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

Phase 2

Recruiting

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

• Registration Number: NCT06179303
• Lead Sponsor: University of Washington

Brief Summary

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 t...

Detailed Description

OUTLINE:
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2023-12-08
• Study First Submitted QC: 2023-12-11
• Study First Posted: 2023-12-21
• Status Verified: 2024-03
• Study Start: 2024-07-22
• Last Update Submitted: 2024-08-05
• Last Update Posted: 2024-08-07
• Primary Completion: 2025-03-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Biospecimen Collection	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Diagnostic Imaging	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Computed Tomography	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Therapeutic Estradiol	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Fluorine F 18 Fluoro Furanyl Norprogesterone	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Fludeoxyglucose F-18	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Gonadotropin-releasing Hormone Analog	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Positron Emission Tomography	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Anastrozole	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Abemaciclib	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Exemestane	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Fulvestrant	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Letrozole	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.
Treatment (FFNP-PET/CT, estradiol, abemaciclib, ET)	Tamoxifen	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.

Primary Outcome Measures

Name	Time	Method
Response to abemaciclib + endocrine therapy	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...

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	Up to 2 years	Defined by RECIST 1.1
Progression free survival rate (PFS)	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.
Overall survival rate (OS)	Up to 2 years	Defined from date on study to date of death or last follow up if a patient is still alive.

Trial Locations

Locations (2)

Siteman Cancer Center at Washington University; 🇺🇸 Saint Louis, Missouri, United States

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States