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Metastatic Breast CancerPhase 2NCT04352777

Impact of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer

A Phase 2 study testing Abemaciclib, Fulvestrant and Aromatase Inhibitors in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to perform an in depth analysis of changes in the tumor immune microenvironment in patients undergoing treatment with standard of care endocrine therapy and abemaciclib in the advanced setting via singe cell RNA sequencing. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Abemaciclib, Fulvestrant and Aromatase Inhibitors
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
14 Sep 2020to 25 Jun 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 age ≥ 18
  • Locally advanced/unresectable or metastatic breast cancer
  • Histologically documented estrogen receptor positive adenocarcinoma of the breast that is (any progesterone status allowed):
  • ER positive defined as ≥ 10 % tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity.
  • HER2 negative status is determined by:
  • IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of invasive tumor cells, or
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  • IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells, or
  • FISH negative based on:
  • Single-probe average HER2 copy number < 4.0 signals / cell, or
  • Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals /cell
  • Patients should have plans to initiate standard of care endocrine therapy with non-steroidal aromatase inhibitor (letrozole, anastrazole) OR fulvestrant plus abemaciclib in the advanced/metastatic first-line or second-line setting per treating oncologist discretion
  • Patients should be willing and able to undergo fresh biopsy pretreatment and at 4 weeks into treatment.
  • Patients should have an accessible lesion representative of recurrent or metastatic breast cancer for biopsy. Patients will undergo a tissue biopsy or tissue collection for research purposes only. Sites for tissue acquisition include the breast, skin/chest wall, soft tissue, liver, bone. Research directed lung biopsies and brain biopsies are not permitted. Procedures for tissue acquisition are restricted to those performed under local anesthesia or IV conscious sedation; biopsies that require general anesthesia are not permitted in this situation.
  • Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
  • Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy.
  • The patient is able to swallow oral medications.
  • The patient has adequate organ function for all of the following criteria, as defined in below.
  • Hematologic
  • ANC ≥1.5 × 10^9/L
  • Platelets ≥100 × 10^9/L
  • Hemoglobin ≥ 8 g/dL. * Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
  • Hepatic
  • Total bilirubin ≤1.5 × ULN *Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted.
  • ALT and AST ≤ 3 × ULN
  • Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.
  • Able and willing to complete the informed consent process
  • Agree to have bio-specimens stored for future research

Who cannot join

  • History of concurrent active malignancy within last 5 years (excluding basal cell skin cancer, resected squamous cell carcinoma of the skin)
  • Current use of hormonal birth control (copper IUD allowed) or estrogen replacement therapy
  • Active autoimmune disease that has required systemic treatment in past 6 months (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or similar treatment) is not considered a form of systemic treatment.
  • History of a serious or life-threatening allergic reaction to local anesthetics (e.g., lidocaine, xylocaine) used during a biopsy procedure
  • Immunodeficient subjects, E.G., receiving systemic steroid therapy greater than physiologic doses or any other form of immunosuppressive therapy within 30 days prior to the first dose of endocrine therapy treatment
  • Concurrent use of other oncologic therapies in the adjuvant setting other than bisphosphonates
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  • Patients with disease not amenable to biopsy
  • The patient has 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).
  • Females who are pregnant or lactating.
  • The patient has 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.
  • The patient has a 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.
  • History of bleeding disorder that would make serial biopsies unsafe.
  • Patients of active anticoagulation for history of venous thromboembolism, cardiovascular conditions.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Evaluation of the Effects of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer

The purpose of this study is to perform an in depth analysis of changes in the tumor immune microenvironment in patients undergoing treatment with standard of care endocrine therapy and abemaciclib in the advanced setting via singe cell RNA sequencing. The investigators will also correlate changes in serum estrogen levels to changes in tumor and peripheral immune cell repertoire and function (including regulatory T cell populations, B cells, myeloid-derived suppressor cell populations, T cell activation and T cell exhaustion).This study has two cohorts with 15 patients in each cohort.

Being tested
Abemaciclib, Fulvestrant, Aromatase Inhibitors
Keywords
metastatic breast cancer, abemaciclib, endocrine therapy
Medical subject headings
Breast Neoplasms

What participants receive

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

  • AbemaciclibDrug

    50 - 150mg tablet BID as prescribed per standard of care

  • FulvestrantDrug

    500mg as prescribed per standard of care

  • Aromatase InhibitorsDrug

    Letrozole, anastrozole as prescribed per standard of care

Study groups in NCT04352777
Study groupRoleWhat they receive
Cohort 1Active comparatorFulvestrant plus abemaciclib
Receives: Drug: Abemaciclib; Drug: Fulvestrant
Cohort 2Active comparatorAromatase inhibitor plus abemaciclib (with or without ovarian suppression)
Receives: Drug: Abemaciclib; Drug: Aromatase Inhibitors

What is being measured

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

  1. Changes in serum estrogen (E1 and E2) levels compared to changes in tumor immune cell repertoire and function in response to endocrine therapy and CDK 4/6 inhibition

    Estrogen levels in the blood will be assessed to correlate with changes in immune cell populations within the tumor.

    Measured: Through study completion, approximately 2 years

  2. Changes in serum estrogen (E1 and E2) levels compared to peripheral blood mononuclear cell repertoire and function in response to endocrine therapy and CDK 4/6 inhibition

    Estrogen levels in the blood will be assessed to correlate with changes in the characterization and functionality of peripheral blood mononuclear cells including regulatory T cell populations, B cells, myeloid-derived suppressor cell populations, T cell activation and T cell exhaustion.

    Measured: Through study completion, approximately 2 years

Secondary outcomes (6)

  1. Changes in tumor immune cell populations in response to fulvestrant and aromatase inhibitor therapy plus abemaciclib, measured by sequential biopsies

    Changes in tumor immune cell populations will be assessed by sequential biopsies via single cell RNA sequencing analysis of fresh tissue

    Measured: Baseline, 4 weeks

  2. Differences in tumor immune cell infiltrate and peripheral blood mononuclear cells in response to fulvestrant versus aromatase inhibition plus CDK4/6 inhibition, measured by sequential biopsies and blood collection

    Tumor immune cell and peripheral blood monoclonal cell changes assessed by sequential biopsies via single cell RNA sequencing analysis of fresh tissue

    Measured: Baseline, 4 weeks

  3. To correlate unique immune cell populations identified with progression free survival in the overall population

    Unique immune cell populations will be identified via single cell RNA sequencing and correlated to progression free survival measured by RECIST1.1.

    Measured: Through study completion, approximately 2 years

  4. Best overall response rate of abemaciclib and endocrine therapy in both treatment arms

    Best overall response rate to both treatment arms measured by RECIST 1.1

    Measured: Through study completion, approximately 2 years

  5. Progression free survival in response to abemaciclib and endocrine therapy in both treatment arms

    Progression free survival rate to both treatment arms measured by RECIST 1.1

    Measured: Through study completion, approximately 2 years

  6. Number of participants with at least one serious adverse event

    Serious adverse events will include only those related to abemaciclib, endocrine therapy, and/or study-related biopsies

    Measured: Through study completion, approximately 2 years

Timeline

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

  1. First posted20 Apr 2020
  2. Study start14 Sep 2020
  3. Primary completion25 Jun 2025
  4. Study completion25 Jun 2025

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04352777
Sponsor's protocol ID
Pro00103625
Status last verified
Jul 2025
First submitted
16 Apr 2020
Last updated
20 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Abemaciclib, Fulvestrant and Aromatase Inhibitors in people with Metastatic Breast Cancer and Locally Advanced Breast Cancer, run by Duke University at 1 site 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 27 inclusion and 13 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: finished, as of the sponsor's last update on 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Changes in serum estrogen (E1 and E2) levels compared to changes in tumor immune cell repertoire and function in response to endocrine therapy and CDK 4/6 inhibition (time frame: Through study completion, approximately 2 years). The study lists 2 primary outcomes in all. 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 NCT04352777.

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 20 Jul 2025.

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