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Early Breast CancerPhase 2CARABELANCT04293393

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

A Phase 2 study testing Doxorubicin, Cyclophosphamide and Taxane in people with Early Breast Cancer, run by Spanish Breast Cancer Research Group at 28 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Early Breast Cancer
What is being tested?
Doxorubicin, Cyclophosphamide and Taxane
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
28 sitesSpain
Study dates
2 Oct 2020to 28 Feb 2033
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.
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  • 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.
  • Patients diagnosed with multifocal or multicentric breast cancer will be eligible for the study if only 2 tumor lesions have been confirmed in the clinical evaluation and both lesions comply with the characteristics required by the protocol (please, refer to previous inclusion criteria).
  • 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
  • Age ≥ 60 years, or
  • Age < 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Folliculostimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges.
  • All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Patients are able to swallow oral medications.
  • Adequate organ and bone marrow function:
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5x109/L);
  • Platelets ≥ 100,000/mm3 (100x109/L);
  • Hemoglobin (Hgb) ≥ 8g/dL (80g/L) (erythrocyte transfusions are permitted; initial treatment must not begin earlier than the day after the erythrocyte transfusion);
  • Total serum bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (≤ 2x ULN and direct bilirubin within normal limits if Gilbert´s disease);
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3x ULN.
  • Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
  • For premenopausal women: agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 weeks after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception. Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
  • Negative serum pregnancy test within 7 days of the first dose of abemaciclib for premenopausal women, and for women who have experienced menopause onset < 12 months prior to first dose of therapy.
  • Patients consent to biological sample provision for biomarker exploratory analyses.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

Spain28 sites

  • Complejo Hospitalario Universitario A Coruña (CHUAC)

    A Coruña, 15006

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Hospital Universitario de Badajoz

    Badajoz, 06080

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Hospital Universitario San Pedro de Alcántara

    Cáceres, 10003

  • Consorcio Hospitalario Provincial de Castellón

    Castellon, Castelló, 12002

  • Hospital Universitario Reina Sofía

    Córdoba, 14004

  • Institut Català d'Oncología (ICO) Girona

    Girona, 17007

  • Complejo Hospitalario de Jaén

    Jaén, 23007

  • Institut Català d'Oncología (ICO) L'Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Clínico Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital General Universitario Morales Meseguer

    Murcia, 30008

  • Hospital Universitario Donostia

    San Sebastián, Donostia, 20014

  • Hospital Universitario Nuestra Señora de Candelaria

    Santa Cruz de Tenerife, 38010

  • Hospital Universitario Marqués de Valdecilla

    Santander, Cantabria, 39008

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela, A Coruña, 15706

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Virgen de la Salud

    Toledo, 45004

  • Fundación Instituto Valenciano de Oncología (FIVO)

    Valencia, 46009

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Universitari i Politécnic La Fe

    Valencia, 46026

  • Hospital Universitario Reina Sofía

    Valencia, 46026

  • Hospital Álvaro Cunqueiro

    Vigo, Pontevedra, 36312

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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

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

Read the detailed description

This is an international, multicenter, open-label, randomized phase II study in the neoadjuvant setting.

Approximately 200 premenopausal and postmenopausal women with Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2) negative Breast Cancer (BC) of intermediate/high risk determined by Ki67 index ≥ 20% on untreated breast tissue and centrally assessed, with indication of neoadjuvant treatment, will be included. Patients with Early Breast Cancer (EBC) on stages II-III (tumor size (T) > 2cm - T3, T4b, and lymph node involvement (N) N0-2) according to the 8th edition of the Union for International Cancer Control (UICC) TNM Classification. The subgroup with tumors T2 N0 will include high risk patients based on Ki67 index > 30% or Ki67 index between 20% and 30% and Progesterone Receptor (PgR) negative and/or histological grade 3.

Patients will be stratified according to the disease stage (II vs. III), menopausal status (premenopausal vs. postmenopausal) and Ki67 index (Ki67 < 30% vs. Ki67 ≥ 30%).

Once the screening process (locally at site and at the central laboratory) is completed, fully eligible patients will be randomized in a 1:1 fashion to the control arm with standard Chemotherapy (CT) based on anthracyclines and taxanes or to the experimental arm with letrozole + abemaciclib.

All patients will be treated according to the stipulations below, unless any of the following occur: unacceptable toxicity, progressive disease, or withdrawal of informed consent, whatever occurs first.

After the last dose of any of the drugs in the neoadjuvant combinations, in both treatment arms definitive surgery will be performed. For Arm A not earlier than 21 days and not later than 42 days after the last dose of chemotherapy, and for Arm B within 7 days from the last dose of abemaciclib and/or letrozole, unless toxicities are not recovered completely in any treatment arm.

Keywords
Abemaciclib, Neoadjuvant, HR positive, HER2 negative, High/intermediate risk
Medical subject headings
Breast Neoplasms

What participants receive

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

  • DoxorubicinDrug

    Also called Caelyx

    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.

  • CyclophosphamideDrug

    Also called Genoxal

    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.

  • TaxaneDrug

    Also called Paclitaxel, Docetaxel

    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.

  • LetrozoleDrug

    Also called Femara

    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

  • AbemaciclibDrug

    Also called Verzenios

    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

  • LHRH AnalogueDrug

    Also called Goserelin, Leuprolide

    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

Study groups in NCT04293393
Study groupRoleWhat they receive
Arm A: Doxorubicin plus cyclophosphamide and taxaneActive comparatorDoxorubicin 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).
Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Taxane
Arm B: Letrozole plus abemaciclib +/- LHRHExperimentalLetrozole 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.
Receives: Drug: Letrozole; Drug: Abemaciclib; Drug: LHRH Analogue

What is being measured

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

  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

    Measured: Through study treatment, and average of 12 months

Secondary outcomes (8)

  1. Changes in Percentage of KI67 Dyed Cells

    The percentage of decrease in the geometric mean of Ki67 after 2 weeks of treatment in both treatments arms.

    Number of patients with cell cycle arrest (Ki67 < 2.7%) after 2 weeks of treatment in both treatment arms.

    Measured: 2 weeks of treatment

  2. RCB 0+I Versus RCB-II Versus RCB-III

    RCB is classified in four classes based on the residual disease (RD):

    • RCB-0 defined as pathological complete response.
    • RCB-I defined as minimal RD.
    • RCB-II defined as moderate RD.
    • RCB-III defined as extensive RD.

    Measured: 24 weeks

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

    PEPI requires pathological stage (tumor size and nodal status), level of Ki67 protein, and Allred ER score measured on the surgical specimen.

    PEPI score 0 includes pT1 or pT2, pN0, Ki67 ≤ 2.7%, Allred score > 2. Patients with a PEPI score of 0 are found to have a low risk of recurrence.

    Measured: 24 weeks

  4. Clinical Response Measured by Magnetic Resonance Imaging (MRI)

    According to RECIST v1.1 in both treatment arms. Clinical Response Rate (CRR) is defined as the proportion of subjects with complete or partial radiographic response. Complete Response (CR) and Partial Response (PR) definitions are assessed by MRI at baseline and prior to breast surgery, with or without regional lymph nodes surgery, and categorized according to percent reduction in tumor size.

    Measured: 24 weeks

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

    Rate of BCS: defined as the proportion of patients who achieved breast-conserving surgery between both treatment arms.

    Measured: 24 weeks

  6. iEFS (Invasive Event Free Survival) in Both Treatment Arms.

    Invasive event free survival (iEFS): defined as time from randomization to progressive disease or invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. Invasive disease recurrence is defined as:

    • Ipsilateral invasive breast tumor recurrence (including second primary invasive breast cancer): an invasive breast cancer involving the same breast parenchyma as the original primary lesion.
    • Ipsilateral regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, other regional lymph nodes, chest wall, and/or skin of the ipsilateral breast).
    • Distant recurrence (i.e., evidence of breast cancer in any anatomic site outside local and/or regional location and that has been either histologically confirmed or clinically diagnosed as recurrent invasive breast cancer)
    • Contralateral invasive breast cancer
    • Second primary invasive cancer of non-breast origin.

    Measured: Up to 10 years

  7. The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment

    Safety assessments were performed at baseline and during the study: Vital signs assessments (blood pressure, pulse and body temperature), measurement of left ventricular ejection fraction, standard 12-lead electrocardiogram, laboratory assessments (hemoglobin, White Blood Cell, Absolute Neutrophil Count, Lymphocytes, platelet count, fasting glucose, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, serum creatinine, sodium, potassium, total calcium, blood urea nitrogen (or urea), pregnancy test , ophthalmologic assessments (visual acuity testing, slit lamp examination, fundoscopy), Viral serology.

    AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    The toxicity of study treatments will be evaluated in the safety population.

    Measured: Through study treatment, and average of 12 months

  8. To Assess Molecular Downstaging for High Risk Genomic Groups Defined by a Multigene Expression Panel.

    Gene expression data provided by a multigene expression panel in sequential tumor biopsies.

    Measured: 24 weeks

Timeline

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

  1. First posted3 Mar 2020
  2. Study start2 Oct 2020
  3. Primary completion21 Jun 2023
  4. Study completion28 Feb 2033 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04293393
Sponsor's protocol ID
GEICAM/2019-01
Other IDs
2019-002123-15, 2019
Acronym
CARABELA
Status last verified
Feb 2026
First submitted
28 Feb 2020
Last updated
12 Mar 2026
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxorubicin, Cyclophosphamide and Taxane in people with Early Breast Cancer, run by Spanish Breast Cancer Research Group at 28 sites in Spain.

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 32 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Residual Cancer Burden (RCB) 0-I Rate (time frame: Through study treatment, and average of 12 months). 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 NCT04293393.

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 12 Mar 2026.

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