Neurocognitive Decline in Patients With Brain Metastases

June 5, 2026 updated by: Zabi Wardak, University of Texas Southwestern Medical Center

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
  3. Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
  4. 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.
  5. Largest tumor <= 4 cm.
  6. No prior SRS to the lesions which will be treated on protocol.

  7. 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).
  8. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

  1. Prior whole brain radiotherapy
  2. 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.)
  3. Patients with life expectancy < 4 months.
  4. Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
  5. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Radiation
Stereotactic Radiosurgery
Radiation: Stereotactic Radiosurgery
Stereotactic Radiosurgery dose is based on the largest tumor size

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
60 days
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.
4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Local control
Time Frame: 90 days
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.
90 days
Overall survival (OS)
Time Frame: 2 years
To determine overall survival (OS). Overall survival is defined as the time between date of SRS (Stereotactic radiosurgery) and date of death.
2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To determine neurocognitive outcomes
Time Frame: 3 years
via HVLT (Hopkins Verbal Learning Test) and quality of life via FACT-Br (Functional Assessment of Cancer Therapy) amongst patients treated with > 6 metastases via SRS. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
To determine the time to distant brain recurrence
Time Frame: 3 years
distant brain recurrence is defined as time between date of SRS and development of new metastases. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
To determine the incidence of salvage WBRT or radiosurgery
Time Frame: 4 months
WBRT is defined as whole brain radiation therapy. This is an exploratory outcome and was added as a secondary outcome in error.
4 months
Prospectively collect and analyze histology and mutational/hormone status. This is an exploratory outcome and was added as a secondary outcome in error.
Time Frame: 3 years
Patients' disease status over time
3 years
Prospectively collect and analyze hippocampal dose and relation to neurocognitive decline
Time Frame: 3 years
Hippocampal dose measured in cGy (centigray); neurocognitive decline assessed by HVLT (Hopkins Verbal Learning Test). This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze whole brain integral dose, V8, V10, and V12 and relation to toxicity
Time Frame: 3 years
assessed by CTCAE v5.0. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze the total treatment time
Time Frame: 3 years
Treatment time measured in hours, minutes, and seconds. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze total brain metastases volume and relation to local control, neurocognitive outcome, quality of life, and toxicity
Time Frame: 3 years
Total brain metastases volume (cc). This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze the size of treated brain metastases
Time Frame: 3 years
Measured in millimeters/centimeters. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze the number of brain metastases and relation to local control, neurocognitive outcome, quality of life, and toxicity
Time Frame: 3 years
How the number of brain metastases affects patients' health over time. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze neurologic symptoms at the time of SRS
Time Frame: 3 years
Symptoms at time of stereotactic radiosurgery. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze the effect of controlled or uncontrolled systemic disease on local control, neurocognitive outcome, quality of life and toxicity
Time Frame: 3 years
How patients are affected by systemic disease over time. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze the effect of the type of prior systemic therapy on local control, neurocognitive outcome, quality of life and toxicity
Time Frame: 3 years
Prior systemic therapy includes cytotoxic, targeted, or immune therapy. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
Prospectively collect and analyze standard patient demographics
Time Frame: 3 years
Patient demographics include age in years, performance status using ECOG (Eastern Cooperative Oncology Group)/Zubrod performance scale, and gender. This is an exploratory outcome and was added as a secondary outcome in error.
3 years
To prospectively collect treatment time of patients treated for multiple metastases
Time Frame: 2 years
reported in a routine manner at scheduled times during the trial. This is an exploratory outcome and was added as a secondary outcome in error.
2 years
To determine the incidence of development of leptomeningeal disease
Time Frame: 2 years
Leptomeningeal disease is an exclusion criteria for the study. This is an exploratory outcome and was added as a secondary outcome in error.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Texas Southwestern Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zabi Wardak, MD, University of Texas Southwestern Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 5, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 20, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 13, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU 122016-064

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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