Neoadjuvant Study Chemotherapy vs Letrozole + Abemaciclib in HR+/HER2- High/Intermediate Risk Breast Cancer Patients

NCT04293393 | Active Not Recruiting Phase 2 Results

• 2 other identifiers: GEICAM/2019-012019-002123-15
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 28

Brief Summary

Phase II, randomized, open-label, international, multicenter study to compare efficacy of standard chemotherapy vs. letrozole plus abemaciclib as neoadjuvant therapy in HR-positive/HER2-negative high/intermediate risk breast cancer patients

Conditions

Early Breast Cancer

Keywords

Abemaciclib; Neoadjuvant; HR positive; HER2 negative; High/intermediate risk

Outcome Measures

Primary Outcomes (1)

• Residual Cancer Burden (RCB) 0-I Rate

  Evaluation of the number of patients with a RCB 0-I index as a measure of efficacy. RCB is a continuous variable derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. It is estimated from routine pathological sections of the primary breast tumor site and the regional lymph nodes after the completion of Neoadjuvant therapy. The pathological variables include bidimensional diameters of the primary tumor bed, the proportion of primary tumor area containing invasive carcinoma, the number of positive lymph nodes, and the diameter of the largest nodal metastasis

  Through study treatment, and average of 12 months

Secondary Outcomes (8)

• Changes in Percentage of KI67 Dyed Cells

  2 weeks of treatment

• RCB 0+I Versus RCB-II Versus RCB-III

  24 weeks

• Number of Participants With Preoperative Endocrine Prognostic Index (PEPI) Score of 0 at Surgery

  24 weeks

• Clinical Response Measured by Magnetic Resonance Imaging (MRI)

  24 weeks

• Rate of Breast Conservative Surgery (BCS) in Both Treatment Arms.

  24 weeks

Study Arms (2)

Arm A: Doxorubicin plus cyclophosphamide and taxane

ACTIVE COMPARATOR

Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles. Approximately duration of 24 weeks (6 months).

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Taxane

Arm B: Letrozole plus abemaciclib +/- LHRH

EXPERIMENTAL

Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- luteinizing hormone-releasing hormone (LHRH) analogs in premenopausal women, up to 12 months, in 28-day cycles.

Drug: Letrozole; Drug: Abemaciclib; Drug: LHRH Analogue

Interventions

Doxorubicin DRUG

Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.

Also known as: Caelyx

Arm A: Doxorubicin plus cyclophosphamide and taxane

Cyclophosphamide DRUG

Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.

Also known as: Genoxal

Arm A: Doxorubicin plus cyclophosphamide and taxane

Taxane DRUG

Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.

Also known as: Paclitaxel, Docetaxel

Arm A: Doxorubicin plus cyclophosphamide and taxane

Letrozole DRUG

Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles

Also known as: Femara

Arm B: Letrozole plus abemaciclib +/- LHRH

Abemaciclib DRUG

Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles

Also known as: Verzenios

Arm B: Letrozole plus abemaciclib +/- LHRH

LHRH Analogue DRUG

Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles

Also known as: Goserelin, Leuprolide

Arm B: Letrozole plus abemaciclib +/- LHRH

Eligibility Criteria

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

You may qualify if:

• Patients are eligible to be enrolled in the study only if they meet all of the following criteria:
• Written informed consent prior to any specific study procedures.
• Women ≥ 18 years of age.
• Documentation of histologically confirmed primary invasive adenocarcinoma of the breast.
• Availability of a primary tumor tissue sample obtained during the diagnostic process before treatment for the central assessment of Ki67 index.
• Documentation of Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor 2 (HER2) negative Breast Cancer (BC) based on local laboratory determination.
• HR positive is defined as more than or equal to 10% positive cells by Immunohistochemistry (IHC) for ER and/or progesterone receptor (PgR).
• HER2 negative tumor is determined according to recommendations of American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guidelines.
• Intermediate and high risk patients based on Ki67 index value (≥ 20%) determined at a central laboratory.
• Patients should be in the following clinical stages of disease according to the 8th edition of the TNM Classification of Breast Cancer by the Union for International Cancer Control (UICC): T2 (\> 2cm) - T3, T4b, N0 - N2, M0 (stages IIA, IIB, IIIA or IIIB). Subpopulation with tumors T2 N0 M0 will include high risk patients based on Ki67 index \> 30% or Ki67 index between 20-30% and PgR negative with or without histological grade 3.
• Indication of neoadjuvant treatment.
• At the time of presentation, patients must be candidates for potentially curative surgery by surgeon's assessment.
• Sentinel lymph node biopsy (SLNB) will be preferable after the neoadjuvant treatment. Those patients with SLNB before the neoadjuvant treatment will be eligible for the study only if the SLNB has a negative result (N0). One Step Nucleic Acid Amplification (OSNA) method is not allowed.
• Premenopausal and postmenopausal women. Postmenopausal status is defined as:
• Patient underwent bilateral oophorectomy, or

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Previous anti-cancer treatment with therapeutic intent for current breast cancer is not allowed.
• Inflammatory breast cancer, multifocal/multicentric breast cancer with ≥ 3 tumor lesions or synchronous bilateral invasive breast cancers are not eligible.
• Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \< 30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption.
• Females who are pregnant or lactating.
• Active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or colorectal.
• Prior hematopoietic stem cell or bone marrow transplantation.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Eli Lilly and Company: collaborator

Study Sites (28)

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, A Coruña, 15706, Spain

Location

Institut Català d'Oncología (ICO) L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Consorcio Hospitalario Provincial de Castellón

Castellon, Castelló, 12002, Spain

Location

Hospital Universitario Donostia

San Sebastián, Donostia, 20014, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06080, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Universitario San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Institut Català d'Oncología (ICO) Girona

Girona, 17007, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Clínico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, 38010, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Virgen de la Salud

Toledo, 45004, Spain

Location

Fundación Instituto Valenciano de Oncología (FIVO)

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politécnic La Fe

Valencia, 46026, Spain

Location

Hospital Universitario Reina Sofía

Valencia, 46026, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; liposomal doxorubicin; Cyclophosphamide; taxane; Paclitaxel; Docetaxel; Letrozole; abemaciclib; Gonadotropin-Releasing Hormone; Goserelin; Leuprolide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

The open-label design may have introduced biases in treatment and tumor response evaluation. We prioritized RCB 0-I as the main endpoint, which does not directly reflect long-term survival outcomes like EFS or OS. Restricting to Ki-67 ≥20% limits relevance for low-proliferative HR+/HER2- tumors where endocrine therapy may work better. The lack of data on initial surgical intent and irradiation volumes, constrains the interpretation of the de-escalation outcomes (not collected prospectively).

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group (GEICAM)

geicam@geicam.org

+34916592870

Study Officials

• Study Director

  Hospital General Universitario Gregorio Marañon

  STUDY DIRECTOR

• Study Director

  Hospital Universitario Virgen de la Victoria

  STUDY DIRECTOR

• Study Director

  Instituto Valenciano de Oncología

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 3, 2020
• Study Start: October 2, 2020
• Primary Completion: June 21, 2023
• Study Completion (Estimated): February 28, 2033
• Last Updated: March 12, 2026
• Results First Posted: March 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (28)