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

Primary Purpose

Brain Tumor, Brain Metastases, Brain Cancer

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Reduced Dose SRS
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Tumor focused on measuring Radiation, Immune therapy, Stereotactic Radiosurgery

Eligibility Criteria

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

Inclusion Criteria:

  1. Brain MRI-confirmed 1-10 solid tumor brain metastases
  2. Biopsy-confirmed primary malignancy
  3. ds-GPA estimated median survival of at least 6 months, for histologies not included in the ds-GPA, publications or noted online at brainmetgpa.com, the PI will use either published or validated data or their best clinical judgment to determine the patient's expected survival
  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.
  7. ALC > 800/ul (Ku et al., 2010)
  8. Patients currently on cytotoxic chemotherapy are eligible
  9. Patients receiving ICI up to 30 days prior to delivery of SRS are eligible
  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. For Cohort 1: Previous stereotactic radiosurgery where the 50% isodose line overlaps with current treatment field
  8. For Cohort 2: Patients whose treatment will have a dose overlap within the target from prior treatments of 20% or greater
  9. Already receiving chronic dexamethasone (chronic = > 2 weeks) prior to SRS
  10. Not a radiosurgical candidate per Radiation Oncology discretion
  11. Existing autoimmune disease
  12. Patients who have an unknown primary cancer
  13. Histology not amenable for SRS (i.e. lymphoma). (Small Cell Lung Cancer IS amenable.)

Sites / Locations

  • Indiana University Health HospitalRecruiting
  • Indiana University Methodist HospitalRecruiting
  • Oregon Health and Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reduced Dose Stereotactic Radiosurgery

Arm Description

Subjects will receive one stereotactic radiosurgery (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

Outcomes

Primary Outcome Measures

Symptomatic radiation necrosis rate
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

Local control rate
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
Defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis.
Symptomatic radiation necrosis rate
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
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
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
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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
August 5, 2019
Last Updated
May 4, 2023
Sponsor
Indiana University
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1. Study Identification

Unique Protocol Identification Number
NCT04047602
Brief Title
Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Acronym
RADREMI
Official Title
Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 12, 2019 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Tumor, Brain Metastases, Brain Cancer
Keywords
Radiation, Immune therapy, Stereotactic Radiosurgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Reduced Dose Stereotactic Radiosurgery
Arm Type
Experimental
Arm Description
Subjects will receive one stereotactic radiosurgery (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
Intervention Type
Radiation
Intervention Name(s)
Reduced Dose SRS
Intervention Description
Subjects will receive SRS treatment at a reduced dose based on the brain tumor size
Primary Outcome Measure Information:
Title
Symptomatic radiation necrosis rate
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
Time Frame
6 months post SRS
Secondary Outcome Measure Information:
Title
Local control rate
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
Time Frame
6 months, 12 months post SRS
Title
Radiographic radiation necrosis rate
Description
Defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis.
Time Frame
6 months, 12 months post SRS
Title
Symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Gamma Knife local control rate
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
Time Frame
12 months post SRS
Title
Linear accelerator local control rate
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
Time Frame
12 months post SRS
Title
Multi agent immune checkpoint inhibitor local control rate
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.
Time Frame
12 months post SRS
Title
Single agent immune checkpoint inhibitor local control rate
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.
Time Frame
12 months post SRS
Title
Melanoma brain metastases local control rate
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
Time Frame
12 months post SRS
Title
Non-melanoma brain metastases local control rate
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
Time Frame
12 months post SRS
Title
Gamma knife symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Linear accelerator symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Single agent immune checkpoint inhibitor symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Multi agent immune checkpoint inhibitor symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Non melanoma brain metastases symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS
Title
Melanoma brain metastases symptomatic radiation necrosis rate
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
Time Frame
12 months post SRS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Brain MRI-confirmed 1-10 solid tumor brain metastases Biopsy-confirmed primary malignancy ds-GPA estimated median survival of at least 6 months, for histologies not included in the ds-GPA, publications or noted online at brainmetgpa.com, the PI will use either published or validated data or their best clinical judgment to determine the patient's expected survival Stereotactic radiosurgery candidate per treating Radiation Oncologist ≥ 18 years old at the time of informed consent Ability to provide written informed consent and HIPAA (Health Insurance Portability and Accountability Act) authorization. ALC > 800/ul (Ku et al., 2010) Patients currently on cytotoxic chemotherapy are eligible Patients receiving ICI up to 30 days prior to delivery of SRS are eligible Patients having undergone operative resection for metastatic brain disease within 30 days of immune checkpoint inhibitor (ICI) administration are eligible. Exclusion Criteria: 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 Patients unable to receive MRI Brain Patients with more than 10 brain metastases on MRI Brain imaging Any lesion > 4 centimeter maximum diameter Total volume of metastatic disease more than 30 cubic centimeters Previous whole brain radiation therapy For Cohort 1: Previous stereotactic radiosurgery where the 50% isodose line overlaps with current treatment field For Cohort 2: Patients whose treatment will have a dose overlap within the target from prior treatments of 20% or greater Already receiving chronic dexamethasone (chronic = > 2 weeks) prior to SRS Not a radiosurgical candidate per Radiation Oncology discretion Existing autoimmune disease Patients who have an unknown primary cancer Histology not amenable for SRS (i.e. lymphoma). (Small Cell Lung Cancer IS amenable.)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn Lauer
Phone
317-962-3172
Email
KLauer@iuhealth.org
First Name & Middle Initial & Last Name or Official Title & Degree
Nikki Barrow
Email
nrbarrow@iu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Shiue, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Health Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikki Barrow
Email
nrbarrow@iu.edu
First Name & Middle Initial & Last Name & Degree
Ryan Rhome, MD,PhD
First Name & Middle Initial & Last Name & Degree
Nasser Hanna, MD
Facility Name
Indiana University Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Lauer
Phone
317-962-3172
Email
KLauer@iuhealth.org
First Name & Middle Initial & Last Name & Degree
Ryan Rhome, MD, PhD
Facility Name
Oregon Health and Sciences
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Completed

12. IPD Sharing Statement

Citations:
PubMed Identifier
32477016
Citation
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.
Results Reference
derived

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

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