Avoiding the Hippocampus During Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
- Conditions
- Cognitive/Functional EffectsMetastatic CancerUnspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Radiation: intensity-modulated radiation therapy
- Registration Number
- NCT01227954
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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.
Secondary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 113
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description WBRT with Hippocampal Avoidance intensity-modulated radiation therapy Whole brain radiotherapy (WBRT) with hippocampal avoidance using intensity-modulated radiation therapy (IMRT)
- Primary Outcome Measures
Name Time Method Percent Change in Delayed Recall at 4 Months as Measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) 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\*\[(baseline score - 4 month score)/ baseline score\]
- Secondary Outcome Measures
Name Time Method Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) 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.
ApoE4 Genotype and Other Potentially Predictive Biomarkers of Cognitive Function 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
Percent Change at 4 Months in Visual Learning Measured by Cogstate's One Card Learning Test (OCLT) 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\*\[(baseline score - 4 month score)/ baseline score\].
Percent Change at 4 Months in Auditory Learning Measured by Cogstate's International Shopping List Test (ISLT) 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\*\[(baseline score - 4 month score)/ baseline score\].
Progression-free Survival 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).
Quality of Life as Measured by the Barthel Index of Activities of Daily Living (ADL) 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 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.
The Frequency of Patients With Grade 3 and Higher Adverse Events (AE) Related to Treatment 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
Trial Locations
- Locations (63)
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Arizona Center for Cancer Care - Peoria
🇺🇸Peoria, Arizona, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Arizona Oncology - Tucson
🇺🇸Tucson, Arizona, United States
Veterans Affairs Medical Center - Long Beach
🇺🇸Long Beach, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Radiological Associates of Sacramento Medical Group, Incorporated
🇺🇸Sacramento, California, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Florida Cancer Center - Palatka
🇺🇸Palatka, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
Center for Cancer Care at Goshen General Hospital
🇺🇸Goshen, Indiana, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
NSMC Cancer Center - Peabody
🇺🇸Danvers, Massachusetts, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
St. Barnabas Medical Center Cancer Center
🇺🇸Livingston, New Jersey, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
New York Oncology Hematology, PC at Albany Regional Cancer Care
🇺🇸Albany, New York, United States
Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
Adena Regional Medical Center
🇺🇸Chillicothe, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Southwest General Health Center
🇺🇸Middleburg Heights, Ohio, United States
Willamette Valley Cancer Center - Eugene
🇺🇸Eugene, Oregon, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Adams Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Regional Cancer Center - Erie
🇺🇸Erie, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
York Cancer Center at Apple Hill Medical Center
🇺🇸York, Pennsylvania, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Texas Oncology, PA at Harris Center HEB
🇺🇸Bedford, Texas, United States
Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital
🇺🇸Fort Worth, Texas, United States
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
🇺🇸Murray, Utah, United States
Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land
🇺🇸Sugar Land, Texas, United States
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
London Regional Cancer Program at London Health Sciences Centre
🇨🇦London, Ontario, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
Baptist-South Miami Regional Cancer Program
🇺🇸Miami, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Methodist Cancer Center at Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Memorial Hermann Hospital - Memorial City
🇺🇸Houston, Texas, United States
M. D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
CCOP - Virginia Mason Research Center
🇺🇸Seattle, Washington, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Providence Cancer Center at Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States