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

A Phase II Trial to Evaluate Functional Imaging in Prediction of Response to Abemaciclib for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Metastatic HER2-Negative Breast Carcinoma; Metastatic Hormone Receptor-Positive Breast Carcinoma; Locally Advanced Unresectable HER2-Negative Breast Carcinoma; Locally Advanced Unresectable Hormone Receptor-Positive Breast Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Abemaciclib; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Other: Fludeoxyglucose F-18; Drug: Tamoxifen; Drug: Fluorine F 18 Fluoro Furanyl Norprogesterone; Biological: Gonadotropin-releasing Hormone Analog; Drug: Therapeutic Estradiol; Drug: Fulvestrant; Procedure: Diagnostic Imaging Testing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hannah Linden; Phone Number: 206-606-2053; Email: hmlinden@uw.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Siteman Cancer Center at Washington University
      • Contact: Farrokh Dehdashti; Phone Number: 314-362-2809; Email: dehdashtif@wustl.edu
      • Principal Investigator: Farrokh Dehdashti
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Hannah Linden; Phone Number: 206-606-2053; Email: hmlinden@uw.edu
      • Principal Investigator: Hannah Linden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Abemaciclib; Given PO; Other Names: LY-2835219; LY2835219; Verzenio; Procedure: Computed Tomography; Undergo PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Drug: Letrozole; Given PO; Other Names: CGS 20267; Femara; Fempro; Drug: Anastrozole; Given PO; Other Names: Arimidex; Anastrazole; ICI D1033; ICI-D1033; ZD-1033; Drug: Exemestane; Given PO; Other Names: Aromasin; FCE-24304; Other: Fludeoxyglucose F-18; Given IV; Other Names: 18FDG; FDG; fludeoxyglucose F 18; Fludeoxyglucose (18F); Fludeoxyglucose F18; Fluorine-18 2-Fluoro-2-deoxy-D-Glucose; Fluorodeoxyglucose F18; Drug: Tamoxifen; Given PO; Other Names: TMX; Drug: Fluorine F 18 Fluoro Furanyl Norprogesterone; Given IV; Other Names: [18F]FFNP; Biological: Gonadotropin-releasing Hormone Analog; Given GnRH analog; Other Names: 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; Drug: Therapeutic Estradiol; Given PO; Other Names: Climara; Estrace; Vagifem; 17 Beta-Estradiol; Aquadiol; Dimenformon; Diogyn; Diogynets; ESTRADIOL; Estraldine; Oestradiol; Ovocylin; Progynon; Drug: Fulvestrant; Given IM injection; Other Names: Faslodex; Faslodex(ICI 182,780); ICI 182,780; ICI 182780; ZD9238; Procedure: Diagnostic Imaging Testing; Undergo clinical imaging for tumor assessment; Other Names: Medical Imaging; Diagnostic Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to abemaciclib + endocrine therapy	Non-responding: progression within 24 weeks by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death due to disease within 24 weeks or stable disease but lasting less than 24 weeks. Responding: defined as complete response (CR), partial response (PR) or stable disease lasting >= 24 weeks. Quantitative deltaFFNP will be summarized by descriptive statistics (mean, median, standard deviation [SD], etc.) and tested against 0 by Wilcoxon signed rank test or paired t-test as appropriate, overall and by response. The dichotomized deltaFFNP will be summarized by count and percentages, overall and by response.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Defined by RECIST 1.1	Up to 2 years
Progression free survival rate (PFS)	Defined from date on study to date of progression or date of death or date of last clinical follow up with imaging evidence showing no progression if a patient did not progress or die, whichever the earliest. PFS events include progression and death.	Up to 2 years
Overall survival rate (OS)	Defined from date on study to date of death or last follow up if a patient is still alive.	Up to 2 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Breast Cancer Research Foundation
• Investigators: Principal Investigator: Hannah Linden, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Carcinoma; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Physical Phenomena; Hydrocarbons, Aromatic; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Benzene Derivatives; Nitriles; Chemistry Techniques, Analytical; Spectrum Analysis; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Electromagnetic Phenomena; Magnetic Phenomena; Deoxyglucose; Deoxy Sugars; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Triazoles; Stilbenes; Benzylidene Compounds; Letrozole; Fulvestrant; Anastrozole; Fluorodeoxyglucose F18; Tamoxifen; Estradiol; Gonadotropin-Releasing Hormone; Specimen Handling; abemaciclib; Magnetic Resonance Spectroscopy; X-Rays; exemestane
• Other Study ID Numbers: RG1122019 (Fred Hutch/University of Washington Cancer Consortium); NCI-2022-06409 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); FHIRB0020029 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No