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

Primary Purpose

Brain Metastases, HR+ Metastatic Breast Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Stereotactic Radiosurgery (SRS)
Abemaciclib
Endocrine therapy
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • Patients with prior history of nonbreast cancer malignancies should have no evidence of disease ≥ 2 years
  • 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

Sites / Locations

  • Moffitt Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1: Radiation Therapy and Abemaciclib

Phase 2: Radiation Therapy and Abemaciclib

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Intracranial Progression Free Survival (PFS)
Intracranial Progression Free Survival: defined as the time from the date of start of treatment to investigator-determined date of progression or death due to any cause, whichever comes first. Progression will be determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria.

Secondary Outcome Measures

Intracranial local brain tumor control
Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.
Intracranial distant brain tumor control
Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.
Extracranial Progression Free Survival
Extracranial Progression Free Survival: Time from the date of start of treatment to the investigator determined date of progression (determined by RECIST) or death due to any cause, whichever occurs first.
Overall Survival
Overall Survival is defined as the time from the start of treatment to death due to any cause.

Full Information

First Posted
June 8, 2021
Last Updated
August 16, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT04923542
Brief Title
Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases
Official Title
Phase I/II Study of Stereotactic Radiation and Abemaciclib in the Management of Hormone Receptor Positive HER2 Negative Breast Cancer Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases, HR+ Metastatic Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: Radiation Therapy and Abemaciclib
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: Radiation Therapy and Abemaciclib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Radiosurgery (SRS)
Intervention Description
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
Drug
Intervention Name(s)
Abemaciclib
Other Intervention Name(s)
Verzenio, Ramiven
Intervention Description
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
Intervention Name(s)
Endocrine therapy
Other Intervention Name(s)
hormone therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Intracranial Progression Free Survival (PFS)
Description
Intracranial Progression Free Survival: defined as the time from the date of start of treatment to investigator-determined date of progression or death due to any cause, whichever comes first. Progression will be determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Intracranial local brain tumor control
Description
Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.
Time Frame
Up to 12 months
Title
Intracranial distant brain tumor control
Description
Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.
Time Frame
Up to 12 months
Title
Extracranial Progression Free Survival
Description
Extracranial Progression Free Survival: Time from the date of start of treatment to the investigator determined date of progression (determined by RECIST) or death due to any cause, whichever occurs first.
Time Frame
Up to 12 months
Title
Overall Survival
Description
Overall Survival is defined as the time from the start of treatment to death due to any cause.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kamran A Ahmed, MD
Phone
813-745-8424
Email
Kamran.Ahmed@moffitt.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kamran A Ahmed, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Heather Han, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle DeJesus
Phone
813-745-6911
Email
Michelle.DeJesus@moffitt.org
First Name & Middle Initial & Last Name & Degree
Avan Armaghani, MD
First Name & Middle Initial & Last Name & Degree
John Arrington, MD
First Name & Middle Initial & Last Name & Degree
Ricardo Costa, MD, MSc
First Name & Middle Initial & Last Name & Degree
Arnold Etame, MD, PhD
First Name & Middle Initial & Last Name & Degree
Peter Forsyth, MD
First Name & Middle Initial & Last Name & Degree
Hung Khong, MD
First Name & Middle Initial & Last Name & Degree
James Liu, MD
First Name & Middle Initial & Last Name & Degree
Daniel Oliver, MD
First Name & Middle Initial & Last Name & Degree
Marilin Rosa, MD
First Name & Middle Initial & Last Name & Degree
Hatem Soliman, MD
First Name & Middle Initial & Last Name & Degree
Aixa Soyano Muller, MD
First Name & Middle Initial & Last Name & Degree
Nam Tran, MD, PhD
First Name & Middle Initial & Last Name & Degree
Michael Vogelbaum, MD, PhD
First Name & Middle Initial & Last Name & Degree
Michael Yu, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://moffitt.org/clinical-trials-research/clinical-trials/?source=footer
Description
Moffitt Cancer Center's Clinical Trials Website

Learn more about this trial

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

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