Brain Neoplasms, Adult, MalignantSRSNCT02645487
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis
A study testing Stereotactic Radiosurgery in people with Brain Neoplasms, Adult, Malignant, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Neoplasms, Adult, Malignant
- 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
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2015to 23 Dec 2026
- 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
- Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
- Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
- All brain metastases must be outside the brain stem (midbrain, pons and medulla).
- Patient must have 10 or less brain metastases.
- The maximum diameter of any lesion must be less than or equal to 3.0 cm.
- Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
Show all 15Show fewer
- Radiation was not to the brain.
- Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
- Age ≥ 18 years.
- ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
- All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Ability to understand and the willingness to sign a written informed consent.
Who cannot join
- Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
- Patients with leptomeningeal metastasis.
- NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
- Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
- Patients with life expectancy < 3 months.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: A Phase I Dose-Escalation Study of Stereotactic Radiosurgery for Brain Metastasis Without Whole Brain Radiation
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Read the detailed description
Recently, several large randomized studies have shown that in patients with limited brain metastases, whole brain radiation can be safely deferred when treated with SRS and close surveillance. In light of this, most of such patients are now treated with SRS alone without WBRT. However, the SRS doses set by Radiation Therapy Oncology Group (RTOG) 90-05 continue to be applied to patients without previous cranial irradiation.
The potential insufficiency of current SRS dose for long-term tumor control is of pressing concern. The advances chemotherapy has led to an improvement in overall survival in many patients with metastatic cancer, including malignancies often associated with brain metastases, such as lung (40-50%) and breast (15%). As these patients survive longer, more patients may develop brain metastases and the current dose of SRS may not be adequate to control the brain metastases for the duration of their survival. In fact, there is evidence that the control rate declines with time after SRS, and after 3 years, the local control rate may be only about 60%. In the case of brain metastases from relatively radio-resistant melanoma, the reported 12-months local control rates for SRS range from 52% to 75%. More potent SRS doses could lead to improved long-term control of brain metastases.
- Conditions
- Brain Neoplasms, Adult, Malignant
- Being tested
- 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 RadiosurgeryRadiation
Also called SRS
Radiation, Stereotactic Radiosurgery Size <= 1cm: 24 Gray (Gy); + 3 Gy incremental escalation up to 30 Gy >1-2cm: 21 Gy; + 3 Gy incremental escalation up to 27 Gy >2-3cm: 18 Gy; + 3 Gy incremental escalation up to 24 Gy
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | Radiation, Stereotactic Radiosurgery Dose-Escalation Receives: Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Tolerated Doses
The maximal tolerated doses for single-fraction stereotactic radiosurgery, within 90 days from the date of procedure, in patients with brain metastases who have not undergone prior brain irradiation was determined according to the following conditions: if zero or one out of the first seven, two or fewer out of the first nine, three or fewer out of the first twelve, or four or fewer out of the first fifteen of patients within 3-month follow-up experience a dose-limiting toxicity (DLT) as defined in the study protocol, then the dose was escalated to the next dose level according to principal investigator discretion. If three or more of the first nine patients, four or more of the first twelve, or five or more of the first fifteen patients experienced a DLT, then the maximum tolerated dose (MTD) was considered to have been exceeded. Each cohort had 3 maximum dose levels that could be met by reaching the dose escalation conditions.
Measured: 90 days
Secondary outcomes (4)
Overall Survival
To evaluate the overall survival (OS), which is defined as the time between date of SRS and the date of death due to any cause.
Measured: 3 years
Time to Progression
To evaluate time to progression (TTP), which is defined as the time between date of SRS and date of documented progression. Specific TTP will be determined for the target lesion, non-target lesions, and elsewhere in brain.
Measured: 3 years
Local Progression Rate
To evaluate the local progression rate of the target lesion. Local progression will be defined by MRI (with or without contrast)/CT (with contrast) imaging according to the modified RECIST 1.1 criteria. Suspected radiation necrosis and/or pseudoprogression will be similarly evaluated
Measured: 3 years
Response Rate
To evaluate the response rate, consisting of complete response (CR) and partial response according to the modified RECIST 1.1.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2016 (estimated)
- Study start18 Dec 2015
- Primary completion23 Mar 2025
- Study completion23 Dec 2026 (estimated)
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.
- Other trials for Brain Neoplasms, Adult, MalignantStudies of the same condition, open and under way.
- 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
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Timmerman, University of Texas Southwestern Medical Center
- Investigators
- Robert Timmerman, MD, Principal investigator, UTSW
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02645487
- Sponsor's protocol ID
- STU 022015-106
- Acronym
- SRS
- Status last verified
- Sep 2026
- First submitted
- 30 Dec 2015
- Last updated
- 7 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-Escalation Study of Stereotactic Radiosurgery for Brain Metastasis Without Whole Brain Radiation
- ClinicalTrials.gov ID
- NCT02645487
- Acronym / sponsor ID
- SRS / STU 022015-106
- Conditions
- Brain Neoplasms, Adult, Malignant
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 18 Dec 2015 (actual)
- Primary completion
- 23 Mar 2025 (actual)
- Study completion
- 23 Dec 2026 (estimated)
- First posted
- 1 Jan 2016 (estimated)
- Results
- Posted 7 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Detailed description
Recently, several large randomized studies have shown that in patients with limited brain metastases, whole brain radiation can be safely deferred when treated with SRS and close surveillance. In light of this, most of such patients are now treated with SRS alone without WBRT. However, the SRS doses set by Radiation Therapy Oncology Group (RTOG) 90-05 continue to be applied to patients without previous cranial irradiation.
The potential insufficiency of current SRS dose for long-term tumor control is of pressing concern. The advances chemotherapy has led to an improvement in overall survival in many patients with metastatic cancer, including malignancies often associated with brain metastases, such as lung (40-50%) and breast (15%). As these patients survive longer, more patients may develop brain metastases and the current dose of SRS may not be adequate to control the brain metastases for the duration of their survival. In fact, there is evidence that the control rate declines with time after SRS, and after 3 years, the local control rate may be only about 60%. In the case of brain metastases from relatively radio-resistant melanoma, the reported 12-months local control rates for SRS range from 52% to 75%. More potent SRS doses could lead to improved long-term control of brain metastases.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | Radiation: Stereotactic RadiosurgeryRadiation, Stereotactic Radiosurgery Dose-Escalation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
- Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
- All brain metastases must be outside the brain stem (midbrain, pons and medulla).
- Patient must have 10 or less brain metastases.
- The maximum diameter of any lesion must be less than or equal to 3.0 cm.
Key exclusion criteria (7 listed)
- Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
- Patients with leptomeningeal metastasis.
- NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
- Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
- Patients with life expectancy < 3 months.
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 RadiosurgeryAlso: SRSRadiation, Stereotactic Radiosurgery Size <= 1cm: 24 Gray (Gy); + 3 Gy incremental escalation up to 30 Gy >1-2cm: 21 Gy; + 3 Gy incremental escalation up to 27 Gy >2-3cm: 18 Gy; + 3 Gy incremental escalation up to 24 Gy | Radiation | Stereotactic Radiosurgery |
Primary outcome
Maximal Tolerated Doses
Time frame: 90 days
The maximal tolerated doses for single-fraction stereotactic radiosurgery, within 90 days from the date of procedure, in patients with brain metastases who have not undergone prior brain irradiation was determined according to the following conditions: if zero or one out of the first seven, two or fewer out of the first nine, three or fewer out of the first twelve, or four or fewer out of the first fifteen of patients within 3-month follow-up experience a dose-limiting toxicity (DLT) as defined in the study protocol, then the dose was escalated to the next dose level according to principal investigator discretion. If three or more of the first nine patients, four or more of the first twelve, or five or more of the first fifteen patients experienced a DLT, then the maximum tolerated dose (MTD) was considered to have been exceeded. Each cohort had 3 maximum dose levels that could be met by reaching the dose escalation conditions.
4 secondary outcomes
Overall Survival
Time frame: 3 years
Time to Progression
Time frame: 3 years
Local Progression Rate
Time frame: 3 years
Response Rate
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Robert Timmerman, MD principal investigator
UTSW
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery in people with Brain Neoplasms, Adult, Malignant, run by University of Texas Southwestern Medical Center 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 15 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 7 Oct 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?
Yes. Results are posted in the registry (first posted 7 Oct 2026). 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?
Maximal Tolerated Doses (time frame: 90 days). 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 7 Oct 2026.