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

University of Washington

Status and phase

Enrolling

Phase 2

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Anatomic Stage III Breast Cancer AJCC v8

Locally Advanced Unresectable HER2-Negative Breast Carcinoma

Metastatic HER2-Negative Breast Carcinoma

Locally Advanced Unresectable Hormone Receptor-Positive Breast Carcinoma

Metastatic Hormone Receptor-Positive Breast Carcinoma

Treatments

Drug: Fulvestrant

Drug: Exemestane

Drug: Abemaciclib

Procedure: Positron Emission Tomography

Drug: Letrozole

Biological: Gonadotropin-releasing Hormone Analog

Procedure: Computed Tomography

Other: Fludeoxyglucose F-18

Drug: Fluorine F 18 Fluoro Furanyl Norprogesterone

Procedure: Biospecimen Collection

Drug: Tamoxifen

Drug: Anastrozole

Drug: Therapeutic Estradiol

Procedure: Diagnostic Imaging Testing

Study type

Interventional

Funder types

Other

Identifiers

NCT06179303

NCI-2022-06409 (Registry Identifier)

RG1122019 (Other Identifier)

FHIRB0020029 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

60 participants in 1 patient group

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

Experimental group

Description:

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: