Neoadjuvant and Adjuvant Ribociclib and ET for Clinically High-risk ER+ and HER2- Breast Cancer

NCT05296746 | Recruiting Phase 2 DMC

• 2 other identifiers: SOLTI-1911BIG-21-02
• Study Type: interventional
• Target: 1,100
• Locations: 3 countries
• Sites: 51

Brief Summary

This is an open-label, multicenter international trial in men and women with primary operable HR+/HER2-, ki67≥20%, grade 2 or 3 and stage II breast cancer to evaluate safety and long-term efficacy of a non-chemo treatment in patients biologically responders to neoadjuvant ribociclib and letrozole. This study aims to evaluate whether chemotherapy could be avoided for initial high-risk clinicopathological breast cancer patients that are converted to low genomic risk assessed by Risk of Recurrence-low (ROR-low) at 6 months of letrozole - ribociclib neoadjuvant treatment by continuing with this treatment in adjuvant setting.

Conditions

Breast Cancer Stage II

Keywords

breast cancer; ribociclib; ROR score; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Distant metastasis-free survival (DMFS) in the ROR-low cohort (responder cohort)

  DMFS is defined as the time from date of surgery to date of first event of distant metastatic recurrence or death (any cause).

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

Secondary Outcomes (6)

• Invasive disease-free survival (IDFS) in the ROR-low cohort (responder cohort)

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

• Pathological complete response in breast and axillary lymph nodes (pCRBL)

  At surgery (after 6 months of neoadjuvant treatment)

• Residual Cancer Burden 0/1 (RCB0/1)

  At surgery (after 6 months of neoadjuvant treatment)

• Rate of ROR-low (at surgery) after neoadjuvant treatment.

  At surgery (after 6 months of neoadjuvant treatment)

• Distant metastasis-free survival (DMFS) in the ROR-medium/high cohort (non-responder cohort)

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

Other Outcomes (7)

• Correlation between DMFS and pCR

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

• Correlation between DMFS and ROR score (as a continuous variable)

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

• Correlation between DMFS and RCB

  Until recurrence (if it happens) for a maximum of 7.5 years of follow-up

Study Arms (2)

Responder (ROR-low)

EXPERIMENTAL

Ribociclib (400 mg/day; 3 weeks ON and 1 week OFF) in the adjuvant setting for 33 cycles. Letrozole or other aromatase inhibitor treatment duration must be of at least 5 years

Drug: Ribociclib (neoadjuvant); Drug: Ribociclib (adjuvant)

Non-responder (ROR-medium/high)

OTHER

Adjuvant chemotherapy. 3 regimens are permitted. Regimen 1: \- Doxorubicin 60 mg/m2 IV day 1 (or Epirubicin 75-100 mg/m2) and Cyclophosphamide 600-830 mg/m2 day 1 every 14/21 days for 4 cycles, followed by Paclitaxel 80 mg/m2 every week for 12 weeks or Docetaxel 75-100 mg/m2 every 3 weeks for 12 weeks. Regimen 2: \- Docetaxel 75-100 mg/m2 IV day 1 and Cyclophosphamide 600-830 mg/m2 day 1 every 21 days for 4-6 cycles. Regimen 3: \- Paclitaxel 80 mg/m2 every week for 12 weeks or Docetaxel 75-100 mg/m2 every 3 weeks for 12 weeks followed by Doxorubicin 60 mg/m2 IV day 1 (or Epirubicin 75-100 mg/m2) and Cyclophosphamide 600-830 mg/m2 day 1 every 14/21 days for 4 cycles. Then, patients will receive ribociclib (400 mg/day; 3 weeks ON and 1 week OFF) in the adjuvant setting for 33 cycles. Letrozole or other aromatase inhibitor treatment duration must be of at least 5 years

Drug: Ribociclib (neoadjuvant); Drug: Chemotherapy (adjuvant); Drug: Ribociclib (adjuvant)

Interventions

Ribociclib (neoadjuvant) DRUG

Ribociclib 600 mg/day + letrozole during neoadjuvant phase.

Also known as: Kisqali

Non-responder (ROR-medium/high); Responder (ROR-low)

Chemotherapy (adjuvant) DRUG

Adjuvant chemotherapy. 3 regimens are permitted.

Non-responder (ROR-medium/high)

Ribociclib (adjuvant) DRUG

Ribociclib 400 mg/day + letrozole (or other aromatase inhibitor) during adjuvant phase.

Also known as: Kisqali

Non-responder (ROR-medium/high); Responder (ROR-low)

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form prior to any study-specific procedure. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
• Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent)
• Male (≥18 years old) or pre-menopausal women (≥40 years old) or post-menopausal women. Premenopausal/male patients will receive LHRH agonists 2 weeks before C1D1 and during treatment. Post-menopausal status is defined as:
• Age ≥60 years or
• Age \<60 years and 12 months of amenorrhea plus follicle stimulating hormone (FSH) and plasma estradiol (E2) levels within post-menopausal range by local laboratory assessment or
• Prior bilateral oophorectomy (≥7 days prior to Day 1 of treatment).
• Histologically confirmed invasive breast carcinoma, confirmed by the local pathologist, with all the following characteristics:
• Clinical stage II (Seventh Edition of the AJCC) which includes cT1cN1cM0, cT2cN0cM0, cT2cN1cM0 and cT3cN0cM0.
• ER-positive/HER2-negative according to the most recent ASCO/CAP guidelines assessed locally, tumor cells \>10% ER staining, grade 2 or 3 breast cancer.
• Ki-67 index by local analysis of ≥20% on untreated tumor tissue and/or high genomic risk (defined by gene signature): Oncotype DX® RS ≥ 26, Mammaprint® = Risk of Recurrence High, Prosigna® ROR ≥ 60 or luminal B, or Endopredict® = Risk of Recurrence High.
• Note: Multifocal and multicentric tumors are permitted if they are considered clinical stage II according to Seventh Edition of the AJCC. Biopsy of all lesions is not necessary.
• Breast cancer eligible for primary surgery.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the date of enrolment.
• Adequate hematological, renal and hepatic function, as follows:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L

You may not qualify if:

• Any prior treatment for primary invasive breast cancer. Letrozole or other drugs used during the preservation of ovarian function are permitted if administered after baseline biopsy.
• Inoperable breast cancer.
• Patients with Stage I, III or IV breast cancer are not eligible. Baseline staging to document absence of metastatic disease is not required, however is recommended as determined by institutional practice (in patients where there may be a reasonable suspicion of advanced disease e.g., large tumors, clinically positive axillary lymph nodes, signs and symptoms). If performed, reports of these examinations must be available. Examination type for staging, i.e. X-ray, sonography, bone scan, CT, MRI, and/or PET-CT, is at the discretion of the investigator.
• Bilateral invasive breast cancer.
• Patients who have undergone sentinel lymph node biopsy prior to study treatment.
• Inability or unwillingness to swallow pills.
• Malabsorption syndrome or other condition that would interfere with enteric absorption of study drugs.
• Participation in a prior investigational study within 30 days prior to enrolment or within 5 half-lives of the investigational product, whichever is longer.
• Patient with a Child-Pugh score B or C.
• Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 12 months prior to screening.
• History of documented congestive heart failure (New York Heart Association functional classification III-IV).
• Documented cardiomyopathy.
• Patient has a Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block).

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Novartis: collaborator
• UNICANCER: collaborator

Study Sites (51)

Sainte Catherine - Institut du Cancer Avignon Provence

Avignon, France

RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, France

RECRUITING

Centre Hospitalier Universitaire de Besancon

Besançon, France

RECRUITING

Hôpital Simone veil de Blois

Blois, France

RECRUITING

Centre François Baclesse

Caen, France

RECRUITING

Centre Hospitalier de Cholet

Cholet, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Hospitalier Universitaire de Grenoble Alpes

Grenoble, France

RECRUITING

Hôpital Franco Britanique Fondation Cognacq Jay

Levallois-Perret, France

RECRUITING

Centre Oscar lambret

Lille, France

RECRUITING

Centre Hospitalier Universitaire de Limoges

Limoges, France

RECRUITING

Centre Léon Berard

Lyon, France

RECRUITING

Hôpital privé Jean Mermoz

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

Hôpital privé de Confluent

Nantes, France

RECRUITING

Institut Curie

Paris, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, France

RECRUITING

Centre Hospitalier les Cornouaille

Quimper, France

RECRUITING

Institut Jean Godinot

Reims, France

RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

Institut Curie

Saint-Cloud, France

RECRUITING

Centre Hospitalier Privé Saint-Grégoire

Saint-Grégoire, France

RECRUITING

Clinique Mutualiste de l'Estuaire - Groupe HGO

Saint-Nazaire, France

RECRUITING

Clinique Sainte Anne - Strasbourg Oncologie Libérale

Strasbourg, France

RECRUITING

Institut de cancérologie Strasbourg Europe - ICANS

Strasbourg, France

RECRUITING

Hopitaux du Léman

Thonon-les-Bains, France

RECRUITING

Clinique Pasteur

Toulouse, France

RECRUITING

Institut Claudius Regaud, IUCT-Oncopole

Toulouse, France

RECRUITING

Nouvelle Clinique des Dentellières

Valenciennes, France

RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

RECRUITING

Centre Hospitalier Bretagne Atlantique

Vannes, France

RECRUITING

Gustave Roussy

Villejuif, France

RECRUITING

Hospital da Luz

Lisbon, Portugal

SUSPENDED

Hospital de São Francisco Xavier

Lisbon, Portugal

SUSPENDED

IPO Porto

Porto, Portugal

SUSPENDED

Hospital Son Espases

Palma de Mallorca, Balearic Islands, Spain

RECRUITING

ICO Badalona

Badalona, Barcelona, Spain

RECRUITING

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Spain

RECRUITING

Hospital Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital Universiatrio Clínico San Cecilio

Granada, Spain

RECRUITING

Complejo Asistencial Universitario de León

León, Spain

RECRUITING

Fundación Jiménez Díaz

Madrid, Spain

RECRUITING

HM Sanchinarro

Madrid, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Ramón y Cajal

Madrid, Spain

RECRUITING

Complejo Asistencial Universitario de Salamanca

Salamanca, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Spain

RECRUITING

Hospital Clínico de Valencia

Valencia, Spain

RECRUITING

Instituto Valenciano de Oncología

Valencia, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Neoadjuvant Therapy; Chemotherapy, Adjuvant; Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Aleix Prat, MD

  Hospital Clínic de Barcelona/SOLTI

  PRINCIPAL INVESTIGATOR

• Paul Cottu, MD

  Institut Curie Paris

  PRINCIPAL INVESTIGATOR

• Joaquín Gavilá, MD

  Instituto Valenciano de Oncología

  PRINCIPAL INVESTIGATOR

• Thibault de La Motte Rouge, MD

  Centre Eugène Marquis, Rennes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

InfoSOLTI

CONTACT

93 343 63 02; info@gruposolti.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: March 25, 2022
• Study Start: May 3, 2022
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 18, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3); ES (15); FR (33)