Brain MetastasesPhase 2NCT02747303
Frameless Stereotactic Radiosurgery for Intact Brain Metastases
A Phase 2 study testing Stereotactic Radiosurgery in people with Brain Metastases, run by University of Chicago at 1 site in United States.
Trial summary
This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- Stereotactic Radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Sep 2023to 22 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more.
- Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-5 intraparenchymal brain metastases.
- Well-circumscribed, measureable intraparenchymal brain lesion(s) with maximum tumor diameter ≤3.0 cm. If multiple lesions are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one lesion must be ≥1.0 cm in maximum diameter and ≥0.5 cm in a perpendicular diameter to be considered measurable disease.
- Negative urine or serum pregnancy test done ≤ 14 days prior to CT simulation, for women of child-bearing potential only.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Diagnosis of germ cell tumor, small cell carcinoma or hematologic malignancy.
- Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts).
- Diagnosis of leptomeningeal disease.
- Prior cranial radiotherapy within 90 days of trial enrollment or prior SRS at any time to any lesion to be treated on protocol
- Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS. Hormonal therapy is permitted. For Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS. Patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled.
- Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR<30, gadolinium allergy).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Chicago
Chicago, Illinois, 60637
Robyn Hseu, rhseu@radonc.uchicago.edu
Aditya Juloori, M.D., Ph.D.
About this study
Official title: The Clinical Relevance of Margins in Frameless Stereotactic Radiosurgery for Intact Brain Metastases: a Randomized Trial of 0 vs 2 mm Margins
This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases.
- Conditions
- Brain Metastases
- Being tested
- Stereotactic Radiosurgery
- Keywords
- brain metastases, 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.
Stereotactic RadiosurgeryProcedure or surgery
The SRS dose will depend on the maximum diameter of the gross tumor volume (GTV)
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Radiosurgery to 2 mm GTV to PTV margins | Active comparator | Not described Receives: Procedure: Stereotactic Radiosurgery |
| Stereotactic Radiosurgery to 0 mm GTV to PTV margins | Experimental | Not described Receives: Procedure: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) rates estimated by the Kaplan-Meier method at 6 months
Progression free survival (PFS) rates will be estimated by the Kaplan-Meier method and the 0-mm and 2-mm groups will be compared via the log-rank statistic with a one-sided test of significance, using follow-up data up to 6 months.
Measured: 6 months
Secondary outcomes (10)
Progression free survival (PFS) rates estimated by the Kaplan-Meier method
Progression free survival (PFS) rates will be estimated by the Kaplan-Meier method and the 0-mm, and 2-mm groups will be compared via the log-rank statistic with a one-sided test of significance, using follow-up data up to 6 months.
Measured: 2 years
Overall survival rates
Time from Stereotactic Radiosurgery (SRS) completion to death.
Measured: 2 years
Rates of radiation necrosis
To evaluate the superiority of frameless LINAC-based SRS using 0 mm margins compared to 2 mm margins in reducing rates of radiation necrosis.
Measured: 2 years
Rates of pseudoprogression
To evaluate the superiority of frameless LINAC-based SRS using 0 mm margins compared to 2 mm margins in reducing rates of radiation pseudoprogression.
Measured: 2 years
Local failure rates
Local failure and OS rates at 6 months, 1 year and 2 years will be estimated by the Kaplan-Meier method, comparing arms via the log-rank statistic.
Measured: 2 years
Rate of acute central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities
Any acute CTCAE v4.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).
Measured: 90 days
Rate of late central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities
To compare rates of late (greater than 90 days from SRS) CTCAE v4.0 CNS Grade 2+ and Grade 3+ toxicities.
Measured: 2 years
Rates of distant intracranial failure
The appearance of new non-target lesions ≥5 mm following completion of radiotherapy will be considered distant intracranial failure. If a non-target lesion <5 mm is found on a later scan to have increased to ≥ 5 mm, distant intracranial failure will be declared at the date of the earliest scan showing the new lesion.
Measured: 2 years
Rates of salvage therapy
Time to initiation of any combination of salvage Stereotactic Radiosurgery (SRS), Whole Brain Radiation Therapy WBRT, or neurosurgical resection for intracranial failure.
Measured: 2 years
Association between dose and risk of radionecrosis or pseudoprogression
To determine association between V10Gy and V12Gy all tissue, whole brain and normal brain parameters and risk of radionecrosis or pseudoprogression.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2016 (estimated)
- Study start5 Sep 2023
- Primary completion22 Aug 2028 (estimated)
- Study completion22 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 166 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven J. Chmura, M.D., Ph.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02747303
- Sponsor's protocol ID
- IRB15-1476
- Status last verified
- Sep 2026
- First submitted
- 19 Apr 2016
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Relevance of Margins in Frameless Stereotactic Radiosurgery for Intact Brain Metastases: a Randomized Trial of 0 vs 2 mm Margins
- ClinicalTrials.gov ID
- NCT02747303
- Acronym / sponsor ID
- IRB15-1476
- Conditions
- Brain Metastases
- Keywords
- brain metastases, Stereotactic Radiosurgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 166 participants (estimated)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 5 Sep 2023 (actual)
- Primary completion
- 22 Aug 2028 (estimated)
- Study completion
- 22 Aug 2028 (estimated)
- First posted
- 21 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized study to determine if not treating planning target volume (PTV) margins during radiation therapy worsens progression free survival rates in patients with brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Radiosurgery to 2 mm GTV to PTV margins | Active comparator | Procedure: Stereotactic Radiosurgery |
| Stereotactic Radiosurgery to 0 mm GTV to PTV margins | Experimental | Procedure: Stereotactic Radiosurgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more.
- Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-5 intraparenchymal brain metastases.
- Well-circumscribed, measureable intraparenchymal brain lesion(s) with maximum tumor diameter ≤3.0 cm. If multiple lesions are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one lesion must be ≥1.0 cm in maximum diameter and ≥0.5 cm in a perpendicular diameter to be considered measurable disease.
- Negative urine or serum pregnancy test done ≤ 14 days prior to CT simulation, for women of child-bearing potential only.
- Ability to understand and willingness to sign a written informed consent document.
Key exclusion criteria (6 listed)
- Diagnosis of germ cell tumor, small cell carcinoma or hematologic malignancy.
- Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts).
- Diagnosis of leptomeningeal disease.
- Prior cranial radiotherapy within 90 days of trial enrollment or prior SRS at any time to any lesion to be treated on protocol
- Chemotherapy (including oral agents and targeted agents) or immunotherapy given within 14 days of SRS. Hormonal therapy is permitted. For Her2+ breast cancer patients, anti-Her2 therapy cannot be given within 14 days of SRS. Patients who are scheduled to receive trastuzumab emtansine after SRS cannot be enrolled.
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 |
|---|---|---|
| Stereotactic RadiosurgeryThe SRS dose will depend on the maximum diameter of the gross tumor volume (GTV) | Procedure or surgery | Stereotactic Radiosurgery to 0 mm GTV to PTV margins, Stereotactic Radiosurgery to 2 mm GTV to PTV margins |
Primary outcome
Progression free survival (PFS) rates estimated by the Kaplan-Meier method at 6 months
Time frame: 6 months
Progression free survival (PFS) rates will be estimated by the Kaplan-Meier method and the 0-mm and 2-mm groups will be compared via the log-rank statistic with a one-sided test of significance, using follow-up data up to 6 months.
10 secondary outcomes
Progression free survival (PFS) rates estimated by the Kaplan-Meier method
Time frame: 2 years
Overall survival rates
Time frame: 2 years
Rates of radiation necrosis
Time frame: 2 years
Rates of pseudoprogression
Time frame: 2 years
Local failure rates
Time frame: 2 years
Rate of acute central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities
Time frame: 90 days
Rate of late central nervous system (CNS) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and higher toxicities
Time frame: 2 years
Rates of distant intracranial failure
Time frame: 2 years
Rates of salvage therapy
Time frame: 2 years
Association between dose and risk of radionecrosis or pseudoprogression
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
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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.
Steven J. Chmura, M.D., Ph.D. principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Radiosurgery in people with Brain Metastases, run by University of Chicago at 1 site 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 5 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Robyn Hseu (773-834-3198, rhseu@radonc.uchicago.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) rates estimated by the Kaplan-Meier method at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2026.