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Anatomic Stage I Breast Cancer AJCC v8Phase 2NCT03979508

Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer

A Phase 2 study testing Abemaciclib and Therapeutic Conventional Surgery in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Abemaciclib and Therapeutic Conventional Surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
3 sitesUnited States
Study dates
10 Jan 2020to 26 Dec 2024
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

  • Women of age >=18 years
  • PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version 8.
  • Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed.
  • Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion.
  • PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor [ER] =< 10%, progesterone receptor [PR] =< 10% and HER2 not amplified by in situ hybridization [ISH] or immunohistochemistry [IHC] 0/1) at diagnosis.
  • PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
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  • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC)
  • Note: Carboplatin may be added to these regimens
  • AC or EC or FEC followed by docetaxel or paclitaxel
  • Note: Carboplatin may be added to these regimens
  • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
  • Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)
  • Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)
  • PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
  • Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens
  • AC or EC or FEC followed by docetaxel or paclitaxel [Note: Carboplatin may be added to these regimens]
  • Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
  • Docetaxel in combination with cyclophosphamide (TC)
  • Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel)
  • PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
  • PRE-REGISTRATION: Able to swallow oral medication.
  • PRE-REGISTRATION: Willing to undergo biopsy for research.
  • PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes.
  • PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
  • PRE-REGISTRATION: Provide written informed consent.
  • REGISTRATION: Registration must occur =< 56 days after last dose of NAC.
  • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.
  • REGISTRATION: COHORT B GROUP 4 ONLY: The following laboratory values obtained after completion of NAC but =< 14 days prior to registration:
  • REGISTRATION: COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) >= 1500/mm^3.
  • REGISTRATION: COHORT B GROUP 4 ONLY: Platelets (PLT) >= 100,000/mm^3.
  • REGISTRATION: COHORT B GROUP 4 ONLY: Hemoglobin (HgB) >= 8.0 g/dL.
  • REGISTRATION: COHORT B GROUP 4 ONLY: Total bilirubin =< 1.5 x upper limit of normal (ULN).
  • REGISTRATION: COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =< 3 x ULN.
  • REGISTRATION: COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN.
  • REGISTRATION: COHORT B GROUP 4 ONLY: Serum creatinine =< 1.5 x ULN.
  • REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.

Who cannot join

  • PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy.
  • NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
  • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
  • PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)
  • PRE-REGISTRATION: Prior treatment with radiation for this breast cancer.
  • PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.
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  • PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
  • PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
  • PRE-REGISTRATION: Other active malignancy =< 3 years prior to registration.
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
  • NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.
  • PRE-REGISTRATION: Biopsy proven Stage IV breast cancer.
  • PRE-REGISTRATION: Serious pre-existing medical conditions that 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 < 30 ml/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).
  • PRE-REGISTRATION: 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).
  • Sudden cardiac arrest.
  • NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
  • REGISTRATION: COHORT B GROUP 4: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons.
  • Nursing persons.
  • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • REGISTRATION: COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy.
  • Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed.
  • REGISTRATION: COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
  • REGISTRATION: COHORT B GROUP 4: Known infections as follows (NOTE: Screening is not required for enrollment):
  • Active systemic bacterial infection requiring intravenous antibiotics.
  • Active fungal infection (requiring intravenous or oral antifungal treatment).
  • Detectable viral infections (e.g. known human immunodeficiency virus [HIV], known active hepatitis B or C).
  • REGISTRATION: COHORT B GROUP 4: Concurrent use of chemotherapy, radiotherapy, immunotherapy, or other components of neoadjuvant treatment.
  • NOTE: Patients must complete all elements of NAC ≥21 days prior to starting abemaciclib.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*)

This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Abemaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy regimen without the addition of pembrolizumab (Cohort A).

II. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant TNBC patients following a neoadjuvant chemotherapy regimen with the addition of pembrolizumab (Cohort B).

SECONDARY OBJECTIVES for Cohort A and Cohort B Independently:

  1. Assess abemaciclib toxicities. II. To examine the effects of abemaciclib on the percentage of vimentin expressing invasive cancer cells

III. Within TNBC molecular subtypes (basal, mesenchymal, and luminal androgen receptor [LAR]), to evaluate the effects of abemaciclib on:

IIIa. The individual elements of tumor grade (mitoses, nuclear pleomorphism, and tubule formation).

IIIb. Tumor proliferation (as measured by tumor Ki-67 and serum tyrosine kinase inhibitor [TKI]).

IIIc. pDUB3 as well as epithelial-mesenchymal transition (EMT) markers including SNAIL/SLUG, TWIST, and E-Cadherin as measured by immunohistochemistry (IHC).

IIId. Quantification of tumor-infiltrating lymphocytes (as examined by hematoxylin and eosin [H\&E]).

EXPLORATORY OBJECTIVES for Cohort A and Cohort B Independently:

  1. To evaluate the effect of abemaciclib on tumor ribonucleic acid (RNA) expression.

II. To evaluate the effects of abemaciclib on the immune phenotype of peripheral blood mononuclear cells (PBMC), by evaluating expression of a panel of cell surface markers optimized of identification of human immune cell subpopulations.

III. To evaluate the effects of abemaciclib on tumor-infiltrating immune cells in formalin-fixed paraffin-embedded (FFPE) tumor sections, using multiplexed imaging technologies (e.g imaging mass cytometry, Nanostring digital spatial profiling [DSP] or CODEX) which will include:

IIIa. Genes directly involved in tumor cell antigen presentation (e.g. B2M, HLA-A, HLA-B, HLA-C, TAP1, TAP2, TAPBP).

IIIb. Interferon-stimulated genes (ISGs) that regulate antigen presentation (e.g. STAT1, NLRC5) and other ISGs (e.g. IRFs, OAS2).

IIIc. Genes involved in double-strand ribonucleic acid (dsRNA) response (e.g. DDX58, DHX58).

IIId. Genes encoding interferons, including type 3 IFNs (e.g. IFNL1, IFNL2, IFNL3).

IIIe. Genes indicating a cytotoxic T cell response (e.g. PRF1, GZMB). IIIf. Regulatory T-cell (Treg)-specific transcription factor genes (e.g. FOXP3, IKZF2).

IV. To assess the difference in the frequency of JAK-2 amplification among patients whose post-abemaciclib CD8/FOXP3 ratio >= 1.6 and that among patients whose post-abemaciclib CD8/FOXP3 ratio < 1.6.

  1. To generate organoids for future research. VI. To evaluate changes in the microbiome with exposure to abemaciclib.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive a neoadjuvant chemotherapy regimen without pembrolizumab.

GROUP 1: Patients undergo standard of care surgical resection.

GROUP 2: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.

After completion of study treatment, patients in group 2 are followed up within 30-60 days.

COHORT B: Patients receive a neoadjuvant chemotherapy regimen in combination with pembrolizumab.

GROUP 3: Patients undergo standard of care surgical resection.

GROUP 4: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.

After completion of study treatment, patients in group 4 are followed up within 30-60 days.

Medical subject headings
Carcinoma, Intraductal, Noninfiltrating, Fibrocystic Breast Disease, Breast Carcinoma In Situ, Triple Negative Breast Neoplasms

What participants receive

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

Study groups in NCT03979508
Study groupRoleWhat they receive
Cohort A Group 1; Cohort B Group 3 (surgery)ExperimentalPatients undergo standard of care surgical resection.
Receives: Procedure: Therapeutic Conventional Surgery
Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)ExperimentalPatients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.
Receives: Drug: Abemaciclib; Procedure: Therapeutic Conventional Surgery

What is being measured

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

  1. Number of Patients Who Have a CD8/FOXP3 Ratio < 1.6 in Their Residual Tumors After Neoadjuvant Chemotherapy (NAC) That Convert to CD8/FOXP3 Ratio >= 1.6

    A Simon optimum two stage phase II clinical trial design was chosen to test the null hypothesis that the rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is =< 5% against the alternative that rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is >= 20% with the target probability of a type I error and probability of a type II error set to 0.10. The probability of terminating after the first stage is 0.736, if the null hypothesis is true. A 90% confidence interval for this rate of conversion will be constructed using the Duffy-Santner approach taking into account the sequential nature of the study

    Measured: 21 days

Secondary outcomes (3)

  1. Number of Patients Experiencing a Grade 3 or Greater of Adverse Event

    Adverse events will be monitored and graded with attribution assigned using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of patients experiencing a grade 3 or greater AE will be reported

    Measured: 60 days

  2. Changes in Vimentin Expression

    Vimentin expression will be evaluated by immunohistochemistry (IHC) with using 0, 1+, 2+ or 3+ scoring scheme. A point estimate of the proportion of eligible patients whose post-NAC residual tumor Vimentin expression levels were 2+ or 3+ and then fell to 0 or 1+ after abemaciclib among the eligible patients whose began abemaciclib treatment after a post NAC residual tumor Vimentin expression level finding of 2+ or 3+ will be calculated. A 90% confidence interval for this proportion will be constructed using one-sample binomial confidence for proportions.

    Measured: 60 days

  3. Impact of Length of Treatment

    Association between amount of abemaciclib received and the change in CD8/FOXP3 ratio after abemaciclib will be explored graphically. A plot of the change in change in CD8/FOXP3 ratio after abemaciclib and days of treatment will be constructed to visually assess for trends. Also, the a 90% confidence interval for the difference in binomial proportions will be constructed to assess whether the proportion of patients whose post abemaciclib CD8/FOXP3 ratio >= 1.6 after completing 14-21 days of abemaciclib differs between those who discontinued abemaciclib the day prior to surgery and who discontinued abemaciclib 2 or more days prior to surgery. CD8/FOXP3 protein expression will be determined in tumor tissue obtained in residual invasive breast cancer obtained at surgery. Tissue samples will be frozen and processed centrally separate from the patient's progression through the study.

    Measured: 60 days

Timeline

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

  1. First posted7 Jun 2019
  2. Study start10 Jan 2020
  3. Primary completion26 Dec 2024
  4. Study completion26 Dec 2024

Why it stopped: The primary biomarker (CD8/FOXP3) was rarely observed to be \< 1.6 in residual tumors examined in first stage of study.

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03979508
Sponsor's protocol ID
MC1734
Other IDs
17-010660
Status last verified
Oct 2026
First submitted
5 Jun 2019
Last updated
2 Nov 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Abemaciclib and Therapeutic Conventional Surgery in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.

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 36 inclusion and 31 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: stopped early, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 2 Nov 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?

Number of Patients Who Have a CD8/FOXP3 Ratio < 1.6 in Their Residual Tumors After Neoadjuvant Chemotherapy (NAC) That Convert to CD8/FOXP3 Ratio >= 1.6 (time frame: 21 days). 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 NCT03979508.

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 2 Nov 2026.

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