Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
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|ClinicalTrials.gov Identifier: NCT01227954|
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : September 27, 2017
Last Update Posted : September 27, 2017
RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells.
PURPOSE: This phase II trial is studying how well avoiding the hippocampus during whole-brain radiation therapy works in treating patients with brain metastases.
|Condition or disease||Intervention/treatment||Phase|
|Cognitive/Functional Effects Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific||Radiation: intensity-modulated radiation therapy||Phase 2|
- Evaluate delayed recall as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R) at 4 months after hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) in patients with brain metastasis.
- Evaluate auditory and visual learning and memory, as assessed by two CogState tests (International Shopping List Test and One Card Learning Test), after HA-WBRT in these patients.
- Compare psychometric properties of the 2 CogState tests to the HVLT-R for the assessment of memory decline after HA-WBRT in these patients.
- Evaluate health-related quality of life [as assessed by the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR) and the Barthel Index of Activities of Daily Living (ADLs)] after HA-WBRT in these patients.
- Evaluate time to radiographic progression after HA-WBRT in these patients.
- Evaluate overall survival of these patients after HA-WBR.
- Evaluate the adverse events of HA-WBR.
- Evaluate predictive biomarkers of cognitive function.
OUTLINE: This is a multicenter study.
Patients undergo 10 fractions of intensity-modulated whole-brain radiotherapy (WBRT), avoiding hippocampal (HA) regions, once daily, 5 days a week, for 2-2½ weeks.
Patients neurocognitive functions (delayed recall, auditory and visual learning, and memory) are evaluated by the Hopkins Verbal Learning Test-Revised (HVTL-R), The One Card Learning Test (OCLT), and the International Shopping List Test (ISLT) at baseline and periodically during study.
Patients may undergo serum, plasma, or whole blood collection at baseline and at 4 months after completion of HA-WBRT for correlative studies.
Patients may complete the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR), and the Barthel Index of Activities of Daily Living (ADLs) quality-of-life questionnaires at baseline and periodically during study and follow up.
After completion of study therapy, patients are followed up periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||113 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Hippocampal Avoidance During Whole Brain Radiotherapy for Brain Metastases|
|Study Start Date :||March 2011|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||December 2016|
WBRT with Hippocampal Avoidance
Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
Radiation: intensity-modulated radiation therapy
30 Gy in 10 fractions to the whole brain using intensity-modulated radiation therapy excluding the hippocampal avoidance area. Bilateral hippocampal contours manually generated on the fused planning MRI CT image set by the treating physician according to protocol-specified contouring instructions. Hippocampal avoidance regions generated by three-dimensionally expanding the hippocampal contours by 5 mm.
Other Name: IMRT
- Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: Baseline and 4 months from start of treatment ]Change in Hopkins Verbal Learning Test-Revised delayed recall (HVLT_R DR) score from baseline to 4 months after the start of treatment calculated as (baseline score - 4 month score)/ baseline score. A positive change indicates a decline in function. The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms, helping to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. Delayed recall involves recalling a list of 12 targets after a 20-minute delay. The score is the sum of the number of targets correctly recalled. Percent change calculated as 100*[(baseline score - 4 month score)/ baseline score]
- Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT) [ Time Frame: Baseline and 4 months from start of treatment ]The score is the total number of correct responses made in remembering the list on three consecutive trials in a single session. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in ISLT score from baseline to 4 months was calculated as 100*[(baseline score - 4 month score)/ baseline score].
- Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT) [ Time Frame: Baseline and 4 months from start of treatment ]The score is the arcsine of the square root of the proportion of correct responses. A higher score indicates a better performance. Each patient served as her or his own control, and the percent change in OCLT score from baseline to 4 months was calculated as 100*[(baseline score - 4 month score)/ baseline score].
- Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) [ Time Frame: Baseline and 4 months from start of treatment ]The FACT-Br is a 19-item self-report instrument designed to measure multidimensional quality of life in patients with brain cancer. It is to be administered with the FACT-General. The FACT-G is a validated, 27-item measure where a higher score represents higher QOL. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, 0=Not a lot to 4=Very much. All subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range 0-108 for FACT-G total, 0-28 for physical, social, functional subscales, 0-24 for emotional subscale, 0-76 for brain subscale. Certain items must be reversed before it is added by subtracting the response from 4. Subscale requires >= 50% of items to be completed while the overall response rate must be > 80%. If items are missing, the subscale scores can be prorated.
- Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) [ Time Frame: Baseline and 4 months from start of treatment ]The Barthel Index of Activities of Daily Living (ADL) is a 10-item assessment. Patient scores on the ADL range from 0 to 20 with lower scores indicating declining functional status.
- Overall Survival [ Time Frame: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.) ]Overall survival was measured from registration to the date of death or last known follow-up (censored). Kaplan-Meier estimator was used to median survival time and 95% confidence interval.
- Progression-free Survival [ Time Frame: Analysis occurs after all patients have been on study for at least 4 months. (Patients are followed from registration to death or study termination whichever occurs first.) ]Progression (radiographic) is defined as an increase in perpendicular bidimensional tumor area (at lease 50% for lesions < 1cm, at least 25% for lesions >=1cm) for any of the 1-3 tracked brain metastases, or the appearance of any new brain metastasis on a follow-up MRI. Progression-free survival was calculated instead of time to progression. Progression-free survival time was measured from registration to the date of progression, death, or last known follow-up (censored). The Kaplan-Meier method used to determine median time (along with 95% confidence intervals).
- The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to Treatment [ Time Frame: From start of treatment to 12 months from start of treatment ]For each patient the highest grade adverse event related to treatment was calculated. Those with their highest grade of 3 or higher were counted. Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE
- ApoE4 Genotype and Other Potentially Predictive Biomarkers of Cognitive Function [ Time Frame: Baseline and 4 months from start of treatment ]Per the protocol, the feasibility of the proposed translational studies were to be assessed following completion of accrual and sample collection. The decision was made not to pursue this outcome measure. No assays were performed and no data were collected for this Outcome Measure
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01227954
|Principal Investigator:||Minesh P. Mehta, MD||University of Maryland Medical Systems|