Brain Neoplasms, Adult, MalignantPhase 2NCT01414738
Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases
A Phase 2 study testing Radiotherapy in people with Brain Neoplasms, Adult, Malignant, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The investigators hypothesize that avoidance of the hippocampal region with WBRT (Whole-Brain Radiotherapy ) may delay or reduce the onset, frequency, and/or severity of NCF (neurocognitive function) decline, as measured with clinical neurocognitive tools. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Brain Neoplasms, Adult, Malignant
- What is being tested?
- Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2011to 16 Dec 2019
- Phase
- Phase 2
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy.. Direct biopsy of CNS (central nervous system) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent. Patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy.
- Patients with measurable brain metastasis outside a 5-mm margin around either hippocampus
- Patients with measurable brain metastasis who have not been or will not be treated with SRS (stereotactic radiosurgery ) or surgical resection (Note: These treatment options are only permitted at relapse)
- History/physical examination within 28 days prior to registration
- Patients must fall into RTOG (Radiation Therapy Oncology Group) recursive partitioning analysis (RPA) class I or II
- Patients must have a life expectancy of at least 4 months.
Show all 11Show fewer
- Age ≥ 18 years
- Karnofsky performance status ≥ 70
- Patients must provide study-specific informed consent prior to study entry
- Women of childbearing potential and male participants must practice adequate contraception
- Women of childbearing potential must have a negative, qualitative serum pregnancy test ≤2 weeks prior to study entry
Who cannot join
- Patients with greater than 9 discrete metastases on MRI.
- Patients with leptomeningeal metastases
- Patients with measurable brain metastasis not resulting from small cell lung cancer and germ cell malignancy
- Plan for chemotherapy or targeted therapies during WBRT or over the subsequent 7 days
- Contraindication to MR (Magnetic resonance) imaging such as implanted metal devices or foreign bodies, severe claustrophobia AND patients unable to receive gadolinium contrast agents
- Serum creatinine > 1.4 mg/dl ≤ 28 days prior to study entry
- Prior radiation therapy to the brain
- Patients planning to undergo radiosurgery to any CNS lesion OR patients planning to have surgical resection of ALL of their CNS lesions
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 II Trial of Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases
The investigators hypothesize that avoidance of the hippocampal region with WBRT (Whole-Brain Radiotherapy ) may delay or reduce the onset, frequency, and/or severity of NCF (neurocognitive function) decline, as measured with clinical neurocognitive tools.
Read the detailed description
We propose to use conformal avoidance of the hippocampal region during whole brain radiotherapy to reduce the dose to the hippocampi, thereby putatively limiting the radiation-induced inflammation of the hippocampal region and subsequent alteration of the microenvironment of the neural progenitor cells
- Conditions
- Brain Neoplasms, Adult, Malignant
- Being tested
- Radiotherapy
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyRadiation
Hippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost
| Study group | Role | What they receive |
|---|---|---|
| Radiation | Experimental | Whole-Brain Radiotherapy Receives: Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score
The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.
*Delayed*recall was measured by recalling the 12 targets after a 20-minute delay.
1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, 3 months
Secondary outcomes (17)
Mean Change in *Immediate* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.
*Immediate* recall was measured by memorizing a list of 12 targets for 3 consecutive trials.
1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, at 3 months
Mean Change in *Delayed Recognition* Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories.
*Delayed recognition* was measured by using recognition discrimination index.
1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, 3 months
Mean Change in Neurocognitive Function as Measured by Controlled Word Association Test
Controlled Word Association Test (COWAT) is used to assess language and executive/frontal skills. The patient produces as many words as possible in 1 min. (each) for a specific letter (C, F, L or P, R, W). Requires about 5 min to complete.
1 point is awarded for each word produced. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, at 3 months
Mean Change in Trail Making Test (TMT- A) Score
Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers.
The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B.
In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order.
Possible score ranges from 0-3 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, at 3 months
Mean Change in Trail Making Test (TMT- B) Score
Trail Making Test (TMT) is a measure of visuospatial scanning, attention, sequencing, and speed and executive function. Patients must "connect the dots" either in a numbered sequence or alternating letters and numbers.
The TMT has two parts that are referred to as the Trail Making Test Part A and the Trail Making Test Part B.
In Part B, the circles include both numbers (1 - 13) and letters (A - L). Possible score ranges from 0-5 minutes with higher score (more seconds/minutes) indicating significant cognitive impairment.
Measured: Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Medical Outcomes Scale (MOS)
Medical Outcomes Scale (MOS) assess cognitive function with possible score range from 0-100, with higher scores indicating better outcome.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Mini-Mental Status Examination (MMSE)
Mini-Mental Status Examination (MMSE) is a brief, standardized tool to grade patients' global cognitive function. Possible scores range from 0-30, with lower score indicating severe cognitive impairment.
Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
Measured: Baseline, at 3 months
Mean Change in Relative Fatigue as Measured by Multidimensional Fatigue Inventory (MFI-20) Scores
The MFI-20 is a multidimensional, self-reporting instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Possible subscore ranges from 4 to 20 is reported for each dimension, with 20 corresponding to maximal fatigue.
Measured: Baseline, 3 months
Cumulative Incidence of Local Failure
Cumulative incidence of local failure, defined as tumor recurrence . Percent local failure at 1 year.
The Cox proportional hazards regression model will be used to evaluate Cumulative incidence of local failure.
This is to evaluate local control of brain metastases treated with integrated boost.
Measured: 1 year
Cumulative Incidence of Intracranial Failure
Cumulative incidence of intracranial failure was estimated by the Cox proportional hazards regression model.
Intracranial failure is any failure in the brain.
Measured: 1 year
Percentage of Participants With Local Failures Within the Region of Brain Within the CTV Receiving 20 Gy
Percentage of participants with local failures within the region of brain within the CTV (Clinical Target Volume ) receiving 20 Gy
Measured: 1 year
Number of Participants With Recurrence in the Hippocampus
Recurrence in the hippocampus was noted after hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT)
Measured: 5 months
Median Progression Free Survival
Tumor progression is measured radiographically. The Kaplan-Meier estimator was used to determine the median time to death for this patient population.
Measured: 39 months
Median Overall Survival.
Overall survival is measured by the Kaplan-Meier estimator used to determine the median overall survival for this patient population.
Measured: 39 months
Number of Adverse Events Grade 3 or Higher Based on CTCAE (Common Terminology Criteria for Adverse Events) Criteria.
The adverse event (AE) including any adverse event would be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: From start of treatment up to 39 months
Health-related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy With Brain Subscale (FACT-BR)
Quality of life will be assessed using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). The FACT-BR is a multidimensional, self-report quality of life instrument specifically designed and validated for use with brain malignancy patients. It is written at the 4th grade reading level and can be completed in 5-10 minutes with little or no assistance in patients who are not neurologically incapacitated. It measures quality of life related to symptoms or problems across 5 scales: physical well-being (7 items); social/family well-being (7 items);emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items).
Items are rated on a 5-point scale (0-5): 0-"not at all", 1- "a little bit", 2-"somewhat", 3-"quite a bit" and 4-"very much", with HIGHER scores indicating a better quality of life.
Measured: 39 months
Health-related Quality of Life as Assessed by Euroqol EQ-5D
The EQ (Euroqol)-5D (5 Dimension) health related quality of life questionnaire is a standardized instrument for use as a measure of health outcome.
Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. . The US version of the EQ-5D will be used, to enable mapping of general HR-QoL (Health-related quality of life) scores from EQ-5D scores into health state utility scores (ranging from 0 to 1) for the US population.
Possible scores range from 0 to 1, with HIGHER scores indicating a better quality of life.
Measured: 39 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2011 (estimated)
- Study start18 Oct 2011
- Primary completion16 Dec 2019
- Study completion16 Dec 2019
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 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, UT Southwestern Medical Center Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01414738
- Sponsor's protocol ID
- STU 042011-050
- Status last verified
- Mar 2020
- First submitted
- 10 Aug 2011
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Hippocampal-Avoiding Whole Brain Irradiation With Simultaneous Integrated Boost for Treatment of Brain Metastases
- ClinicalTrials.gov ID
- NCT01414738
- Acronym / sponsor ID
- STU 042011-050
- Conditions
- Brain Neoplasms, Adult, Malignant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 18 Oct 2011 (actual)
- Primary completion
- 16 Dec 2019 (actual)
- Study completion
- 16 Dec 2019 (actual)
- First posted
- 11 Aug 2011 (estimated)
- Results
- Posted 26 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that avoidance of the hippocampal region with WBRT (Whole-Brain Radiotherapy ) may delay or reduce the onset, frequency, and/or severity of NCF (neurocognitive function) decline, as measured with clinical neurocognitive tools.
Detailed description
We propose to use conformal avoidance of the hippocampal region during whole brain radiotherapy to reduce the dose to the hippocampi, thereby putatively limiting the radiation-induced inflammation of the hippocampal region and subsequent alteration of the microenvironment of the neural progenitor cells
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: RadiotherapyWhole-Brain Radiotherapy |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pathologically (histologically or cytologically) proven diagnosis of a non-hematopoietic malignancy other than small cell lung cancer and germ cell malignancy.. Direct biopsy of CNS (central nervous system) lesions is not necessarily required although could constitute an allowed site of tissue confirmation as medically prudent. Patients who have been disease free for more than 5 years prior to the appearance of CNS metastases should undergo repeat biopsy of either a systemic metastasis or the CNS metastases to confirm the recurrent malignancy.
- Patients with measurable brain metastasis outside a 5-mm margin around either hippocampus
- Patients with measurable brain metastasis who have not been or will not be treated with SRS (stereotactic radiosurgery ) or surgical resection (Note: These treatment options are only permitted at relapse)
- History/physical examination within 28 days prior to registration
- Patients must fall into RTOG (Radiation Therapy Oncology Group) recursive partitioning analysis (RPA) class I or II
Key exclusion criteria (8 listed)
- Patients with greater than 9 discrete metastases on MRI.
- Patients with leptomeningeal metastases
- Patients with measurable brain metastasis not resulting from small cell lung cancer and germ cell malignancy
- Plan for chemotherapy or targeted therapies during WBRT or over the subsequent 7 days
- Contraindication to MR (Magnetic resonance) imaging such as implanted metal devices or foreign bodies, severe claustrophobia AND patients unable to receive gadolinium contrast agents
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 |
|---|---|---|
| RadiotherapyHippocampal-Avoiding Whole Brain Irradiation with Simultaneous Integrated Boost | Radiation | Radiation |
Primary outcome
Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score
Time frame: Baseline, 3 months
The HVLT-R is a validated test to assess neurocognitive function and it incorporates 6 different forms, each including 12 nouns (targets) with 4 words drawn from 3 semantic categories. *Delayed*recall was measured by recalling the 12 targets after a 20-minute delay. 1 point is awarded for each successfully recalled target. There is no range- recalling more is more memory. Mean change was calculated by the following formula: 100*(3 month - baseline) / baseline
17 secondary outcomes
Mean Change in *Immediate* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Time frame: Baseline, at 3 months
Mean Change in *Delayed Recognition* Score by Hopkins Verbal Learning Test-Revised (HVLT-R)
Time frame: Baseline, 3 months
Mean Change in Neurocognitive Function as Measured by Controlled Word Association Test
Time frame: Baseline, at 3 months
Mean Change in Trail Making Test (TMT- A) Score
Time frame: Baseline, at 3 months
Mean Change in Trail Making Test (TMT- B) Score
Time frame: Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Medical Outcomes Scale (MOS)
Time frame: Baseline, at 3 months
Mean Change in Cognitive Function as Measured by Mini-Mental Status Examination (MMSE)
Time frame: Baseline, at 3 months
Mean Change in Relative Fatigue as Measured by Multidimensional Fatigue Inventory (MFI-20) Scores
Time frame: Baseline, 3 months
Cumulative Incidence of Local Failure
Time frame: 1 year
Cumulative Incidence of Intracranial Failure
Time frame: 1 year
Percentage of Participants With Local Failures Within the Region of Brain Within the CTV Receiving 20 Gy
Time frame: 1 year
Number of Participants With Recurrence in the Hippocampus
Time frame: 5 months
Median Progression Free Survival
Time frame: 39 months
Median Overall Survival.
Time frame: 39 months
Number of Adverse Events Grade 3 or Higher Based on CTCAE (Common Terminology Criteria for Adverse Events) Criteria.
Time frame: From start of treatment up to 39 months
Health-related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy With Brain Subscale (FACT-BR)
Time frame: 39 months
Health-related Quality of Life as Assessed by Euroqol EQ-5D
Time frame: 39 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Brain Neoplasms, Adult, Malignant
Active, not recruitingPhase 1
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma
Active, not recruiting
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis
Brain Neoplasms, Adult, Malignant
Active, not recruitingPhase 1
RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)
Recurrent Glioblastoma
Active, not recruitingEarly Phase 1
Fimepinostat in Treating Brain Tumors in Children and Young Adults
Diffuse Intrinsic Pontine Glioma, Recurrent Anaplastic Astrocytoma
Active, not recruitingObservational study
Social Health, Activity Behaviors, and Quality of Life Among Young Adult Cancer Survivors
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8
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
UT Southwestern Medical Center Dallas
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 Radiotherapy 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 11 inclusion and 8 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: finished, as of the sponsor's last update on 26 Jan 2021. 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?
Yes. Results are posted in the registry (first posted 26 Jan 2021). 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?
Mean Change in *Delayed* Recall Score by Hopkins Verbal Learning Test-Revised (HVLT-R DR) Score (time frame: Baseline, 3 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 26 Jan 2021; AzTrials last refreshed its copy on 29 Oct 2026.