Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

NCT ID: NCT06179303

Last Updated: 2025-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-22

Study Completion Date

2028-06-01

Brief Summary

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This phase II trial tests the accuracy of functional imaging (FFNP)-positron emission tomography (PET)/computed tomography (CT) to predict response to abemaciclib plus endocrine therapy. Abemaciclib is a drug used to treat certain types of hormone receptor positive (HR+), HER2 negative breast cancer. Abemaciclib blocks certain proteins, which may help keep tumor cells from growing. Endocrine therapy adds, blocks, or removes hormones that can cause cancer to grow. FFNP PET imaging is a form of x-ray that uses FFNP as an imaging agent that may provide more precise information about the location of tumors that "light up" with FFNP than a PET scan alone can provide.

Detailed Description

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OUTLINE:

Patients receive FFNP intravenously (IV) and undergo PET/CT imaging at baseline. Patients then receive estradiol orally every 8 hours (Q8H) over a 24-hour period, followed again by FFNP IV and PET/CT imaging. Patients then receive abemaciclib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive endocrine therapy (ET) of the treating physician choice. Patients also receive FDG IV and undergo PET/CT imaging at baseline, with additional diagnostic imaging for tumor assessment every 3 cycles, and undergo blood sample collection throughout the study.

After study completion of study, patients are followed every 3 months.

Conditions

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Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 Locally Advanced Unresectable HER2-Negative Breast Carcinoma Locally Advanced Unresectable Hormone Receptor-Positive Breast Carcinoma Metastatic HER2-Negative Breast Carcinoma Metastatic Hormone Receptor-Positive Breast Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)

Patients receive FFNP IV and undergo PET/CT imaging at baseline. Patients then receive estradiol orally Q8H over a 24-hour period, followed again by FFNP IV and PET/CT imaging. Patients then receive abemaciclib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive ET of the treating physician choice. Patients also receive FDG IV and undergo PET/CT imaging at baseline, with additional diagnostic imaging for tumor assessment every 3 cycles, and undergo blood sample collection throughout the study.

Group Type EXPERIMENTAL

Fluorine F 18 Fluoro Furanyl Norprogesterone

Intervention Type DRUG

Given IV

Fulvestrant

Intervention Type DRUG

Given IM injection

Gonadotropin-releasing Hormone Analog

Intervention Type BIOLOGICAL

Given GnRH analog

Letrozole

Intervention Type DRUG

Given PO

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Tamoxifen

Intervention Type DRUG

Given PO

Therapeutic Estradiol

Intervention Type DRUG

Given PO

Abemaciclib

Intervention Type DRUG

Given PO

Anastrozole

Intervention Type DRUG

Given PO

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Diagnostic Imaging Testing

Intervention Type PROCEDURE

Undergo clinical imaging for tumor assessment

Exemestane

Intervention Type DRUG

Given PO

Fludeoxyglucose F-18

Intervention Type OTHER

Given IV

Interventions

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Fluorine F 18 Fluoro Furanyl Norprogesterone

Given IV

Intervention Type DRUG

Fulvestrant

Given IM injection

Intervention Type DRUG

Gonadotropin-releasing Hormone Analog

Given GnRH analog

Intervention Type BIOLOGICAL

Letrozole

Given PO

Intervention Type DRUG

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Tamoxifen

Given PO

Intervention Type DRUG

Therapeutic Estradiol

Given PO

Intervention Type DRUG

Abemaciclib

Given PO

Intervention Type DRUG

Anastrozole

Given PO

Intervention Type DRUG

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Diagnostic Imaging Testing

Undergo clinical imaging for tumor assessment

Intervention Type PROCEDURE

Exemestane

Given PO

Intervention Type DRUG

Fludeoxyglucose F-18

Given IV

Intervention Type OTHER

Other Intervention Names

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LY-2835219 LY2835219 Verzenio Anastrazole Arimidex ICI D1033 ICI-D1033 ZD-1033 Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Diagnostic Imaging Medical Imaging Aromasin FCE-24304 18FDG FDG Fludeoxyglucose (18F) fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 [18F]FFNP Faslodex Faslodex(ICI 182,780) ICI 182,780 ICI 182780 ZD9238 GnRH Agonist GnRH Analog Gonadotropin-Releasing Hormone Agonist Gonadotropin-Releasing Hormone Analogue LH-RH agonist LH-RH Analogs LHRH Agonist luteinizing hormone-releasing hormone agonist Luteinizing Hormone-Releasing Hormone Analog CGS 20267 Femara Fempro Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT TMX 17 Beta-Estradiol Aquadiol Climara Dimenformon Diogyn Diogynets Estrace ESTRADIOL Estraldine Oestradiol Ovocylin Progynon Vagifem

Eligibility Criteria

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Inclusion Criteria

* Men or women with metastatic or locally advanced unresectable breast cancer
* Histologically confirmed ER+ / HER2-negative, breast cancer who is a candidate for endocrine therapy with pathology from the primary tumor or metastatic/recurrent site. Based on American Society of Clinical Oncology/College of American Pathologists (ASCO CAP) Guidelines: ER+: \>= 1% of tumor cell nuclei to be immunoreactive. HER2-negative: HER2 of 0, 1+ by immunohistochemistry (IHC) or negative by fluorescence in situ hybridization (FISH).

* In the case of bone biopsy which could yield false negative ER or PR status in patients with historically HR+ disease, a patient may be eligible if the treating physician and the study chair both agree that the patient is a candidate for further endocrine therapy (ET) based treatment.
* Note that baseline PR status by IHC does not influence results of deltaFFNP-PET imaging.
* If premenopausal, the patient has to be treated with GnRH agonist for at least 6 weeks prior to FFNP-PET.
* Disease must be present in at least one non-liver site and measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and be 1.5 cm or greater in longest dimension OR disease can be non-measurable but must be 1.5 cm in longest dimension on functional imaging (fluorodeoxyglucose \[FDG\]-PET/computed tomography \[CT\] preferred).
* No limits to prior lines of endocrine therapy in the metastatic setting including synergistic targeted therapy such as CDK4/6 inhibitors (other than Abemaciclib), PI3K inhibitor, mTOR inhibitor, etc. One line of prior cytotoxic chemotherapy in the metastatic setting is allowed. Washout from prior systemic anti-cancer therapy of at least 2 weeks from chemotherapy or radiation, 2 weeks or 5 half lives (whichever is longer) from oral selective estrogen receptor degrader (SERD), 8 weeks from oral selective estrogen receptor modulator (SERM), and 16 weeks from intramuscular SERD (Fulvestrant) is required. Recovery of adverse events from the last therapy to grade 1 except alopecia. Patients may continue luteinizing hormone-releasing hormone (LHRH) agonist to remain post-menopausal without a need for washout
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* At least 18 years of age
* Absolute neutrophil count \>= 1,500/uL
* Platelets \>= 100,000/uL
* Hemoglobin \>= 9g/dL
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN).

* In case of known Gilbert's syndrome, \< 2 x ULN is allowed
* Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =\< 2.5x institutional ULN, or =\< 5 x ULN for subjects with documented metastatic disease to the liver
* eGFR (estimated glomerular filtration rate) ≥ 30 mL/min
* Women of childbearing potential must agree to use adequate contraception (barrier method of birth control, abstinence) prior to study entry and for the duration of study participation
* Ability to understand and willingness to sign an institutional review board (IRB)-approved written informed consent document (or that of legally authorizes representative, if applicable)
* Consent to access archival tumor specimens for clinical sequencing data of tumor tissue and blood

Exclusion Criteria

* Prior abemaciclib in the metastatic setting or within 2 years of completion of adjuvant abemaciclib
* Hepatic-only metastatic disease
* A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease
* Currently receiving any other investigational agents
* Untreated/unstable brain metastases. Patients with treated/stable brain metastases, defines as patients who have received prior therapy for their brain metastases and whose central nervous system (CNS) disease is radiographically stable at study entry, are eligible
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to FFNP, abemaciclib, or other agents used in the study
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
* Pregnant and/or breastfeeding women of childbearing potential must have a negative pregnancy test within 14 days of study entry. Male participants and female participants of childbearing potential must utilize adequate contraceptive methods throughout study treatment and for at least 30 days after the last dose of study medications
* Patients with human immunodeficiency virus (HIV) are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (DHHS) treatment guidelines is recommended
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Breast Cancer Research Foundation

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hannah Linden

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Siteman Cancer Center at Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Hannah Linden

Role: CONTACT

206-606-2053

Facility Contacts

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Farrokh Dehdashti

Role: primary

314-362-2809

Hannah Linden

Role: primary

206-606-2053

Other Identifiers

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NCI-2022-06409

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020029

Identifier Type: OTHER

Identifier Source: secondary_id

RG1122019

Identifier Type: -

Identifier Source: org_study_id

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