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

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06179303
• Other study ID #: RG1122019
• Secondary ID: NCI-2022-06409FH
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 6, 2024
• Est. completion date: June 1, 2026

Study information

• Verified date: March 2024
• Source: University of Washington
• Contact: Hannah Linden
• Phone: 206-606-2053
• Email: hmlinden[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 1, 2026
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Neoplasms
• Carcinoma

Intervention

Drug:
• Abemaciclib
Given PO
• Anastrozole
Given PO

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo PET/CT
• Diagnostic Imaging
Undergo clinical imaging for tumor assessment

Drug:
• Exemestane
Given PO

Other:
• Fludeoxyglucose F-18
Given IV

Drug:
• Fluorine F 18 Fluoro Furanyl Norprogesterone
Given IV
• Fulvestrant
Given IM injection

Biological:
• Gonadotropin-releasing Hormone Analog
Given GnRH analog

Drug:
• Letrozole
Given PO

Procedure:
• Positron Emission Tomography
Undergo PET/CT

Drug:
• Tamoxifen
Given PO
• Therapeutic Estradiol
Given PO

Locations

Country	Name	City	State
United States	Siteman Cancer Center at Washington University	Saint Louis	Missouri
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Breast Cancer Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate (ORR)	Defined by RECIST 1.1	Up to 2 years
Secondary	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
Secondary	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