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

March 15, 2024 updated by: University of Washington

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

Not yet recruiting

Conditions

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Washington University
        • Contact:
        • Principal Investigator:
          • Farrokh Dehdashti
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium
        • Contact:
        • Principal Investigator:
          • Hannah Linden

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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
  • 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

Exclusion Criteria:

  • Prior abemaciclib in the metastatic setting or within 2 years of completion of adjuvant abemaciclib
  • Hepatic-only metastatic 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
  • 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Procedure: Diagnostic Imaging
Undergo clinical imaging for tumor assessment
Other Names:
  • Medical Imaging
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to abemaciclib + endocrine therapy
Time Frame: Up to 2 years
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)
Time Frame: Up to 2 years
Defined by RECIST 1.1
Up to 2 years
Progression free survival rate (PFS)
Time Frame: Up to 2 years
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)
Time Frame: Up to 2 years
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

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Breast Cancer Research Foundation

Investigators

  • Principal Investigator: Hannah Linden, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

June 1, 2026

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)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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