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

Not Applicable

Completed

• Conditions: Brain Metastases; Brain Tumor; Brain Cancer
• Interventions: Radiation: Reduced Dose SRS

• Registration Number: NCT04047602
• Lead Sponsor: Indiana University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-08-05
• Study First Submitted QC: 2019-08-05
• Study First Posted: 2019-08-07
• Study Start: 2019-12-12
• Primary Completion: 2023-07-25
• Study Completion: 2024-02-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-11
• Last Update Posted: 2024-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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.

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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.)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Reduced Dose Stereotactic Radiosurgery	Reduced Dose SRS	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

Primary Outcome Measures

Name	Time	Method
Six-Month Symptomatic Radiation Necrosis Proportion	6 months post SRS	The observed proportion of evaluable patients with symptomatic radiation necrosis by 6-months. Symptomatic radiation necrosis was 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

Name	Time	Method
Local Control Rate	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	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 emission tomography (PET) imaging consistent with radiation necrosis.
Symptomatic Radiation Necrosis Rate	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	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	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	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	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	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	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	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	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	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	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	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	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

Trial Locations

Locations (3)

Indiana University Health Hospital; 🇺🇸 Indianapolis, Indiana, United States

Indiana University Methodist Hospital; 🇺🇸 Indianapolis, Indiana, United States

Oregon Health and Sciences; 🇺🇸 Portland, Oregon, United States