Clinical Trials /

Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases

NCT04585724

Description:

This phase I trial studies the side effects of stereotactic radiosurgery with abemaciclib, ribociclib, or palbociclib in treating patients with hormone receptor positive breast cancer that has spread to the brain (brain metasteses). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Abemaciclib, ribociclib, and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib, ribociclib, or palbociclib concurrently with stereotactic radiosurgery may reduce the side effects and/or increase the response to each of the therapies.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stereotactic Radiosurgery With Abemaciclib, Ribociclib, or Palbociclib in Treating Patients With Hormone Receptor Positive Breast Cancer With Brain Metastases
  • Official Title: Evaluation of Radiosurgery With Concurrent Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: STUDY00000194
  • SECONDARY ID: NCI-2019-02251
  • SECONDARY ID: RAD4615-19
  • SECONDARY ID: P30CA138292
  • NCT ID: NCT04585724

Conditions

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Metastatic Breast Carcinoma
  • Metastatic Malignant Neoplasm in the Brain
  • Prognostic Stage IV Breast Cancer AJCC v8

Interventions

DrugSynonymsArms
AbemaciclibLY-2835219, LY2835219, VerzenioTreatment (abemaciclib)
Palbociclib6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991Treatment (palbociclib)
RibociclibKisqali, LEE-011, LEE011Treatment (ribociclib)

Purpose

This phase I trial studies the side effects of stereotactic radiosurgery with abemaciclib, ribociclib, or palbociclib in treating patients with hormone receptor positive breast cancer that has spread to the brain (brain metasteses). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Abemaciclib, ribociclib, and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib, ribociclib, or palbociclib concurrently with stereotactic radiosurgery may reduce the side effects and/or increase the response to each of the therapies.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Prospectively evaluate safety and toxicity of the combination of radiosurgery (SRS) and
      concurrent CDK 4/6 inhibitors (CDKi) for hormone receptor positive (HR+) breast cancer
      patients.

      SECONDARY OBJECTIVES:

      I. Evaluate late toxicity (after 3 months) following SRS and concurrent CDKi. II. Evaluate
      local control efficacy with combination therapy of SRS and concurrent CDKi.

      III. Assess quality of life and neurologic functional outcomes following treatment using
      standardized questionnaire (Functional Assessment of Cancer Therapy-Brain [FACT-Br]).

      IV. Analyze overall survival.

      OUTLINE: Patients are assigned to 1 of 3 groups.

      GROUP I: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive
      abemaciclib orally (PO) twice daily (BID). Treatment continues in the absence of disease
      progression or unacceptable toxicity.

      GROUP II: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive
      ribociclib PO once daily (QD) on days 1-21. Treatment continues in the absence of disease
      progression or unacceptable toxicity.

      GROUP III: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive
      palbociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 4-6 weeks post
      stereotactic radiosurgery, and then every 3 months for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abemaciclib)ExperimentalBeginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • Abemaciclib
Treatment (palbociclib)ExperimentalBeginning within 2 weeks prior to stereotactic radiosurgery, patients receive palbociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • Palbociclib
Treatment (ribociclib)ExperimentalBeginning within 2 weeks prior to stereotactic radiosurgery, patients receive ribociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity.
  • Ribociclib

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologic diagnosis of hormone receptor positive (estrogen receptor >= 1 percent or
             progesterone receptor >= 1 percent) with HER2 negative status, past treatment, or
             systemic disease status with current clinical diagnosis of up to 10 brain metastases
             based on contrast-enhanced magnetic resonance imaging (MRI) of the brain

          -  Plan to start or currently receiving an Food and Drug Administration (FDA)-approved
             CDK4/6 inhibitor (CDKi), which must be started no later than 2 weeks prior to planned
             radiosurgery with plan to continue CDKi following radiosurgery

          -  Up to 10 brain metastases =< 3 centimeters in greatest dimension, measured on
             radiation planning MRI

          -  Eastern Cooperative Oncology Group (ECOG)/Zubrod 0-1, or Karnofsky performance status
             70-100

          -  Contrast-enhanced MRI brain within 4 weeks of radiosurgical intervention (radiation
             planning MRI)

          -  Patients must be able to sign informed consent prior to study entry, including assent
             to standard of care post-treatment surveillance contrast-enhanced magnetic resonance
             imaging of the brain

          -  Patients who are enrolled in the study, and who continue to be prescribed CDK4/6
             inhibitor therapy and develop new brain metastases deemed treatable by radiosurgery,
             are specifically allowed to be re-treated while on study, and the new treated lesions
             will be separately counted by treatment category (1 to 3, 4 to 6, or 7 to 10 new
             treated lesions)

          -  Patients with prior treated brain metastases (radiosurgery, hypofractionated
             radiotherapy, or surgery) are eligible for the study regardless of prior history of
             asymptomatic or symptomatic radiation necrosis and may not be excluded from the study
             if that is the sole basis for exclusion

        Exclusion Criteria:

          -  Patients with current or prior invasive malignancy unless disease free for minimum of
             1 year

          -  Brain metastases > 3 cm

          -  Brain lesions causing midline shift or herniation > 1 cm

          -  Patients with unirradiated post-neurosurgical metastasectomy resection cavities,
             unless disease-free in the surgical bed for >= 6 months, are prohibited from pilot
             study enrollment

          -  No patients who require resection cavity radiation for treatment of a resected brain
             metastasis (i.e.: standard of care treatment) are eligible for enrollment

          -  Receipt of chemotherapeutic agents (other than CDK4/6 inhibitors or hormone
             receptor-related targeted agents) within 2 weeks of planned radiosurgery date

          -  Prior whole brain or craniospinal radiotherapy

          -  Fractionated radiation to unrelated central nervous system (CNS) tumor

          -  Concurrent malignant CNS tumor

          -  Recurrent or progressive brain metastasis necessitating surgical or medical
             intervention (i.e.: a non-radiotherapy intervention such as steroids)

          -  Recurrence or progressive brain metastasis from prior surgical resection necessitating
             surgical or medical intervention (i.e.: a non-radiotherapy intervention)

          -  Brain stem metastasis >= 1 cm

          -  Patients with scleroderma

          -  Severe acute co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization in the
                  last 3 months

               -  Transmural myocardial infarction within the last 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization in the last 6 months or precluding study therapy due to
                  inability to rest supine at the time of registration
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of grade 3+ radiation therapy oncology central nervous system toxicity
Time Frame:At 3 months
Safety Issue:
Description:Rate and frequency of grade 3+ toxicity will be reported. A 95% exact confidence interval will be estimated using the Clopper-Pearson method.

Secondary Outcome Measures

Measure:Symptomatic radiation necrosis (late toxicity)
Time Frame:At 6 and 12 months
Safety Issue:
Description:Will be defined as radiographic (typically on magnetic resonance imaging) changes consistent with radiation induced necrosis and the patient presenting with increased neurological symptoms. Rate and frequency of late toxicity will be reported, and a 95% exact confidence interval will be estimated. Symptomatic radiation necrosis similarly will be summarized. The rate of radiation necrosis will be compared with that of our institutional historical control.
Measure:Intracranial failure within treated lesion
Time Frame:Up to 1 year
Safety Issue:
Description:Will be defined by progressive lesion either biopsy-proven or with imaging interpretation concordance by both radiation oncologist and neuroradiologist on serial imaging. The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
Measure:Distant intracranial failure
Time Frame:Up to 1 year
Safety Issue:
Description:New lesions will be defined by new contrast-enhancing brain lesions on magnetic resonance imaging. The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
Measure:Overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate the overall survival rates.
Measure:Quality of life (QoL)
Time Frame:Up to 1 year
Safety Issue:
Description:Will be assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) at pre- and post-radiosurgery. Will be summarized using frequencies and percentages for categorical variables, and mean, standard deviation, median, and range for continuous variables. Paired tests such as paired t-tests and McNemar's tests will be considered for comparing QoL outcomes pre- versus post-radiosurgery.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

Last Updated

October 7, 2020