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

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ClinicalTrials.gov Identifier: NCT04047602
Recruitment Status : Recruiting
First Posted : August 7, 2019
Last Update Posted : September 24, 2020
Sponsor:
Information provided by (Responsible Party):
Gordon A Watson, MD/PhD, Indiana University

Tracking Information
First Submitted Date  ICMJE August 5, 2019
First Posted Date  ICMJE August 7, 2019
Last Update Posted Date September 24, 2020
Actual Study Start Date  ICMJE August 21, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
Symptomatic radiation necrosis rate [ Time Frame: 6 months post SRS ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Local control rate [ Time Frame: 6 months, 12 months post SRS ]
    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
  • Radiographic radiation necrosis rate [ Time Frame: 6 months, 12 months post SRS ]
    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.
  • Symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Gamma Knife local control rate [ Time Frame: 12 months post SRS ]
    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
  • Linear accelerator local control rate [ Time Frame: 12 months post SRS ]
    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
  • Multi agent immune checkpoint inhibitor local control rate [ Time Frame: 12 months post SRS ]
    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.
  • Single agent immune checkpoint inhibitor local control rate [ Time Frame: 12 months post SRS ]
    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.
  • Melanoma brain metastases local control rate [ Time Frame: 12 months post SRS ]
    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
  • Non-melanoma brain metastases local control rate [ Time Frame: 12 months post SRS ]
    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
  • Gamma knife symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Linear accelerator symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Single agent immune checkpoint inhibitor symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Multi agent immune checkpoint inhibitor symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Non melanoma brain metastases symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
  • Melanoma brain metastases symptomatic radiation necrosis rate [ Time Frame: 12 months post SRS ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Official Title  ICMJE Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor
  • Brain Metastases
  • Brain Cancer
Intervention  ICMJE Radiation: Reduced Dose SRS
Subjects will receive SRS treatment at a reduced dose based on the brain tumor size
Study Arms  ICMJE Experimental: Reduced Dose Stereotactic Radiosugery
Subjects 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, 2, 6, 9, and 12 months post SRS treatment
Intervention: Radiation: Reduced Dose SRS
Publications * McClelland S 3rd, Lautenschlaeger T, Zang Y, Hanna NH, Shiue K, Kamer AP, Agrawal N, Ellsworth SG, Rhome RM, Watson GA. Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol. Rep Pract Oncol Radiother. 2020 Jul-Aug;25(4):500-506. doi: 10.1016/j.rpor.2020.04.007. Epub 2020 Apr 23. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2019)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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. small cell lung cancer, lymphoma)
  12. Patients who have an unknown primary cancer
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathryn Lauer 317-962-3172 KLauer@iuhealth.org
Contact: Amy Miller amym@iu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04047602
Other Study ID Numbers  ICMJE RAON-IIR-IUSCC-0710
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gordon A Watson, MD/PhD, Indiana University
Study Sponsor  ICMJE Indiana University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kevin R. Shiue, MD Indiana University
PRS Account Indiana University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP