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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-002123-15 | EudraCT Number |
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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 weeks of treatment |
| RCB 0+I Versus RCB-II Versus RCB-III |
Not provided
Inclusion Criteria:
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.
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:
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:
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.
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Complejo Hospitalario Universitario de Santiago (CHUS) | Santiago de Compostela | A Coruña | 15706 | Spain | ||
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| Label | URL |
|---|---|
| Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Doxorubicin Plus Cyclophosphamide and Taxane | 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). Doxorubicin: 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. Cyclophosphamide: 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. Taxane: 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 29, 2021 | Dec 2, 2025 |
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|
| 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. |
|
|
| 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. |
|
|
| 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 |
|
|
| 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 |
|
|
| 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 |
|
|
RCB is classified in four classes based on the residual disease (RD):
|
| 24 weeks |
| 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. | 24 weeks |
| 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. | 24 weeks |
| 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. | 24 weeks |
| 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:
| Up to 10 years |
| 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. | Through study treatment, and average of 12 months |
| 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. | 24 weeks |
| Institut Català d'Oncología (ICO) L'Hospitalet |
| L'Hospitalet de Llobregat |
| Barcelona |
| 08908 |
| Spain |
| Hospital Universitario Marqués de Valdecilla | Santander | Cantabria | 39008 | Spain |
| Consorcio Hospitalario Provincial de Castellón | Castellon | Castelló | 12002 | Spain |
| Hospital Universitario Donostia | San Sebastián | Donostia | 20014 | Spain |
| Hospital Álvaro Cunqueiro | Vigo | Pontevedra | 36312 | Spain |
| Complejo Hospitalario Universitario A Coruña (CHUAC) | A Coruña | 15006 | Spain |
| Hospital General Universitario de Alicante | Alicante | 03010 | Spain |
| Hospital Universitario de Badajoz | Badajoz | 06080 | Spain |
| Hospital Universitario de Burgos | Burgos | 09006 | Spain |
| Hospital Universitario San Pedro de Alcántara | Cáceres | 10003 | Spain |
| Hospital Universitario Reina Sofía | Córdoba | 14004 | Spain |
| Institut Català d'Oncología (ICO) Girona | Girona | 17007 | Spain |
| Complejo Hospitalario de Jaén | Jaén | 23007 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Universitario Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital Clínico San Carlos | Madrid | 28040 | Spain |
| Hospital Clínico Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital General Universitario Morales Meseguer | Murcia | 30008 | Spain |
| Hospital Universitario Nuestra Señora de Candelaria | Santa Cruz de Tenerife | 38010 | Spain |
| Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
| Hospital Virgen de la Salud | Toledo | 45004 | Spain |
| Fundación Instituto Valenciano de Oncología (FIVO) | Valencia | 46009 | Spain |
| Hospital Clínico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital Universitari i Politécnic La Fe | Valencia | 46026 | Spain |
| Hospital Universitario Reina Sofía | Valencia | 46026 | Spain |
| Hospital Clínico Universitario Lozano Blesa | Zaragoza | 50009 | Spain |
| Hospital Universitario Miguel Servet | Zaragoza | 50009 | Spain |
| FG001 | Arm B: Letrozole Plus Abemaciclib +/- LHRH | 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. Letrozole: 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 Abemaciclib: 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 Analogue: 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 |
| COMPLETED |
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| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Doxorubicin Plus Cyclophosphamide and Taxane | 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). Doxorubicin: 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. Cyclophosphamide: 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. Taxane: 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. |
| BG001 | Arm B: Letrozole Plus Abemaciclib +/- LHRH | 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. Letrozole: 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 Abemaciclib: 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 Analogue: 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) status | Measure Description: ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic
| Count of Participants | Participants |
| |||||||||||||||||
| Body Mass Index Category | Body Mass Index Category
| Count of Participants | Participants |
| |||||||||||||||||
| Menopausal Status | Count of Participants | Participants |
| ||||||||||||||||||
| Disease Stage | Disease staging is a system used to classify the extent and severity of a disease. It involves a set of criteria based on diagnostic findings like tumor size, lymph node involvement, and whether the disease has spread to other parts of the body.
| Count of Participants | Participants |
| |||||||||||||||||
| Ki67 Index | The Ki-67 index in breast cancer is a measure of how fast cancer cells are dividing, with a higher index indicating more aggressive, rapidly growing tumors. It is a prognostic and predictive biomarker used to assess the likelihood of recurrence and to help guide treatment decisions, particularly for chemotherapy. While generally considered a reliable indicator of proliferation, there are challenges with standardization that affect its use in routine clinical practice | Count of Participants | Participants |
| |||||||||||||||||
| Histopathologic Grade | Measure Description: Cancer cells are given a Grade (G) when they are removed from the breast and checked under a microscope. The G is based on how much the cancer cells look like normal cells.
| Count of Participants | Participants |
| |||||||||||||||||
| Multifocal tumor | Count of Participants | Participants |
| ||||||||||||||||||
| Multicentric tumor | Count of Participants | Participants |
| ||||||||||||||||||
| cT | cT is a marker in the TNM cancer staging system that describe the clinical extent of the tumor cT refers to the size and extent of the primary tumor. The "c" stands for "clinical" (evaluation before surgery, often using CT scans). cT (Clinical Primary Tumor): Indicates the size of the original tumor and whether it has invaded nearby tissues, based on imaging studies (such as CT) and physical examination. cT1: 2 cm or less cT2: 2 to 5 cm cT3: more than 5 cm cT4: Invades nearby structures | Count of Participants | Participants |
| |||||||||||||||||
| cN | cN is a marker in the TNM cancer staging system that describe the clinical extent of the tumor: cN refers to involvement of nearby lymph nodes. The "c" stands for "clinical" (evaluation before surgery, often using CT scans). cN (Clinical Lymph Nodes): Assesses whether the cancer has spread to regional lymph nodes near the tumor. cN0: No lymph node involvement cN1: 1-3 Lymph nodes affected cN2: 4-9 Lymph nodes affected | Count of Participants | Participants |
| |||||||||||||||||
| Hormonal Receptor status | Hormonal Receptor (HR) status, primarily in breast cancer, indicates if tumor cells have proteins (receptors) for estrogen (ER) or progesterone (PgR) hormones, determining if these hormones fuel cancer growth. HR-positive cancers have these receptors, respond to hormone therapies, and often grow slower, while HR-negative cancers lack them, won't benefit from hormone therapy, and may grow faster, guiding crucial treatment decisions. | Count of Participants | Participants |
| |||||||||||||||||
| HER2 status | HER2 status refers to the level of HER2 protein (Human Epidermal growth factor Receptor 2) on cancer cells; it determines if cells have too many copies of the HER2 gene, leading to aggressive growth but also making them targets for special HER2-targeted therapies, with results categorized as HER2-positive (high levels), HER2-negative (normal levels, 0 or 1+), or HER2-low (intermediate levels, 1+ or 2+ FISH negative), guiding treatment choices. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Count of Participants | Participants | Through study treatment, and average of 12 months |
|
|
| ||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | % KI67 dyed cells | 2 weeks of treatment |
| |||||||||||||||||||||||||||||||
| Secondary | RCB 0+I Versus RCB-II Versus RCB-III | RCB is classified in four classes based on the residual disease (RD):
| Posted | Count of Participants | Participants | 24 weeks |
| ||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | 24 weeks |
| ||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | 24 weeks |
| ||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | 24 weeks |
| ||||||||||||||||||||||||||||||||
| Secondary | 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:
| Not Posted | Up to 10 years | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | Through study treatment, and average of 12 months |
| ||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | 24 weeks | Participants |
AEs have been recorded through study completion, an average of 1 year.
AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Doxorubicin Plus Cyclophosphamide and Taxane | 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). Doxorubicin: 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. Cyclophosphamide: 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. Taxane: 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. | 1 | 100 | 7 | 100 | 97 | 100 |
| EG001 | Arm B: Letrozole Plus Abemaciclib +/- LHRH | 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. Letrozole: 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 Abemaciclib: 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 Analogue: 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 | 4 | 99 | 8 | 99 | 94 | 99 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Lymphocytic lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Plasma cell myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Rectal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Post procedural cellulitis | Infections and infestations | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Wound infection staphylococcal | Infections and infestations | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Varicocele utero-ovarian | Reproductive system and breast disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Embolism | Vascular disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Asthenia | General disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Rash and Other Skin disorder | Skin and subcutaneous tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | NCI CTC-AE v 5.0 | Systematic Assessment |
| |
| Vulvovaginal dryness | Reproductive system and breast disorders | NCI CTC-AE v 5.0 | Systematic Assessment |
|
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).
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scientific Director / Medical Lead / Project Manager | Spanish Breast Cancer Research Group (GEICAM) | +34916592870 | geicam@geicam.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 30, 2023 | Dec 2, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| C506643 | liposomal doxorubicin |
| D003520 | Cyclophosphamide |
| C080625 | taxane |
| D017239 | Paclitaxel |
| D000077143 | Docetaxel |
| D000077289 | Letrozole |
| C000590451 | abemaciclib |
| D007987 | Gonadotropin-Releasing Hormone |
| D017273 | Goserelin |
| D016729 | Leuprolide |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D009570 | Nitriles |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| ECOG 1 |
|
| normal weight |
|
| overweight |
|
| obese type I |
|
| obese type II |
|
| obese type III |
|
| Missing |
|
| Postmenopausal |
|
| Stage II B |
|
| Stage III A |
|
| Stage III B |
|
| >=30% |
|
| G2, Moderately Differentiated |
|
| G3, Poorly Differentiated |
|
| GX, Unknown |
|
| Not Available/Not Done |
|
| No |
|
| No |
|
| T2 |
|
| T3 |
|
| T4 |
|
| N1 |
|
| N2 |
|
| ER+/PgR- |
|
| ER+/PgR not available |
|
| HER2+ |
|
|
|
|
|
|
|
|
|
|
|
| OG001 | Arm B: Letrozole Plus Abemaciclib +/- LHRH | 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. Letrozole: 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 Abemaciclib: 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 Analogue: 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 |
|
|