Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases

NCT ID: NCT04923542

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2026-03-31

Brief Summary

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This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.

Detailed Description

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The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases. Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. Safety will be monitored initially by a 3+3 design. This will be followed by a phase 2 study to evaluate intracranial progression free survival (PFS). If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

Conditions

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Brain Metastases HR+ Metastatic Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1: Radiation Therapy and Abemaciclib

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. In the phase I portion, safety will be monitored initially by a 3+3 design. If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

Group Type EXPERIMENTAL

Stereotactic Radiosurgery (SRS)

Intervention Type RADIATION

Patients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.

Abemaciclib

Intervention Type DRUG

Abemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.

Endocrine therapy

Intervention Type DRUG

Abemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.

Phase 2: Radiation Therapy and Abemaciclib

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities with continued abemaciclib.

Group Type EXPERIMENTAL

Stereotactic Radiosurgery (SRS)

Intervention Type RADIATION

Patients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.

Abemaciclib

Intervention Type DRUG

Abemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.

Endocrine therapy

Intervention Type DRUG

Abemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.

Interventions

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Stereotactic Radiosurgery (SRS)

Patients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.

Intervention Type RADIATION

Abemaciclib

Abemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.

Intervention Type DRUG

Endocrine therapy

Abemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.

Intervention Type DRUG

Other Intervention Names

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Verzenio Ramiven hormone therapy

Eligibility Criteria

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Inclusion Criteria

* HR+ breast cancer to fulfill the requirement of HR+ disease, a breast cancer must express (≥ 1%), by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor \[ER\] or progesterone receptor \[PR\]) as defined in the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Guidelines
* To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines
* ≤ 15 brain metastases eligible for stereotactic radiation
* Able to swallow oral medications
* Willing to comply with all study procedures and available for duration of the study
* Measurable brain disease per RANO-BM criteria that can be measured in at least one dimension as ≥ 0.5 cm for both intact brain metastases and post-operative cavities
* Eligible for SRS to brain metastases or to the post-operative bed following surgical resection
* Maximum diameter of the largest intact brain metastases ≤ 4 cm
* Eastern Cooperative Oncology Group performance status 0 to 2
* A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. If attempts to obtain archival tissue are unsuccessful the patient may be enrolled.
* Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will be allowed if active measurable disease has not previously been treated with radiation therapy
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 7 days of the first dose of abemaciclib
* WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s), and for three weeks following the last dose of abemaciclib
* Adequate organ function as defined in protocol

Exclusion Criteria

* Presence of leptomeningeal disease
* Prior receipt of whole brain radiation therapy
* Prior receipt of abemaciclib in the setting of brain metastases or in the past 6 months for the treatment of metastatic disease.
* All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) other than: a. Toxicities attributed to prior anticancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy b. Toxicities that are not expected to interfere with study treatment, such as fatigue, alopecia, or grade 2 hematologic toxicity
* Women who are pregnant or breastfeeding
* The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
* The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment
* The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
* History of prior malignancy within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of \>90%), such as but not limited to, non-melanoma skin carcinoma, or stage I endometriod uterine cancer, and others at the discretion of the PI.
* Major surgery or significant traumatic injury that has not been recovered from by 14 days before the initiation of study drug
* Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of first dose of study treatment
* History of allergy or hypersensitivity to any of the study drugs or study drug components
* Prisoners or individuals who are involuntarily incarcerated
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kamran A Ahmed, MD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Heather Han, MD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

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Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kamran A Ahmed, MD

Role: CONTACT

Phone: 813-745-8424

Email: [email protected]

Facility Contacts

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Robin Dowell

Role: primary

Other Identifiers

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MCC-20899

Identifier Type: -

Identifier Source: org_study_id