Clinical Trials /

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

NCT04923542

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-20899
  • NCT ID: NCT04923542

Conditions

  • Brain Metastases
  • HR+ Metastatic Breast Cancer

Interventions

DrugSynonymsArms
AbemaciclibVerzenio, RamivenPhase 1: Radiation Therapy and Abemaciclib
Endocrine therapyhormone therapyPhase 1: Radiation Therapy and Abemaciclib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Radiation Therapy and AbemaciclibExperimentalTreatment 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.
  • Abemaciclib
  • Endocrine therapy
Phase 2: Radiation Therapy and AbemaciclibExperimentalTreatment 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.
  • Abemaciclib
  • Endocrine therapy

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 for 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 ≥ 5 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intracranial Progression Free Survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
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.

Secondary Outcome Measures

Measure:Intracranial local brain tumor control
Time Frame:Up to 12 months
Safety Issue:
Description:Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.
Measure:Intracranial distant brain tumor control
Time Frame:Up to 12 months
Safety Issue:
Description:Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.
Measure:Extracranial Progression Free Survival
Time Frame:Up to 12 months
Safety Issue:
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.
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Survival is defined as the time from the start of treatment to death due to any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Last Updated

July 30, 2021