Brain MetastasesPhase 1/2NCT03508752
Neurocognitive Decline in Patients With Brain Metastases
A Phase 1/2 study testing Stereotactic Radiosurgery in people with Brain Metastases, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline. 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
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2017to 13 Nov 2027
- Phase
- Phase 1/2
- 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
- Age ≥ 18 years.
- ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
- Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
- Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
- Largest tumor <= 4 cm.
- No prior SRS to the lesions which will be treated on protocol.
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- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. 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
- Prior whole brain radiotherapy
- 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 life expectancy < 4 months.
- Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing 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: Phase I/II Trial to Determine the Neurocognitive Decline in Patients With Multiple (>6) Brain Metastases Treated With Distributed Stereotactic Radiosurgery
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.
Read the detailed description
On review of our experience with treatment for brain metastases since 2009, we have treated over 100 patients with 6 or more metastases in a single radiosurgery session. In the past year and a half (2015-16) there have been approximately 50 patients treated with six or more metastases, indicating that there has been a shift in management of intracranial metastatic disease with increasing preference for radiosurgery despite the presences of greater metastatic burden. The phase I component will accrue 7-15 patients at each dose cohort until the MTD is determined. Once the MTD is reached, the phase II component will commence with a total of 50 patients total enrolled at the MTD, with a study time of 3 years. The primary endpoint of the phase I component is toxicity. The primary endpoint of the phase II component is the change in neurocognitive function, defined by a decline in the Hopkins Verbal Learning Test- Revised delayed recall. Data from the WBRT-alone arm of the PCI-P-120-9801 phase III trial evaluating WBRT plus motexafin gadolinium demonstrated a 30% mean relative decline in the HVLT-R delayed recall score from baseline to 4 months, with a standard deviation of 41% 9,10. More recently, in patients treated with SRS alone for 1-3 metastases versus SRS plus whole brain radiotherapy, the 4-month rates of HVLT-R delayed recall deterioration were 6% and 22% for the SRS alone arm and SRS + whole brain radiotherapy arm, respectively. Given the greater intracranial burden of disease, we estimate the mean relative decline in HVLT-R delayed recall to be intermediate between SRS alone for 1-3 metastases and whole brain radiotherapy. We predict that after SRS for multiple metastases the mean relative decline in delayed recall as 15%, an improvement over the historical control of whole brain radiotherapy alone which had a mean relative decline in HVLT-R delayed recall of 30%.
- Conditions
- Brain Metastases
- 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
Stereotactic Radiosurgery dose is based on the largest tumor size
| Study group | Role | What they receive |
|---|---|---|
| Radiation | Experimental | Stereotactic Radiosurgery Receives: Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: To determine the toxicity within 60 days from the date of SRS, in patients with a greater intracranial disease burden, defined as 6 or more metastases.
Any subject who receives treatment on this protocol will be evaluated for toxicity. Each patient will be assessed for the development of toxicity according to the study calendar. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0.
The following acute (<30 days) and subacute (>30 days - <60 days) toxicities probably or definitely attributable to the protocol treatment, as defined in CTCAE v5.0, will be dose limiting toxicities (DLT) of the study.
Grade 3 or higher neurologic toxicity in the below categories:
- Ataxia
- Symptomatic Central Nervous System Necrosis which is interfering with ADLs (Activities of Daily Living), or requiring treatment with hyperbaric oxygen, Avastin, or resection. Asymptomatic necrosis present on imaging alone does not constitute DLT.
- Cerebral Edema (Grade 4)
- Intracranial Hemorrhage
- Seizure
Any Grade 4 or 5 toxicities definitely attributable to the protocol treatment.
Measured: 60 days
Phase II: Determine the cognitive deterioration (HVLT delayed recall) in patients treated with SRS for multiple metastases (from baseline to 4 months)
The Hopkins Verbal Learning Test (HVLT) is a memory test that gives information about memory.
Each patient will serve as her or his own control, and the relative decline in HVLT-DR (Hopkins Verbal Learning Test- Delayed Recall) score from baseline to 4 month follow-up is defined as
Δ HVLT-DR = (HVLT-R DR at baseline - HVLT-DR at 4 month follow up) / HVLT-DR at baseline.
A positive change indicates a decline in function.
Measured: 4 months
Secondary outcomes (2)
Local control
To determine the optimal dose which will provide local control in patients with a greater intracranial disease burden, defined as 6 or more metastases. Local control is defined as the time between the date of SRS and the first date of documented progressive disease of the treated lesions.
Measured: 90 days
Overall survival (OS)
To determine overall survival (OS). Overall survival is defined as the time between date of SRS (Stereotactic radiosurgery) and date of death.
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 posted26 Apr 2018
- Study start5 Dec 2017
- Primary completion20 Jun 2026
- Study completion13 Nov 2027 (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 Texas Southwestern Medical CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zabi Wardak, University of Texas Southwestern Medical Center
- Investigators
- Zabi Wardak, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03508752
- Sponsor's protocol ID
- STU 122016-064
- Status last verified
- Mar 2026
- First submitted
- 22 Jan 2018
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial to Determine the Neurocognitive Decline in Patients With Multiple (>6) Brain Metastases Treated With Distributed Stereotactic Radiosurgery
- ClinicalTrials.gov ID
- NCT03508752
- Acronym / sponsor ID
- STU 122016-064
- Conditions
- Brain Metastases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 5 Dec 2017 (actual)
- Primary completion
- 20 Jun 2026 (actual)
- Study completion
- 13 Nov 2027 (estimated)
- First posted
- 26 Apr 2018 (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.
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.
Detailed description
On review of our experience with treatment for brain metastases since 2009, we have treated over 100 patients with 6 or more metastases in a single radiosurgery session. In the past year and a half (2015-16) there have been approximately 50 patients treated with six or more metastases, indicating that there has been a shift in management of intracranial metastatic disease with increasing preference for radiosurgery despite the presences of greater metastatic burden. The phase I component will accrue 7-15 patients at each dose cohort until the MTD is determined. Once the MTD is reached, the phase II component will commence with a total of 50 patients total enrolled at the MTD, with a study time of 3 years. The primary endpoint of the phase I component is toxicity. The primary endpoint of the phase II component is the change in neurocognitive function, defined by a decline in the Hopkins Verbal Learning Test- Revised delayed recall. Data from the WBRT-alone arm of the PCI-P-120-9801 phase III trial evaluating WBRT plus motexafin gadolinium demonstrated a 30% mean relative decline in the HVLT-R delayed recall score from baseline to 4 months, with a standard deviation of 41% 9,10. More recently, in patients treated with SRS alone for 1-3 metastases versus SRS plus whole brain radiotherapy, the 4-month rates of HVLT-R delayed recall deterioration were 6% and 22% for the SRS alone arm and SRS + whole brain radiotherapy arm, respectively. Given the greater intracranial burden of disease, we estimate the mean relative decline in HVLT-R delayed recall to be intermediate between SRS alone for 1-3 metastases and whole brain radiotherapy. We predict that after SRS for multiple metastases the mean relative decline in delayed recall as 15%, an improvement over the historical control of whole brain radiotherapy alone which had a mean relative decline in HVLT-R delayed recall of 30%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiation | Experimental | Radiation: Stereotactic RadiosurgeryStereotactic Radiosurgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years.
- ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
- Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
- Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
- Largest tumor <= 4 cm.
Key exclusion criteria (5 listed)
- Prior whole brain radiotherapy
- 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 life expectancy < 4 months.
- Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
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 RadiosurgeryStereotactic Radiosurgery dose is based on the largest tumor size | Radiation | Radiation |
Primary outcome
Phase I: To determine the toxicity within 60 days from the date of SRS, in patients with a greater intracranial disease burden, defined as 6 or more metastases.
Time frame: 60 days
Any subject who receives treatment on this protocol will be evaluated for toxicity. Each patient will be assessed for the development of toxicity according to the study calendar. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. The following acute (<30 days) and subacute (>30 days - <60 days) toxicities probably or definitely attributable to the protocol treatment, as defined in CTCAE v5.0, will be dose limiting toxicities (DLT) of the study. Grade 3 or higher neurologic toxicity in the below categories: * Ataxia * Symptomatic Central Nervous System Necrosis which is interfering with ADLs (Activities of Daily Living), or requiring treatment with hyperbaric oxygen, Avastin, or resection. Asymptomatic necrosis present on imaging alone does not constitute DLT. * Cerebral Edema (Grade 4) * Intracranial Hemorrhage * Seizure Any Grade 4 or 5 toxicities definitely attributable to the protocol treatment.
Phase II: Determine the cognitive deterioration (HVLT delayed recall) in patients treated with SRS for multiple metastases (from baseline to 4 months)
Time frame: 4 months
The Hopkins Verbal Learning Test (HVLT) is a memory test that gives information about memory. Each patient will serve as her or his own control, and the relative decline in HVLT-DR (Hopkins Verbal Learning Test- Delayed Recall) score from baseline to 4 month follow-up is defined as Δ HVLT-DR = (HVLT-R DR at baseline - HVLT-DR at 4 month follow up) / HVLT-DR at baseline. A positive change indicates a decline in function.
2 secondary outcomes
Local control
Time frame: 90 days
Overall survival (OS)
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 18 Sep 2026.
- 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.
Zabi Wardak, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Stereotactic Radiosurgery in people with Brain Metastases, 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 11 inclusion and 5 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 18 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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?
Phase I: To determine the toxicity within 60 days from the date of SRS, in patients with a greater intracranial disease burden, defined as 6 or more metastases. (time frame: 60 days). The study lists 2 primary outcomes in all. 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 18 Sep 2026.