Brain MetastasesNCT06857006
Trial of Differential Margins in Single Isocenter Radiosurgery of Brain Metastases
A study testing brain metastases radiosurgery in people with Brain Metastases, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Radiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- brain metastases radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2025to Aug 2028
- Phase
- Interventional
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 19 and older
- Brain metastases diagnosis not requiring retreatment to the same tumor
- For females of reproductive potential should undergo pregnancy testing as per UAB Radiation Oncology standard policies
- Ability of subject or Legally Authorized Representative (LAR)) to understand and the willingness to sign a written informed consent document.
Who cannot join
- Current use of cytotoxic chemotherapy within 3 days of treatment. There are no restrictions on the use of immunotherapy during treatment. TKIs known to be radiation sensitizers such as BRAF should be held at least 24 hours prior to treatment.
- Inability to have MRI imaging
- Pregnancy
- Treatment with another investigational drug 14 days of enrollment
- Radiosurgery planned for post-operative adjuvant cavity only. Patients with any gross residual after surgery are eligible. Patients with at least one intact metastasis may enroll but adjuvant cavity will not be evaluable.
- At the time of Radiation Oncology consultation more than twenty targets are identified. Note that it is common that a few additional metastases may be identified during the treatment planning or peer review processes. More than twenty targets may be included if this number is found after the initial clinical review of the treatment planning MRI.
Show all 10Show fewer
- Tumor maximal diameter > 4 cm.
- Prior SBRT or SRS to a lesion planned for retreatment. Note that patients with prior whole brain radiation alone are eligible.
- Patients with diffuse leptomeningeal tumor are not eligible. Patients with a focal dural or pachymeningeal tumor are eligible if other intra-axial tumors are planned to be treated. Similar to postoperative cavities, the pachymeningeal tumor deposit will be treated but not evaluable for the assessment of local control or toxicity.
- INCLUSION OF VULNERABLE PARTICIPANTS Vulnerable populations as defined by the NIH including children, prisoners, and adult subjects who lack capacity to consent to research participation are not eligible.
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 Alabama at Birmingham (UAB) Hazelrig-Salter Radiation Oncology Center
Birmingham, Alabama, 35249
John Fiveash, MD
Richard Popple, MD
About this study
Official title: UAB 2507 - Randomized Phase II Study of Differential Margins in Single Isocenter Radiosurgery of Brain Metastases
Radiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment.
Read the detailed description
Without a stereotactic frame there is considerable variation in practice in the use of planning target volume (PTV) margins for linac radiosurgery. In particular, the use of a single isocenter for multiple targets geometrically increases the risk that rotational errors will result in significant dosimetric errors, and many centers have considered adding margin. A recent AAPM task group survey has found that ~90% of centers worldwide add a PTV margin to account for error and that 8% add more than 2 mm. The most common margin is 2 mm. Other potential reasons to add a margin include spacial MRI error, couch walkout, CBCT to linac isocenter mismatch, and undetected intrafraction motion. Treatment volume is the greatest predictor of radiation toxicity associated with radiosurgery and potentially unnecessary margins will lead to increased risk to the patient. This trial will incorporate a composite endpoint that includes control of the tumor and toxicity.
Uncomplicated tumor control probability (UTCP) is defined as the chance the tumor is locally controlled (TCP) without grade 3 or greater CNS toxicity (1-NTCP). The investigators hypothesize a 2 mm margin will worsen uncomplicated control compared to a 0 mm PTV margin in the treatment multiple metastases in a single fraction.
This trial will inform the standard of care margin (0 mm vs 2 mm) for single isocenter treatment of multiple targets.
- Conditions
- Brain Metastases
- Being tested
- brain metastases radiosurgery
- Keywords
- Brain Metastases, stereotactic radiosurgery (SRS), radiosurgery (RS), edge linear accelerator, single isocenter 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.
brain metastases radiosurgeryProcedure or surgery
Radiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment.
| Study group | Role | What they receive |
|---|---|---|
| 0mm margin | Active comparator | For each patient two radiation treatment plans will be created. One will have 0 mm margin for the planning target volume.
Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance:
< 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy. Receives: Procedure: brain metastases radiosurgery |
| 2mm margin | Active comparator | For each patient two radiation treatment plans will be created. One will be 2 mm margin for the planning target volume.
Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance:
< 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy. Receives: Procedure: brain metastases radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference between 0mm and 2mm
Fisher's Exact Test to determine if (per patient) uncomplicated control is improved or worsened with the addition of a 2mm PTV margin in the treatment of brain metastases with single isocenter radiosurgery.
Measured: 12 months
Secondary outcomes (3)
Maximum margin size of the tumor
To compare 0mm margin and 2mm margin radiosurgery for local tumor control, RANO assessment by individual tumor calculated by multiplying the longest diameter on an axial slice and its longest perpendicular diameter on the same slice
Measured: 12 months
Percentage of toxicity
To compare 0mm margin and 2mm margin radiosurgery for toxicity. NTCP - assessed per tumor and per patient, assign to all tumors if attribution ambiguous (only grade 3 or greater CNS toxicity included)
Measured: 12 months
Change in normal brain dosimetry
To compare 0mm margin and 2mm margin radiosurgery for normal brain dosimetry.
- Dosimetry of normal brain (2 mm vs 0 mm)
- Dosimetry of hippocampi (2 mm vs 0 mm)
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 posted4 Mar 2025
- Study start8 Apr 2025
- Primary completionJun 2028 (estimated)
- Study completionAug 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 Alabama at BirminghamThe 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
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Fiveash, MD, University of Alabama at Birmingham
- Investigators
- John A Fiveash, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06857006
- Sponsor's protocol ID
- IRB-300014291 (UAB2507)
- Other IDs
- Robert Award
- Status last verified
- Jul 2026
- First submitted
- 26 Feb 2025
- Last updated
- 30 Jul 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 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- UAB 2507 - Randomized Phase II Study of Differential Margins in Single Isocenter Radiosurgery of Brain Metastases
- ClinicalTrials.gov ID
- NCT06857006
- Acronym / sponsor ID
- IRB-300014291 (UAB2507)
- Conditions
- Brain Metastases
- Keywords
- Brain Metastases, stereotactic radiosurgery (SRS), radiosurgery (RS), edge linear accelerator, single isocenter radiosurgery
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 8 Apr 2025 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 4 Mar 2025 (actual)
- 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.
Radiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment.
Detailed description
Without a stereotactic frame there is considerable variation in practice in the use of planning target volume (PTV) margins for linac radiosurgery. In particular, the use of a single isocenter for multiple targets geometrically increases the risk that rotational errors will result in significant dosimetric errors, and many centers have considered adding margin. A recent AAPM task group survey has found that ~90% of centers worldwide add a PTV margin to account for error and that 8% add more than 2 mm. The most common margin is 2 mm. Other potential reasons to add a margin include spacial MRI error, couch walkout, CBCT to linac isocenter mismatch, and undetected intrafraction motion. Treatment volume is the greatest predictor of radiation toxicity associated with radiosurgery and potentially unnecessary margins will lead to increased risk to the patient. This trial will incorporate a composite endpoint that includes control of the tumor and toxicity.
Uncomplicated tumor control probability (UTCP) is defined as the chance the tumor is locally controlled (TCP) without grade 3 or greater CNS toxicity (1-NTCP). The investigators hypothesize a 2 mm margin will worsen uncomplicated control compared to a 0 mm PTV margin in the treatment multiple metastases in a single fraction.
This trial will inform the standard of care margin (0 mm vs 2 mm) for single isocenter treatment of multiple targets.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0mm margin | Active comparator | Procedure: brain metastases radiosurgeryFor each patient two radiation treatment plans will be created. One will have 0 mm margin for the planning target volume. Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance: < 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy. |
| 2mm margin | Active comparator | Procedure: brain metastases radiosurgeryFor each patient two radiation treatment plans will be created. One will be 2 mm margin for the planning target volume. Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance: < 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 19 and older
- Brain metastases diagnosis not requiring retreatment to the same tumor
- For females of reproductive potential should undergo pregnancy testing as per UAB Radiation Oncology standard policies
- Ability of subject or Legally Authorized Representative (LAR)) to understand and the willingness to sign a written informed consent document.
Key exclusion criteria (10 listed)
- Current use of cytotoxic chemotherapy within 3 days of treatment. There are no restrictions on the use of immunotherapy during treatment. TKIs known to be radiation sensitizers such as BRAF should be held at least 24 hours prior to treatment.
- Inability to have MRI imaging
- Pregnancy
- Treatment with another investigational drug 14 days of enrollment
- Radiosurgery planned for post-operative adjuvant cavity only. Patients with any gross residual after surgery are eligible. Patients with at least one intact metastasis may enroll but adjuvant cavity will not be evaluable.
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 |
|---|---|---|
| brain metastases radiosurgeryRadiosurgery is the use of a focal high dose of radiation therapy to ablate or kill a tumor. This trial will enroll patients with brain metastases 4 cm or less in greatest diameter and will compare 0mm margin to a 2mm margin for treatment. | Procedure or surgery | 0mm margin, 2mm margin |
Primary outcome
Difference between 0mm and 2mm
Time frame: 12 months
Fisher's Exact Test to determine if (per patient) uncomplicated control is improved or worsened with the addition of a 2mm PTV margin in the treatment of brain metastases with single isocenter radiosurgery.
3 secondary outcomes
Maximum margin size of the tumor
Time frame: 12 months
Percentage of toxicity
Time frame: 12 months
Change in normal brain dosimetry
Time frame: 12 months
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 30 Jul 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.
John A Fiveash, MD principal investigator
The University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing brain metastases radiosurgery in people with Brain Metastases, run by University of Alabama at Birmingham 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 10 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 30 Jul 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.
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 John Fiveash, MD (205-975-0224, jfiveash@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference between 0mm and 2mm (time frame: 12 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 30 Jul 2026.