Brain TumorRADREMINCT04047602
Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
A study testing Reduced Dose SRS in people with Brain Tumor and Brain Metastases, run by Indiana University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumor, Brain Metastases, Brain Cancer
- What is being tested?
- Reduced Dose SRS
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- 12 Dec 2019to 20 Feb 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Indiana University Health Hospital
Indianapolis, Indiana, 46202
Indiana University Methodist Hospital
Indianapolis, Indiana, 46202
Oregon Health and Sciences
Portland, Oregon, 97239
About this study
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.
Read the 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
- Being tested
- Reduced Dose SRS
- Keywords
- Radiation, Immune therapy, Stereotactic Radiosurgery
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced Dose SRSRadiation
Subjects will receive SRS treatment at a reduced dose based on the brain tumor size
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Radiation: Reduced Dose SRS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (12)
Symptomatic Radiation Necrosis Rate
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. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 6 months
Symptomatic Radiation Necrosis Rate
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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Symptomatic Radiation Necrosis by SRS Group
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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Symptomatic Radiation Necrosis by Brain Metastases Group
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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group
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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of symptomatic radiation necrosis was calculated. Ppatients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Local Control
Local control was 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. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired.
Measured: 6 months
Local Control
Local control was 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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Local Control by SRS Group
Local control was 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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Local Control by Brain Metastases Group
Local control was 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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Local Control by Immune Checkpoint Inhibitor (ICI) Group
Local control was 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. This measure details the estimated 12-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to local failure was calculated. Patients who did not experience local failure were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Radiographic Radiation Necrosis Rate
Radiographic radiation necrosis was 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. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 6 months
Radiographic Radiation Necrosis Rate
Radiographic radiation necrosis was 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. This measure details the estimated 6-month survival and associated 95% confidence interval from the Kaplan Meier method. The time from treatment start to the presence of radiographic radiation necrosis was calculated. Patients who did not experience the outcome were censored at the date last known alive or at the date of death if they expired.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start12 Dec 2019
- Primary completion25 Jul 2023
- Study completion20 Feb 2024
Why it stopped: trial stopped due to low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain TumorStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Shiue, MD, Indiana University
- Investigators
- Kevin Shiue, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04047602
- Sponsor's protocol ID
- RAON-IIR-IUSCC-0710
- Acronym
- RADREMI
- Status last verified
- Jan 2025
- First submitted
- 5 Aug 2019
- Last updated
- 13 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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.
PubMed 32477016
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
- ClinicalTrials.gov ID
- NCT04047602
- Acronym / sponsor ID
- RADREMI / RAON-IIR-IUSCC-0710
- Conditions
- Brain Tumor, Brain Metastases, Brain Cancer
- Keywords
- Radiation, Immune therapy, Stereotactic Radiosurgery
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: trial stopped due to low accrual
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 12 Dec 2019 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 20 Feb 2024 (actual)
- First posted
- 7 Aug 2019 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reduced Dose Stereotactic Radiosurgery | Experimental | Radiation: Reduced Dose SRSSubjects 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced Dose SRSSubjects will receive SRS treatment at a reduced dose based on the brain tumor size | Radiation | Reduced Dose Stereotactic Radiosurgery |
Primary outcome
Symptomatic Radiation Necrosis Proportion
Time frame: 6 months
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.
12 secondary outcomes
Symptomatic Radiation Necrosis Rate
Time frame: 6 months
Symptomatic Radiation Necrosis Rate
Time frame: 12 months
Symptomatic Radiation Necrosis by SRS Group
Time frame: 12 months
Symptomatic Radiation Necrosis by Brain Metastases Group
Time frame: 12 months
Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group
Time frame: 12 months
Local Control
Time frame: 6 months
Local Control
Time frame: 12 months
Local Control by SRS Group
Time frame: 12 months
Local Control by Brain Metastases Group
Time frame: 12 months
Local Control by Immune Checkpoint Inhibitor (ICI) Group
Time frame: 12 months
Radiographic Radiation Necrosis Rate
Time frame: 6 months
Radiographic Radiation Necrosis Rate
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32477016McClelland 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Shiue, MD principal investigator
Indiana University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reduced Dose SRS in people with Brain Tumor and Brain Metastases, run by Indiana University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptomatic Radiation Necrosis Proportion (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04047602, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025; AzTrials last refreshed its copy on 6 Nov 2026.