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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Brain Tumor, Brain Metastases, Brain Cancer

Intervention / Treatment
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* Radiation: Reduced Dose SRS


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Dose Stereotactic Radiosurgery<br>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 | Radiation: Reduced Dose SRS<br>* Subjects will receive SRS treatment at a reduced dose based on the brain tumor size<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months post SRS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months, 12 months post SRS | 
| 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. | 6 months, 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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. | 12 months post SRS | 
| 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. | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 
| 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 | 12 months post SRS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation, Immune therapy, Stereotactic Radiosurgery