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

NCT07237256 | Recruiting Phase 3 DMC

• 2 other identifiers: UC-BCG-25012025-520979-13-00
• Study Type: interventional
• Target: 3,902
• Locations: 5 countries
• Sites: 138

Brief 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-). 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.

Conditions

Breast Cancer

Keywords

De-escalation; Chemotherapy

Outcome Measures

Primary Outcomes (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.

  From ramdomization to iBCFS, up to 12 years.

Secondary Outcomes (7)

• Invasive disease-free survival (iDFS)

  From ramdomization to iDFS event, up to 12 years.

• Distance disease-free survival (DDFS)

  From ramdomization to DDFS event, up to 12 years.

• Overall survival (OS)

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

• Type of iBCFS event

  From ramdomization to iBCFS event, up to 12 years.

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

  Throughout study completion, up to 8.5 years.

Study Arms (2)

Investigational arm (Arm A)

EXPERIMENTAL

Ribociclib and endocrine therapy (ET)

Other: De-escalation

Control arm (Arm B)

OTHER

Chemotherapy followed by ribociclib and endocrine therapy

Drug: Chemotherapy followed by endocrine therapy and ribociclib treatment

Interventions

De-escalation OTHER

De-escalation of the chemotherapy in the adjuvant setting

Also known as: Ribociclib, Adjuvant hormonotherapy

Investigational arm (Arm A)

Chemotherapy followed by endocrine therapy and ribociclib treatment DRUG

Endocrine therapy and ribociclib treatment

Also known as: Ribociclib, Adjuvant hormonotherapy

Control arm (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: collaborator
• Gruppo Italiano Mammella (GIM): collaborator
• BOOG Study Center: collaborator
• Canadian Cancer Trials Group: collaborator
• UNICANCER: lead
• Novartis: collaborator
• GBG Forschungs GmbH: collaborator
• Latin American Cooperative Oncology Group: collaborator
• Swiss Cancer Institute: collaborator
• Menarini Silicon Biosystems, INC: collaborator

Study Sites (138)

Clinique de l'Europe

Amiens, 80090, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest - Site Paul Papin

Angers, 49055, France

NOT YET RECRUITING

CH Victor Dupouy

Argenteuil, 95107, France

NOT YET RECRUITING

CH Henri Mondor

Aurillac, 15000, France

ACTIVE NOT RECRUITING

Centre Hospitalier d'Auxerre

Auxerre, France

NOT YET RECRUITING

Sainte Catherine - Institut du Cancer Avignon Provence

Avignon, 84918, France

RECRUITING

Centre Hospitalier de la Cote Basque

Bayonne, 64100, France

ACTIVE NOT RECRUITING

Centre Hospitalier Simone Veil de Beauvais

Beauvais, 60021, France

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire de Besancon

Besançon, 25000, France

NOT YET RECRUITING

Institut Bergonie

Bordeaux, 33076, France

NOT YET RECRUITING

Clinique Tivoli

Bordeaux, France

NOT YET RECRUITING

Centre Francois Baclesse

Caen, 14000, France

NOT YET RECRUITING

Centre Hospitalier de Carcassonne

Carcassonne, 11000, France

NOT YET RECRUITING

Centre Hospitalier William Morey

Chalon-sur-Saône, France

ACTIVE NOT RECRUITING

Centre Hospitalier Métropole de Savoie

Chambéry, 73000, France

ACTIVE NOT RECRUITING

Centre d'Oncologie et de Radiothérapie 37

Chambray-lès-Tours, 37170, France

NOT YET RECRUITING

CH Cholet

Cholet, 49300, France

NOT YET RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

NOT YET RECRUITING

Hospices Civils de Colmar

Colmar, 68000, France

ACTIVE NOT RECRUITING

Polyclinique Saint Côme

Compiègne, 60200, France

NOT YET RECRUITING

Clinique de Flandre

Coudekerque-Branche, 59210, France

NOT YET RECRUITING

Institut de Cancérologie de Bourgogne

Dijon, 21000, France

NOT YET RECRUITING

CHI Fréjus St-Raphaël

Fréjus, France

ACTIVE NOT RECRUITING

Polyclinique de Blois

La Chaussée-Saint-Victor, 41260, France

NOT YET RECRUITING

Centre Hospitalier Départemental de Vendée

La Roche-sur-Yon, 85925, France

NOT YET RECRUITING

CHU Grenoble

La Tronche, France

NOT YET RECRUITING

Centre Hospitalier de Versailles

Le Chesnay, 78150, France

NOT YET RECRUITING

Centre Hospitalier le Mans

Le Mans, 72000, France

NOT YET RECRUITING

Clinique Victor Hugo

Le Mans, 72000, France

NOT YET RECRUITING

Polyclinique de Limoges - Site Cinique Chénieux

Limoges, 87039, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Limoges

Limoges, 87042, France

ACTIVE NOT RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Hôpital Privé Jean Mermoz

Lyon, 69008, France

ACTIVE NOT RECRUITING

Institut Paoli Calmettes

Marseille, France

NOT YET RECRUITING

Centre Hospitalier Annecy Genevois

Metz-Tessy, France

NOT YET RECRUITING

Centre de Cancerologie du Grand Montpellier

Montpellier, 34070, France

RECRUITING

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

Mulhouse, 68100, France

RECRUITING

Hopital Privé du Confluent

Nantes, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

CHU de NÎMES - Institut de Cancérologie du Gard

Nîmes, 30029, France

NOT YET RECRUITING

CHU Orléans

Orléans, France

ACTIVE NOT RECRUITING

Hopital Saint Louis

Paris, 75010, France

NOT YET RECRUITING

Hopital Diaconesses-Croix Saint Simon

Paris, 75020, France

ACTIVE NOT RECRUITING

Hôpital Tenon APHP

Paris, 75020, France

NOT YET RECRUITING

Centre Hospitalier de Pau

Pau, 64046, France

ACTIVE NOT RECRUITING

Hospices Civils de Lyon - Centre principal: Hôpital Lyon Sud

Pierre-Bénite, France

NOT YET RECRUITING

CARIO - Centre Armoricain Radiothérapie Imagerie Médicale et Oncologie

Plérin, France

ACTIVE NOT RECRUITING

CHU Poitiers

Poitiers, 86180, France

NOT YET RECRUITING

Hôpital NOVO - Site PONTOISE

Pontoise, 95300, France

NOT YET RECRUITING

Centre Hospitalier de Quimper

Quimper, 29000, France

NOT YET RECRUITING

Clinique de la Croix du Sud

Quint-Fonsegrives, 31130, France

NOT YET RECRUITING

Institut Jean Godinot

Reims, 51100, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

ACTIVE NOT RECRUITING

Centre Henri Becquerel

Rouen, France

NOT YET RECRUITING

Institut Curie

Saint-Cloud, 92219, France

RECRUITING

Hôpital Privé de la Loire

Saint-Etienne, 42100, France

ACTIVE NOT RECRUITING

CHU de Saint Étienne

Saint-Etienne, 42270, France

RECRUITING

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, 44800, France

NOT YET RECRUITING

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, 44600, France

ACTIVE NOT RECRUITING

Institut de Cancérologie Paris Nord - GCS RISSA

Sarcelles, 95200, France

NOT YET RECRUITING

Groupe Hospitalier Rance Emeraude (GHRE)

St-Malo, 35400, France

NOT YET RECRUITING

Centre Paul Stauss

Strasbourg, France

ACTIVE NOT RECRUITING

Hôpitaux du Léman

Thonon-les-Bains, 74200, France

ACTIVE NOT RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

CHU Bretonneau

Tours, 37000, France

NOT YET RECRUITING

Centre Hospitalier de Valence

Valence, 26000, France

NOT YET RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

RECRUITING

Gustave Roussy

Villejuif, France

ACTIVE NOT RECRUITING

Institut Paoli Calmettes

Marseille, Île-de-France Region, 13009, France

NOT YET RECRUITING

Institut Curie

Paris, Île-de-France Region, 75005, France

RECRUITING

Universitätsklinikum Aachen AöR

Aachen, 52074, Germany

NOT YET RECRUITING

Hämatologie-Onkologie im Zentrum MVZ GmbH

Augsburg, 86150, Germany

NOT YET RECRUITING

GZW Hochwaldkrankenhaus

Bad Nauheim, 61231, Germany

NOT YET RECRUITING

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum

Berlin, 10367, Germany

NOT YET RECRUITING

Helios Klinikum Berlin Buch

Berlin, 13125, Germany

NOT YET RECRUITING

Hämato-Onklogische Praxis im Medicum

Bremen, 28209, Germany

NOT YET RECRUITING

Medizinische Universität Lausitz - Carl-Thiem

Cottbus, 03048, Germany

NOT YET RECRUITING

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

NOT YET RECRUITING

Universitätsklinikum Düsseldorf AöR

Düsseldorf, 40225, Germany

NOT YET RECRUITING

MVZ Medical Center Düsseldorf GmbH

Düsseldorf, 40235, Germany

NOT YET RECRUITING

St.-Antonius-Hospital

Eschweiler, 52249, Germany

NOT YET RECRUITING

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

NOT YET RECRUITING

AGAPLESION Markus Krankenhaus

Frankfurt, 60431, Germany

NOT YET RECRUITING

Evangelisches Klinikum Gelsenkirchen

Gelsenkirchen, 45879, Germany

NOT YET RECRUITING

Mammazentrum HH am Krankenhaus Jerusalem

Hamburg, 20357, Germany

NOT YET RECRUITING

Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

NOT YET RECRUITING

Elisabeth Krankenhaus Kassel

Kassel, 34117, Germany

NOT YET RECRUITING

InVO - Institut für Versorgungsforschung in der Onkologie

Koblenz, 56068, Germany

NOT YET RECRUITING

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

NOT YET RECRUITING

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

NOT YET RECRUITING

St. Franziskus-Hospital Münster

Münster, 48145, Germany

NOT YET RECRUITING

University Hospital Münster

Münster, 48149, Germany

NOT YET RECRUITING

Sana Klinikum Offenbach

Offenbach, 63069, Germany

NOT YET RECRUITING

MVZ für Hämatologie und Onkologie Ravensburg GmbH

Ravensburg, 88212, Germany

NOT YET RECRUITING

University of Rostock

Rostock, 18059, Germany

NOT YET RECRUITING

Universitätsklinikum Tübingen AöR

Tübingen, 72076, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, 89075, Germany

NOT YET RECRUITING

Klinikum Worms gGmbH

Worms, 67550, Germany

NOT YET RECRUITING

IRCCS Centro di Riferimento Oncologico

Aviano, 33081, Italy

NOT YET RECRUITING

AORN Sant'Anna e San Sebastiano

Caserta, 81100, Italy

NOT YET RECRUITING

IRCCS Ospedale Policlinico San Martino - Università di Genova

Genova, 16132, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Federico II

Naples, 80131, Italy

NOT YET RECRUITING

IRCCS Istituto Nazionale dei Tumori Fondazione "G. Pascale"

Naples, 80131, Italy

NOT YET RECRUITING

IRCCS Istituto Oncologico Veneto

Padova, 32128, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, 56100, Italy

NOT YET RECRUITING

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

Pontedera, 56125, Italy

NOT YET RECRUITING

IRCCS Fondazione Policlinico Universitaria "A. Gemelli"

Roma, 00168, Italy

NOT YET RECRUITING

Rijnstate Ziekenhuis Stichting

Arnhem, 6815 AD, Netherlands

NOT YET RECRUITING

Tergooiziekenhuizen

Hilversum, 1212 VG, Netherlands

NOT YET RECRUITING

Spaarne Gasthuis Stichting

Hoofddorp, 2134 TM, Netherlands

NOT YET RECRUITING

Frisius MC

Leeuwarden, 8934 AD, Netherlands

NOT YET RECRUITING

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

NOT YET RECRUITING

Stichting Viecuri Medisch Centrum voor Noord-Limburg

Venlo, 5912 BL, Netherlands

NOT YET RECRUITING

Hospital Universitario de Badajoz

Badajoz, 06006, Spain

RECRUITING

Hospital del Mar

Barcelona, 08003, Spain

NOT YET RECRUITING

Hospital Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Universitario de Basurto

Bilbao, 48013, Spain

NOT YET RECRUITING

Hospital Universitario de Fuenlabrada

Fuenlabrada, 28942, Spain

NOT YET RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, 18016, Spain

RECRUITING

Hospital Universitario de Jaén

Jaén, 23007, Spain

RECRUITING

Hospital Universitario de Jerez

Jerez de la Frontera, 11405, Spain

RECRUITING

ICO Hospitalet

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Complejo Hospitalario Insular Materno-Infantil

Las Palmas de Gran Canaria, 35016, Spain

RECRUITING

Hospital Severo Ochoa

Leganés, 28911, Spain

NOT YET RECRUITING

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, 25198, Spain

RECRUITING

Hospital Universitario 12 Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Hospital de Mataró

Mataró, 08304, Spain

RECRUITING

Hospital Materno-Infantil Málaga

Málaga, 29011, Spain

RECRUITING

Hospital Universitario Rey Juan Carlos

Móstoles, 28933, Spain

NOT YET RECRUITING

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

RECRUITING

Hospital Universitario Son Espases

Palma de Mallorca, 07120, Spain

RECRUITING

Hospital Son Universitario Son Llatzer

Palma de Mallorca, 07198, Spain

RECRUITING

Hospital Universitari Sant Joan de Reus

Reus, 43204, Spain

RECRUITING

Hospital Universitari Parc Taulí

Sabadell, 08208, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

NOT YET RECRUITING

Hospital La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• François-Clément BIDARD, PhD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandrine Marques

CONTACT

+33 (0) 6 17 90 00 54; s-marques@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * Investigational arm (Arm A): ribociclib and endocrine therapy (ET) * Control arm (Arm B): chemotherapy followed by ribociclib and endocrine therapy

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 19, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): November 30, 2033
• Study Completion (Estimated): December 31, 2037
• Last Updated: May 26, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (70); NL (6); IT (9); DE (28); ES (25)