitalier le Mans

    Le Mans, 72000

    Not yet recruiting

  • Clinique Victor Hugo

    Le Mans, 72000

    Not yet recruiting

  • Polyclinique de Limoges - Site Cinique Chénieux

    Limoges, 87039

    Not yet recruiting

  • Centre Hospitalier Universitaire de Limoges

    Limoges, 87042

    Active, not recruiting

  • Centre Leon Berard

    Lyon, 69008

    Recruiting

  • Hôpital Privé Jean Mermoz

    Lyon, 69008

    Active, not recruiting

  • Institut Paoli Calmettes

    Marseille

    Not yet recruiting

  • Institut Paoli Calmettes

    Marseille, Île-de-France Region, 13009

    Not yet recruiting

  • Centre Hospitalier Annecy Genevois

    Metz-Tessy

    Not yet recruiting

  • Centre de Cancerologie du Grand Montpellier

    Montpellier, 34070

    Recruiting

  • Groupe Hospitalier De La Region De Mulhouse Et Sud Alsace (GHRMSA)

    Mulhouse, 68100

    Recruiting

  • Hopital Privé du Confluent

    Nantes

    Not yet recruiting

  • Centre Antoine Lacassagne

    Nice, 06189

    Recruiting

  • CHU de NÎMES - Institut de Cancérologie du Gard

    Nîmes, 30029

    Not yet recruiting

  • CHU Orléans

    Orléans

    Active, not recruiting

  • Hopital Saint Louis

    Paris, 75010

    Not yet recruiting

  • Hopital Diaconesses-Croix Saint Simon

    Paris, 75020

    Active, not recruiting

  • Hôpital Tenon APHP

    Paris, 75020

    Not yet recruiting

  • Institut Curie

    Paris, Île-de-France Region, 75005

    Recruiting

  • Centre Hospitalier de Pau

    Pau, 64046

    Active, not recruiting

  • Hospices Civils de Lyon - Centre principal: Hôpital Lyon Sud

    Pierre-Bénite

    Not yet recruiting

  • CARIO - Centre Armoricain Radiothérapie Imagerie Médicale et Oncologie

    Plérin

    Active, not recruiting

  • CHU Poitiers

    Poitiers, 86180

    Not yet recruiting

  • Hôpital NOVO - Site PONTOISE

    Pontoise, 95300

    Not yet recruiting

  • Centre Hospitalier de Quimper

    Quimper, 29000

    Not yet recruiting

  • Clinique de la Croix du Sud

    Quint-Fonsegrives, 31130

    Not yet recruiting

  • Institut Jean Godinot

    Reims, 51100

    Recruiting

  • Centre Eugène Marquis

    Rennes, 35042

    Active, not recruiting

  • Centre Henri Becquerel

    Rouen

    Not yet recruiting

  • Institut Curie

    Saint-Cloud, 92219

    Recruiting

  • Hôpital Privé de la Loire

    Saint-Etienne, 42100

    Active, not recruiting

  • CHU de Saint Étienne

    Saint-Etienne, 42270

    Recruiting

  • Institut de Cancérologie de l'Ouest - Site René Gauducheau

    Saint-Herblain, 44800

    Not yet recruiting

  • Clinique Mutualiste de l'Estuaire

    Saint-Nazaire, 44600

    Active, not recruiting

  • Institut de Cancérologie Paris Nord - GCS RISSA

    Sarcelles, 95200

    Not yet recruiting

  • Groupe Hospitalier Rance Emeraude (GHRE)

    St-Malo, 35400

    Not yet recruiting

  • Centre Paul Stauss

    Strasbourg

    Active, not recruiting

  • Hôpitaux du Léman

    Thonon-les-Bains, 74200

    Active, not recruiting

  • Institut Claudius Regaud

    Toulouse, 31059

    Recruiting

  • CHU Bretonneau

    Tours, 37000

    Not yet recruiting

  • Centre Hospitalier de Valence

    Valence, 26000

    Not yet recruiting

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy

    Recruiting

  • Gustave Roussy

    Villejuif

    Active, not recruiting

Other trials in France

Germany28 sites, 28 recruiting

  • Universitätsklinikum Aachen AöR

    Aachen, 52074

    Not yet recruiting

  • Hämatologie-Onkologie im Zentrum MVZ GmbH

    Augsburg, 86150

    Not yet recruiting

  • GZW Hochwaldkrankenhaus

    Bad Nauheim, 61231

    Not yet recruiting

  • Praxisklinik Krebsheilkunde für Frauen / Brustzentrum

    Berlin, 10367

    Not yet recruiting

  • Helios Klinikum Berlin Buch

    Berlin, 13125

    Not yet recruiting

  • Hämato-Onklogische Praxis im Medicum

    Bremen, 28209

    Not yet recruiting

  • Medizinische Universität Lausitz - Carl-Thiem

    Cottbus, 03048

    Not yet recruiting

  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

    Dresden, 01307

    Not yet recruiting

  • Universitätsklinikum Düsseldorf AöR

    Düsseldorf, 40225

    Not yet recruiting

  • MVZ Medical Center Düsseldorf GmbH

    Düsseldorf, 40235

    Not yet recruiting

  • St.-Antonius-Hospital

    Eschweiler, 52249

    Not yet recruiting

  • Klinikum Esslingen GmbH

    Esslingen am Neckar, 73730

    Not yet recruiting

  • AGAPLESION Markus Krankenhaus

    Frankfurt, 60431

    Not yet recruiting

  • Evangelisches Klinikum Gelsenkirchen

    Gelsenkirchen, 45879

    Not yet recruiting

  • Mammazentrum HH am Krankenhaus Jerusalem

    Hamburg, 20357

    Not yet recruiting

  • Nationales Centrum für Tumorerkrankungen

    Heidelberg, 69120

    Not yet recruiting

  • Elisabeth Krankenhaus Kassel

    Kassel, 34117

    Not yet recruiting

  • InVO - Institut für Versorgungsforschung in der Onkologie

    Koblenz, 56068

    Not yet recruiting

  • Universitätsklinikum Leipzig

    Leipzig, 04103

    Not yet recruiting

  • Universitätsmedizin Mannheim

    Mannheim, 68167

    Not yet recruiting

  • St. Franziskus-Hospital Münster

    Münster, 48145

    Not yet recruiting

  • University Hospital Münster

    Münster, 48149

    Not yet recruiting

  • Sana Klinikum Offenbach

    Offenbach, 63069

    Not yet recruiting

  • MVZ für Hämatologie und Onkologie Ravensburg GmbH

    Ravensburg, 88212

    Not yet recruiting

  • University of Rostock

    Rostock, 18059

    Not yet recruiting

  • Universitätsklinikum Tübingen AöR

    Tübingen, 72076

    Not yet recruiting

  • Universitätsklinikum Ulm

    Ulm, 89075

    Not yet recruiting

  • Klinikum Worms gGmbH

    Worms, 67550

    Not yet recruiting

Other trials in Germany

Spain25 sites, 25 recruiting

  • Hospital Universitario de Badajoz

    Badajoz, 06006

    Recruiting

  • Hospital del Mar

    Barcelona, 08003

    Not yet recruiting

  • Hospital Vall d'Hebrón

    Barcelona, 08035

    Recruiting

  • Hospital Clínic de Barcelona

    Barcelona, 08036

    Recruiting

  • Hospital Universitario de Basurto

    Bilbao, 48013

    Not yet recruiting

  • Hospital Universitario de Fuenlabrada

    Fuenlabrada, 28942

    Not yet recruiting

  • Hospital Universitario Clínico San Cecilio

    Granada, 18016

    Recruiting

  • Hospital Universitario de Jaén

    Jaén, 23007

    Recruiting

  • Hospital Universitario de Jerez

    Jerez de la Frontera, 11405

    Recruiting

  • ICO Hospitalet

    L'Hospitalet de Llobregat, 08908

    Recruiting

  • Complejo Hospitalario Insular Materno-Infantil

    Las Palmas de Gran Canaria, 35016

    Recruiting

  • Hospital Severo Ochoa

    Leganés, 28911

    Not yet recruiting

  • Hospital Universitario Arnau de Vilanova de Lleida

    Lleida, 25198

    Recruiting

  • Hospital Universitario 12 Octubre

    Madrid, 28041

    Not yet recruiting

  • Hospital Materno-Infantil Málaga

    Málaga, 29011

    Recruiting

  • Hospital de Mataró

    Mataró, 08304

    Recruiting

  • Hospital Universitario Rey Juan Carlos

    Móstoles, 28933

    Not yet recruiting

  • Hospital Universitario Virgen de la Arrixaca

    Murcia, 30120

    Recruiting

  • Hospital Universitario Son Espases

    Palma de Mallorca, 07120

    Recruiting

  • Hospital Son Universitario Son Llatzer

    Palma de Mallorca, 07198

    Recruiting

  • Hospital Universitari Sant Joan de Reus

    Reus, 43204

    Recruiting

  • Hospital Universitari Parc Taulí

    Sabadell, 08208

    Recruiting

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39008

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

    Not yet recruiting

  • Hospital La Fe

    Valencia, 46026

    Recruiting

Other trials in Spain

Italy9 sites, 9 recruiting

  • IRCCS Centro di Riferimento Oncologico

    Aviano, 33081

    Not yet recruiting

  • AORN Sant'Anna e San Sebastiano

    Caserta, 81100

    Not yet recruiting

  • IRCCS Ospedale Policlinico San Martino - Università di Genova

    Genova, 16132

    Not yet recruiting

  • Azienda Ospedaliero-Universitaria Federico II

    Naples, 80131

    Not yet recruiting

  • IRCCS Istituto Nazionale dei Tumori Fondazione "G. Pascale"

    Naples, 80131

    Not yet recruiting

  • IRCCS Istituto Oncologico Veneto

    Padova, 32128

    Not yet recruiting

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56100

    Not yet recruiting

  • Ospedale F. Lotti Pontedera e Volterra, AUSL Toscana Nord Ovest

    Pontedera, 56125

    Not yet recruiting

  • IRCCS Fondazione Policlinico Universitaria "A. Gemelli"

    Roma, 00168

    Not yet recruiting

Other trials in Italy

Netherlands6 sites, 6 recruiting

  • Rijnstate Ziekenhuis Stichting

    Arnhem, 6815 AD

    Not yet recruiting

  • Tergooiziekenhuizen

    Hilversum, 1212 VG

    Not yet recruiting

  • Spaarne Gasthuis Stichting

    Hoofddorp, 2134 TM

    Not yet recruiting

  • Frisius MC

    Leeuwarden, 8934 AD

    Not yet recruiting

  • Leids Universitair Medisch Centrum (LUMC)

    Leiden, 2333 ZA

    Not yet recruiting

  • Stichting Viecuri Medisch Centrum voor Noord-Limburg

    Venlo, 5912 BL

    Not yet recruiting

Other trials in Netherlands

About this study

Official title: No Chemotherapy in Intermediate-risk HR+ HER2- Early Breast Cancer Treated With Ribociclib (LEE-011) in the Adjuvant Setting, a Non-inferiority Phase III Trial

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.

Read the detailed description

The advent of CDK4/6 inhibitors has changed the outlook of patients with metastatic hormone receptor-positive (HR+) HER2- breast cancer. Moreover, including CDK4/6 inhibitors in the adjuvant treatment regimens strategies has led to significant gains in disease-free survival.

The phase III NATALEE trial demonstrated the efficacy of an adjuvant three-year treatment with ribociclib in prolonging invasive disease-free survival (iDFS) in patients with intermediate and high-risk HR+ HER2- early breast cancer.

Contrarily to similar studies of CDK4/6 inhibitors in this setting, NATALEE included a group of patients with intermediate clinical risk (pT1-2 pN1, pT3-4 pN0 or pT2 pN0 with histological grade 3 or grade 2 with Ki67≥ 20%). These patients are usually considered for adjuvant chemotherapy based on their clinicopathological conditions or the results of a genomic signature (e.g. Oncotype Dx). Nevertheless, the benefit of adjuvant chemotherapy in these patients is uncertain (and likely small) in the context of an adjuvant treatment strategy that includes a CDK 4/6 inhibitor.

As such, a de-escalation trial could demonstrate that patients with intermediate-risk breast cancer treated with CDK4/6 inhibitors could be spared the dreaded chemotherapy side effects while ensuring similar survival outcomes.

In order to be generalizable and practice changing, a trial in this setting should aim to be as pragmatic as possible, particularly in inclusion criteria, with the required resources for patient inclusion and delivery of care being as similar as possible to those employed in usual care. As such, chemotherapy eligibility should be defined similarly to routine clinical practice in the participating centers (i.e. using routine clinicopathological parameters and/or genomic signatures).

While single-arm designs could help address non-inferiority in the previously mentioned setting, they are usually compared to historical controls and lack external validation. Moreover, in some settings, like early breast cancer, the standard of care may change relatively quickly (e.g. Oncotype Dx-based chemotherapy de-escalation or adjuvant CDK4/6 inhibitors use), rendering the comparison to historical controls challenging, limiting the study conclusions and their impact on clinical practice. Finally, there is no consensus on the optimal non-inferiority threshold in single-arm trials using historical controls as a comparator. As such, randomized controlled non-inferiority trials with a strict non-inferiority margin remain the gold standard design to prove that a de-escalated treatment regimen is safe and advantageous, and the only ones capable of producing level IA evidence according to ESMO (Trapani et al., Annals of Oncology 2022).

Conditions
Breast Cancer
Being tested
Chemotherapy followed by endocrine therapy and ribociclib treatment, De-escalation
Keywords
De-escalation, Chemotherapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chemotherapy followed by endocrine therapy and ribociclib treatmentDrug

    Also called Ribociclib, Adjuvant hormonotherapy

    Endocrine therapy and ribociclib treatment

  • De-escalationOther

    Also called Ribociclib, Adjuvant hormonotherapy

    De-escalation of the chemotherapy in the adjuvant setting

Study groups in NCT07237256
Study groupRoleWhat they receive
Investigational arm (Arm A)ExperimentalRibociclib and endocrine therapy (ET)
Receives: Other: De-escalation
Control arm (Arm B)OtherChemotherapy followed by ribociclib and endocrine therapy
Receives: Drug: Chemotherapy followed by endocrine therapy and ribociclib treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Invasive breast cancer-free survival (iBCFS)

    iBCFS is defined as the time from the date of randomization to the date of the first event of invasive ipsilateral breast tumor recurrence, local-regional invasive recurrence, distant recurrence, death (any cause) or invasive contralateral breast cancer as assessed by investigator.

    Measured: From ramdomization to iBCFS, up to 12 years.

Secondary outcomes (7)

  1. Invasive disease-free survival (iDFS)

    iDFS is defined as the time from date of randomization to the date of the first iDFS event that is: i) same event as IBCFS, or ii) secondary invasive non breast cancer.

    Measured: From ramdomization to iDFS event, up to 12 years.

  2. Distance disease-free survival (DDFS)

    DDFS is defined as the time from the date of randomization to the date of the first event of distant recurrence, death (any cause), or second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin).

    Measured: From ramdomization to DDFS event, up to 12 years.

  3. Overall survival (OS)

    OS is defined as the time from the date of randomization to the date of death due to any cause

    Measured: From ramdomization to death from any cause, up to 12 years.

  4. Type of iBCFS event

    To evaluate the rate of the different types of iBCFS events in each treatment arm

    Measured: From ramdomization to iBCFS event, up to 12 years.

  5. Acute and late toxicity during the study focusing on grade ≥2

    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3

    = "severe", 4 = "life-threatening", and 5 = "death")

    Measured: Throughout study completion, up to 8.5 years.

  6. Quality of life questionnaire - Core 30 (QLQ-C30)

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: At baseline, 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, 8.5 years from randomization.

  7. Quality of Life Questionnaire - Breast cancer module (QLQ-BR42)

    This EORTC breast cancer specific questionnaire is intended to supplement the QLQ-C30.

    The QLQ-BR42 incorporates nine multi-item scales to assess body image, sexual functioning, breast satisfaction, systemic therapy side effects, arm symptoms, breast symptoms, endocrine therapy symptoms, skin mucosis symptoms, endocrine sexual symptoms. In addition, single items assess sexual enjoyment, future perspective and being upset by hair loss. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. Higher scores indicate more severe symptoms or problems for all items.

    Measured: At baseline, 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, 8.5 years from randomization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2025
  2. Study start18 Dec 2025
  3. Primary completion30 Nov 2033 (estimated)
  4. Study completion31 Dec 2037 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
* Investigational arm (Arm A): ribociclib and endocrine therapy (ET) * Control arm (Arm B): chemotherapy followed by ribociclib and endocrine therapy
Masking
None (open label)
Enrolment
3,902 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07237256
Sponsor's protocol ID
UC-BCG-2501
Other IDs
2025-520979-13-00, 2025
Acronym
NoLEEta
Status last verified
Mar 2026
First submitted
14 Nov 2025
Last updated
26 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Chemotherapy followed by endocrine therapy and ribociclib treatment and De-escalation in people with Breast Cancer, run by UNICANCER at 138 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 138 sites in France, Germany, Spain, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sandrine Marques (+33 (0) 6 17 90 00 54, s-marques@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Invasive breast cancer-free survival (iBCFS) (time frame: From ramdomization to iBCFS, up to 12 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07237256.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.

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