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Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study

NCT04047602

Description:

This study will evaluate the rate of radiation necrosis following treatment with immune checkpoint inhibitor (ICI) treatment and radiation therapy in subjects with metastatic brain cancer. Subjects will be treated with the standard of care immunotherapy followed by radiation therapy via stereotactic radiosurgery at a reduced dose.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
  • Official Title: Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study

Clinical Trial IDs

  • ORG STUDY ID: RAON-IIR-IUSCC-0710
  • NCT ID: NCT04047602

Conditions

  • Brain Tumor
  • Brain Metastases
  • Brain Cancer

Purpose

This study will evaluate the rate of radiation necrosis following treatment with immune checkpoint inhibitor (ICI) treatment and radiation therapy in subjects with metastatic brain cancer. Subjects will be treated with the standard of care immunotherapy followed by radiation therapy via stereotactic radiosurgery at a reduced dose.

Detailed Description

      This is a prospective, single arm, pilot study to determine the symptomatic radiation
      necrosis rate at 6 months utilizing dose-reduced stereotactic radiosurgery with immunotherapy
      for subjects with a diagnosis of 1-10 brain metastases from MRI and tissue diagnosis of
      primary malignancy.

      Primary end-point is 6 month symptomatic radiation necrosis, defined as a 6-month rate of
      clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative
      intervention concomitant with advanced and routine brain imaging findings consistent with
      radiation necrosis. Follow-up MRIs will be fused with the planning scan for this assessment.
    

Trial Arms

NameTypeDescriptionInterventions
Reduced Dose Stereotactic RadiosugeryExperimentalSubjects will receive one SRS treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Brain MRI-confirmed 1-10 solid tumor brain metastases
    
              2. Biopsy-confirmed primary malignancy
    
              3. Diagnosis-specific graded prognostic assessment (DS-GPA) estimated median survival of
                 at least 6 months
    
              4. Stereotactic radiosurgery candidate per treating Radiation Oncologist
    
              5. ≥ 18 years old at the time of informed consent
    
              6. Ability to provide written informed consent and HIPAA (Health Insurance Portability
                 and Accountability Act) authorization. This will be assessed by the consenting
                 physician using general questions as outlined in Etchells' publication titled
                 Assessment of Patient Capacity to Consent to Treatment
    
              7. Absolute Lymphocyte Count > 800 units/microliter
    
              8. Patients currently on cytotoxic chemotherapy are eligible
    
              9. Patients receiving ICI up to 30 days prior to delivery of SRS
    
             10. Patients having undergone operative resection for metastatic brain disease within 30
                 days of immune checkpoint inhibitor (ICI) administration are eligible.
    
            Exclusion Criteria:
    
              1. Major medical illnesses or psychiatric impairments, which in the investigator's
                 opinion will prevent administration or completion of the protocol therapy and/or
                 interfere with follow-up
    
              2. Patients unable to receive MRI Brain
    
              3. Patients with more than 10 brain metastases on MRI Brain imaging
    
              4. Any lesion > 4 centimeter maximum diameter
    
              5. Total volume of metastatic disease more than 30 cubic centimeters
    
              6. Previous whole brain radiation therapy
    
              7. Previous stereotactic radiosurgery where the 50% isodose line overlaps with current
                 treatment field
    
              8. Already receiving chronic dexamethasone (chronic = > 2 weeks) prior to SRS
    
              9. Not a radiosurgical candidate per Radiation Oncology discretion
    
             10. Existing autoimmune disease
    
             11. Histology not amenable for SRS (i.e. lymphoma). (Small Cell Lung Cancer IS amenable.)
    
             12. Patients who have an unknown primary cancer
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Symptomatic radiation necrosis rate
    Time Frame:6 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis

    Secondary Outcome Measures

    Measure:Local control rate
    Time Frame:6 months, 12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume
    Measure:Radiographic radiation necrosis rate
    Time Frame:6 months, 12 months post SRS
    Safety Issue:
    Description:Defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emmission tomography (PET) imaging consistent with radiation necrosis.
    Measure:Symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis
    Measure:Gamma Knife local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who receive SRS via gamma knife techniques
    Measure:Linear accelerator local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who receive SRS via linear accelerator techniques
    Measure:Multi agent immune checkpoint inhibitor local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who are treated with multi-agent immune checkpoint inhibitor therapy.
    Measure:Single agent immune checkpoint inhibitor local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who are treated with single agent immune checkpoint inhibitor therapy.
    Measure:Melanoma brain metastases local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects with metastatic melanoma
    Measure:Non-melanoma brain metastases local control rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects with non melanoma metastatic disease
    Measure:Gamma knife symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects who receive SRS using gamma knife techniques
    Measure:Linear accelerator symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects who receive SRS using linear accelerator techniques
    Measure:Single agent immune checkpoint inhibitor symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects who are treated with single agent immune checkpoint inhibitor therapy
    Measure:Multi agent immune checkpoint inhibitor symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects who are treated with multi agent immune checkpoint inhibitor therapy
    Measure:Non melanoma brain metastases symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects with metastatic melanoma
    Measure:Melanoma brain metastases symptomatic radiation necrosis rate
    Time Frame:12 months post SRS
    Safety Issue:
    Description:Defined as the rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis in subjects with non melanoma metastatic disease

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Indiana University

    Trial Keywords

    • Radiation
    • Immune therapy
    • Stereotactic Radiosurgery

    Last Updated

    January 27, 2021