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

NCT04047602 | Terminated Results DMC FDA Device

• 1 other identifier: RAON-IIR-IUSCC-0710
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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.

Conditions

Brain Tumor; Brain Metastases; Brain Cancer

Keywords

Radiation; Immune therapy; Stereotactic Radiosurgery

Outcome Measures

Primary Outcomes (1)

• Symptomatic Radiation Necrosis Proportion

  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.

  6 months

Secondary Outcomes (12)

• Symptomatic Radiation Necrosis Rate

  6 months

• Symptomatic Radiation Necrosis Rate

  12 months

• Symptomatic Radiation Necrosis by SRS Group

  12 months

• Symptomatic Radiation Necrosis by Brain Metastases Group

  12 months

• Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group

  12 months

Study Arms (1)

Reduced Dose Stereotactic Radiosurgery

EXPERIMENTAL

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

Interventions

Reduced Dose SRS RADIATION

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

Reduced Dose Stereotactic Radiosurgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Indiana University: lead

Study Sites (3)

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Oregon Health and Sciences

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• 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.

  PMID: 32477016 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Kevin Shiue, MD
• Organization: Indiana University Health

kshiue@iuhealth.org

317 944 2524

Study Officials

• Kevin Shiue, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Radiation Oncology

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 7, 2019
• Study Start: December 12, 2019
• Primary Completion: July 25, 2023
• Study Completion: February 20, 2024
• Last Updated: February 13, 2025
• Results First Posted: September 19, 2024

Record last verified: 2025-01

Locations

US (3)