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

NCT ID: NCT04047602

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-12
• Study Completion Date: 2024-02-20

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.

Conditions

Brain Tumor; Brain Metastases; Brain Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Reduced Dose Stereotactic Radiosurgery

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

Group Type: EXPERIMENTAL

Reduced Dose SRS

Intervention Type: RADIATION

Subjects will receive SRS treatment at a reduced dose based on the brain tumor size

Interventions

Reduced Dose SRS

Subjects will receive SRS treatment at a reduced dose based on the brain tumor size

Intervention Type: RADIATION

Eligibility Criteria

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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Kevin Shiue, MD

Associate Professor of Clinical Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin Shiue, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University Health Hospital

Indianapolis, Indiana, United States

Indiana University Methodist Hospital

Indianapolis, Indiana, United States

Oregon Health and Sciences

Portland, Oregon, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32477016 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RAON-IIR-IUSCC-0710

Identifier Type: -

Identifier Source: org_study_id