Cerebral Metastases PatientsNCT01861405
Neurococognitive and Functioal Assessment of Patients With Brain Metastases
An observational study of Cerebral Metastases Patients, run by Thomas Jefferson University at 1 site in United States.
Trial summary
The investigators seek to perform an observational study in patients with brain metastases that are to undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) treatment in order to quantify any baseline neurocognitive changes which may result from intracranial disease burden, from radiation… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebral Metastases Patients
- What is being tested?
- neuropsychological testing and quality of life assessments and Functional magnetic resonance imaging
- Type of treatment
- Medical device, Surgery or procedure, Lifestyle or therapy programme
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Mar 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with brain metastases will be referred through the department of Neurosurgery and Radiation-oncology at Thomas Jefferson University Hospital. Healthy subjects will recruited through postings distributed around the hospital and university bulletin boards and through an advertisement in a local newspaper.
Who may be able to join
- Patients with a cumulative intracranial disease burden of up to but not exceeding 8cc.
- Patients with newly diagnosed brain metastases are undergoing WBRT or SRS as previously determined by their oncologist and or radiation oncologist.
- Right or left hand dominance.
- Karnofsky performance status (KPS) equal to or greater than 70.
- 70 years old or younger.
- All non-hematopoietic histologies except melanoma and renal cell carcinoma.
Show all 9Show fewer
- Brainstem lesions are acceptable.
- Normal renal function to tolerate a contrast enhanced MRI scan.
- Patients must provide study specific informed consent prior to study entry.
Who cannot join
- Age less than 18 years old.
- KPS <70.
- Pregnant female.
- Active systemic disease.
- Age greater than 70 years old.
- Patients with leptomeningeal metastases.
Show all 11Show fewer
- Contraindication for MRI such as implanted metal devices, foreign bodies or severe claustrophobia or axial back pain precluding a prolonged MRI study.
- Prior radiation therapy to the brain.
- Poor renal function rendering contrast enhanced MRI un-obtainable.
- Histological diagnosis of small cell lung cancer.
- Craniotomy or other major surgery within 2 weeks of start of either SRS or WBRT.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Yaron Moshel, MD, PhD
About this study
Official title: Neurocognitive and fMRI Activation Changes Observed at Baseline and After Whole Brain Radiation vs. Radiosurgery for Patients With Cerebral Metastases: a Prospective Case-control Analysis.
The investigators seek to perform an observational study in patients with brain metastases that are to undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) treatment in order to quantify any baseline neurocognitive changes which may result from intracranial disease burden, from radiation treatment (WBRT or SRS), or both. To do so, the investigators will compare matched control subjects to patients at time points obtained before and after radiation treatment with either SRS or WBRT. Pre-treatment evaluation will include neurocognitive testing and an assessment of fMRI task-related activation patterns and resting state brain activity. Four and twelve month post-treatment neuropsychological evaluations will be performed and pre- and 4-month post-treatment fMRI scans will be obtained in order to evaluate changes in neurocognitive functioning with a focus on short-term memory and executive function domains. A brief quality of life assessment will also be completed at each study time point. In order to plan treatment strategies in the future it is important to accurately document the effects of intracranial disease burden as well as radiation treatment on neurocognitive functioning, validate fMRI activation tasks for short term memory and executive functioning, and quantify the activation volumes that would potentially be spared in future "cognitive sparing" protocols.
The investigators hypothesize first that the amount and location of intracranial disease burden will represent pre-treatment variables that affect NCF. The compromised NCF will be visualized in both the resting state and task-oriented neurocognitive exercise. The investigators anticipate that any perturbation in resting state caused by intracranial disease burden should be reflected in patients when compared to matched controls.
The investigators hypothesize additionally that cancer patients with brain metastases undergoing radiation treatments will have improved intracranial disease control at the expense of executive and memory function with differences between patients that undergo stereotactic radiosurgery or whole brain radiation alone.
Read the detailed description
This research protocol is designed to perform neuropsychological testing and fMRI scanning in patients with brain metastases that are to undergo either WBRT or SRS treatment at Thomas Jefferson University Hospital. Eligible patients will be referred through the department of Neurosurgery and Radiation-oncology. The patients will complete the informed consent for both the pre- and post-treatment (4 month after WBRT or SRS is completed) fMRI scanning and pre- and post-treatment (4 and 12 months after WBRT or SRS is completed) neuropsychological testing sessions and be told that participation in either the fMRI scans and the neuropsychological testing is voluntary. Patients will also be told that the data will be collected for observational research purposes only and will not directly affect their clinical care. Patients and their insurers will not be additionally billed as a consequence of this study aside from the clinical billing that is consistent with current clinical practice.
The fMRI study will be added on to the pre-existing treatment planning and follow up MRI scan that would be obtained out of clinical necessity without the study.
In order to be able to identify and distinguish normal versus abnormal brain activity patterns associated with the various fMRI tasks and resting state imaging procedures that are part of this study, it will be necessary to scan a subset of healthy (age, education, gender matched) normal controls on the various cognitive and behavioral tasks. This is the only way to determine the validity of the tasks used in terms of their activation properties and the normal brain areas involved in the task. Specifically, the healthy age matched controls are critical for this study as there is no other way to validate the fMRI findings with the hippocampal and executive function activations tasks. Normal matched controls are needed for proper analysis of both the neurocognitive and the neuroimaging data. For the neurocognitive data, the normal control data are needed to construct the Reliable Change Index (RCI) referenced below in the Statistics Section. Also, a comparison to normal is important for estimating the magnitude of any change observed in the patients, to determine if it has clinical relevance. For the neuroimaging data, the normal controls are needed to provide a reference or comparison point to quantify the degree to which the brain-imaging map (referred to as a Statistical Parametric Map, SPM) at each point in time (baseline, post-treatment) deviates from normal. By comparing the patient groups to normals, fMRI activation related to ancillary or idiosyncratic factors during the scan cancel out, leaving only the activation directly related to the cognitive task. Also, determining the presence of new, atypical brain activation sites, lost activation sites, or deactivations, can only be achieved by have a normal SPM brain map for comparison. This applies equally for the task-driven fMRI and the resting state functional connectivity data.
To analyze within-subject analyses with the neuroimaging data, we will examine the neuroimaging data on a within-subject but that will not be the primary quantitative approach to the imaging data, as such within-subject comparisons can be prone to methodologic problems. There is a phenomenon known in the neuroimaging literature as "double dipping" which concerns the ability to distinguish real versus random variation over time. Double dipping refers to the use of test findings at one point in time to constrain or bias the data outcomes and changes registered at a second point in time. More concretely, differences seen in the imaging data may reflect changes in the error, artifactual activations, not change in true-task related activation. To avoid this problem we operationalize change by comparing each patient's imaging data with an index of their deviation from healthy normals at each point in time (pre-surgery/baseline, and post-surgery). This procedure provides a systematic means of quantifying and then comparing the typicality of both pre and postsurgical neurocognitive activations and network organization, a procedure that alleviates concern about "double dipping". This "double dipping" phenomenon and the remedy we propose applies equally for the task-driven fMRI, the resting state functional connectivity data, and the DTI data.
In essence, the methodology proposed minimizes reliance on random, session-specific fluctuations as part of the reference or comparison point for determining change. Our method quantifies the deviation of our patients from normal, examining the relative difference in those deviations as our index of change. In so doing, we avoid the use of our pre-treatment neuroimaging results as the template for comparing and determining change, minimizing concerns of double dipping.
There is no risk associated with the scanning procedure so long as there is no metal in the body. The study of normal volunteers also allows for determination of the stability of the activation findings over time; this allows for verification of the reliability of the fMRI tasks and other procedures over time. Without an understanding of the potential normal change that can occur in brain activation and structure over time, it is impossible to determine if a pathologic change has occurred. This group of normal subjects will be studied in advance in order to validate the fMRI tasks. Furthermore, normal control subjects will be yoked or linked to matched patients and return for additional scanning sessions at the same time points as their matched patient.
- Conditions
- Cerebral Metastases Patients
- Being tested
- neuropsychological testing and quality of life assessments, Standard of Care WBRT or SRS, Functional magnetic resonance imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neuropsychological testing and quality of life assessmentsBehavioural
Standard of Care WBRT or SRSRadiation
Functional magnetic resonance imagingDevice
| Study group | Role | What they receive |
|---|---|---|
| Cerebral metastases subjects | Prior to each subject's radiation treatment (either whole brain radiation therapy or stereotactic radiosurgery), he/she will have fMRI scanning and neuropsychological testing and conduct a quality of life assessment. Each subject will then have standard of care WBRT or SRS treatment. Following WBRT or SRS treatment, subjects will have 4 month follow up fMRI scanning, and have neuropsychological testing and a quality of life assessment 4 months and 12 months post treatment. Receives: Behavioral: neuropsychological testing and quality of life assessments; Radiation: Standard of Care WBRT or SRS; Device: Functional magnetic resonance imaging | |
| Healthy participants | Healthy control subjects will be matched by age, gender, education, ect. to cerebral metastases subjects. Each will have fMRI scannings (3 total), neuropsychological testings (3 total), and quality of life assessments (3 total) at the same time points as their matched cerebral metastases subject. Receives: Behavioral: neuropsychological testing and quality of life assessments; Device: Functional magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish, through neurocognitive testing and fMRI, a correlation between baseline resting state functional brain connectivity, fMRI task related activation patterns and neurocognitive functioning (NCF) in patients with brain metastases.
Measured: Continuous throughout 24 month study participation
Secondary outcomes (3)
To establish from normal control data a reliable change index (RCI) in order to establish the significance and magnitude of any baseline deviations in neurocognitive functioning (NCF) in patients with brain metastases.
Measured: Continuous throughout 24 month study participation
To establish through paired comparisons any significant changes from baseline in NCF and fMRI data after radiation treatmentin patients with brain metastases, adjusted respectively from a reliable change index and statistical parameters.
Measured: Continuous throughout 24 month study participation.
To utilize the data from Aims 1-3 to design a prospective randomized comparison of patient outcomes after SRS alone vs. WBRT, stratified by good and poor baseline NCF groups.
Measured: Continuous throughout 24 month study participation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2013 (estimated)
- Study startMar 2013
- Primary completionMar 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Cerebral Metastases PatientsStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yaron Moshel, MD, PhD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01861405
- Sponsor's protocol ID
- 13D.02
- Status last verified
- Dec 2014
- First submitted
- 20 May 2013
- Last updated
- 18 Dec 2014
- Results posted
- No
Publications
Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.
PubMed 15158627Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990 Feb 22;322(8):494-500. doi: 10.1056/NEJM199002223220802.
PubMed 2405271Herman MA, Tremont-Lukats I, Meyers CA, Trask DD, Froseth C, Renschler MF, Mehta MP. Neurocognitive and functional assessment of patients with brain metastases: a pilot study. Am J Clin Oncol. 2003 Jun;26(3):273-9. doi: 10.1097/01.COC.0000020585.85901.7C.
PubMed 12796600Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004 Jan 1;22(1):157-65. doi: 10.1200/JCO.2004.05.128.
PubMed 14701778Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.
PubMed 16757720Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
PubMed 19801201Brem S, Panattil JG. An era of rapid advancement: diagnosis and treatment of metastatic brain cancer. Neurosurgery. 2005 Nov;57(5 Suppl):S5-9; discusssion S1-4. doi: 10.1093/neurosurgery/57.suppl_5.s4-5.
PubMed 16237289Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005 Oct;75(1):5-14. doi: 10.1007/s11060-004-8093-6.
PubMed 16215811Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998 Nov 4;280(17):1485-9. doi: 10.1001/jama.280.17.1485.
PubMed 9809728Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995 Feb 15;31(4):983-98. doi: 10.1016/0360-3016(94)00550-8.
PubMed 7860415DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.
PubMed 2725874Chang EL, Wefel JS, Maor MH, Hassenbusch SJ 3rd, Mahajan A, Lang FF, Woo SY, Mathews LA, Allen PK, Shiu AS, Meyers CA. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery. 2007 Feb;60(2):277-83; discussion 283-4. doi: 10.1227/01.NEU.0000249272.64439.B1.
PubMed 17290178Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1311-8. doi: 10.1016/j.ijrobp.2008.03.009. Epub 2008 Apr 28.
PubMed 18448270Li J, Bentzen SM, Li J, Renschler M, Mehta MP. Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):64-70. doi: 10.1016/j.ijrobp.2007.09.059.
PubMed 18406884Masterton RA, Carney PW, Jackson GD. Cortical and thalamic resting-state functional connectivity is altered in childhood absence epilepsy. Epilepsy Res. 2012 May;99(3):327-34. doi: 10.1016/j.eplepsyres.2011.12.014. Epub 2012 Jan 24.
PubMed 22281064
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurocognitive and fMRI Activation Changes Observed at Baseline and After Whole Brain Radiation vs. Radiosurgery for Patients With Cerebral Metastases: a Prospective Case-control Analysis.
- ClinicalTrials.gov ID
- NCT01861405
- Acronym / sponsor ID
- 13D.02
- Conditions
- Cerebral Metastases Patients
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Mar 2015 (estimated)
- First posted
- 23 May 2013 (estimated)
- 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 investigators seek to perform an observational study in patients with brain metastases that are to undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) treatment in order to quantify any baseline neurocognitive changes which may result from intracranial disease burden, from radiation treatment (WBRT or SRS), or both. To do so, the investigators will compare matched control subjects to patients at time points obtained before and after radiation treatment with either SRS or WBRT. Pre-treatment evaluation will include neurocognitive testing and an assessment of fMRI task-related activation patterns and resting state brain activity. Four and twelve month post-treatment neuropsychological evaluations will be performed and pre- and 4-month post-treatment fMRI scans will be obtained in order to evaluate changes in neurocognitive functioning with a focus on short-term memory and executive function domains. A brief quality of life assessment will also be completed at each study time point. In order to plan treatment strategies in the future it is important to accurately document the effects of intracranial disease burden as well as radiation treatment on neurocognitive functioning, validate fMRI activation tasks for short term memory and executive functioning, and quantify the activation volumes that would potentially be spared in future "cognitive sparing" protocols.
The investigators hypothesize first that the amount and location of intracranial disease burden will represent pre-treatment variables that affect NCF. The compromised NCF will be visualized in both the resting state and task-oriented neurocognitive exercise. The investigators anticipate that any perturbation in resting state caused by intracranial disease burden should be reflected in patients when compared to matched controls.
The investigators hypothesize additionally that cancer patients with brain metastases undergoing radiation treatments will have improved intracranial disease control at the expense of executive and memory function with differences between patients that undergo stereotactic radiosurgery or whole brain radiation alone.
Detailed description
This research protocol is designed to perform neuropsychological testing and fMRI scanning in patients with brain metastases that are to undergo either WBRT or SRS treatment at Thomas Jefferson University Hospital. Eligible patients will be referred through the department of Neurosurgery and Radiation-oncology. The patients will complete the informed consent for both the pre- and post-treatment (4 month after WBRT or SRS is completed) fMRI scanning and pre- and post-treatment (4 and 12 months after WBRT or SRS is completed) neuropsychological testing sessions and be told that participation in either the fMRI scans and the neuropsychological testing is voluntary. Patients will also be told that the data will be collected for observational research purposes only and will not directly affect their clinical care. Patients and their insurers will not be additionally billed as a consequence of this study aside from the clinical billing that is consistent with current clinical practice.
The fMRI study will be added on to the pre-existing treatment planning and follow up MRI scan that would be obtained out of clinical necessity without the study.
In order to be able to identify and distinguish normal versus abnormal brain activity patterns associated with the various fMRI tasks and resting state imaging procedures that are part of this study, it will be necessary to scan a subset of healthy (age, education, gender matched) normal controls on the various cognitive and behavioral tasks. This is the only way to determine the validity of the tasks used in terms of their activation properties and the normal brain areas involved in the task. Specifically, the healthy age matched controls are critical for this study as there is no other way to validate the fMRI findings with the hippocampal and executive function activations tasks. Normal matched controls are needed for proper analysis of both the neurocognitive and the neuroimaging data. For the neurocognitive data, the normal control data are needed to construct the Reliable Change Index (RCI) referenced below in the Statistics Section. Also, a comparison to normal is important for estimating the magnitude of any change observed in the patients, to determine if it has clinical relevance. For the neuroimaging data, the normal controls are needed to provide a reference or comparison point to quantify the degree to which the brain-imaging map (referred to as a Statistical Parametric Map, SPM) at each point in time (baseline, post-treatment) deviates from normal. By comparing the patient groups to normals, fMRI activation related to ancillary or idiosyncratic factors during the scan cancel out, leaving only the activation directly related to the cognitive task. Also, determining the presence of new, atypical brain activation sites, lost activation sites, or deactivations, can only be achieved by have a normal SPM brain map for comparison. This applies equally for the task-driven fMRI and the resting state functional connectivity data.
To analyze within-subject analyses with the neuroimaging data, we will examine the neuroimaging data on a within-subject but that will not be the primary quantitative approach to the imaging data, as such within-subject comparisons can be prone to methodologic problems. There is a phenomenon known in the neuroimaging literature as "double dipping" which concerns the ability to distinguish real versus random variation over time. Double dipping refers to the use of test findings at one point in time to constrain or bias the data outcomes and changes registered at a second point in time. More concretely, differences seen in the imaging data may reflect changes in the error, artifactual activations, not change in true-task related activation. To avoid this problem we operationalize change by comparing each patient's imaging data with an index of their deviation from healthy normals at each point in time (pre-surgery/baseline, and post-surgery). This procedure provides a systematic means of quantifying and then comparing the typicality of both pre and postsurgical neurocognitive activations and network organization, a procedure that alleviates concern about "double dipping". This "double dipping" phenomenon and the remedy we propose applies equally for the task-driven fMRI, the resting state functional connectivity data, and the DTI data.
In essence, the methodology proposed minimizes reliance on random, session-specific fluctuations as part of the reference or comparison point for determining change. Our method quantifies the deviation of our patients from normal, examining the relative difference in those deviations as our index of change. In so doing, we avoid the use of our pre-treatment neuroimaging results as the template for comparing and determining change, minimizing concerns of double dipping.
There is no risk associated with the scanning procedure so long as there is no metal in the body. The study of normal volunteers also allows for determination of the stability of the activation findings over time; this allows for verification of the reliability of the fMRI tasks and other procedures over time. Without an understanding of the potential normal change that can occur in brain activation and structure over time, it is impossible to determine if a pathologic change has occurred. This group of normal subjects will be studied in advance in order to validate the fMRI tasks. Furthermore, normal control subjects will be yoked or linked to matched patients and return for additional scanning sessions at the same time points as their matched patient.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cerebral metastases subjects | – | Behavioral: neuropsychological testing and quality of life assessments, Radiation: Standard of Care WBRT or SRS, Device: Functional magnetic resonance imagingPrior to each subject's radiation treatment (either whole brain radiation therapy or stereotactic radiosurgery), he/she will have fMRI scanning and neuropsychological testing and conduct a quality of life assessment. Each subject will then have standard of care WBRT or SRS treatment. Following WBRT or SRS treatment, subjects will have 4 month follow up fMRI scanning, and have neuropsychological testing and a quality of life assessment 4 months and 12 months post treatment. |
| Healthy participants | – | Behavioral: neuropsychological testing and quality of life assessments, Device: Functional magnetic resonance imagingHealthy control subjects will be matched by age, gender, education, ect. to cerebral metastases subjects. Each will have fMRI scannings (3 total), neuropsychological testings (3 total), and quality of life assessments (3 total) at the same time points as their matched cerebral metastases subject. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with brain metastases will be referred through the department of Neurosurgery and Radiation-oncology at Thomas Jefferson University Hospital. Healthy subjects will recruited through postings distributed around the hospital and university bulletin boards and through an advertisement in a local newspaper.
Key inclusion criteria (9 listed)
- Patients with a cumulative intracranial disease burden of up to but not exceeding 8cc.
- Patients with newly diagnosed brain metastases are undergoing WBRT or SRS as previously determined by their oncologist and or radiation oncologist.
- Right or left hand dominance.
- Karnofsky performance status (KPS) equal to or greater than 70.
- 70 years old or younger.
Key exclusion criteria (11 listed)
- Age less than 18 years old.
- KPS <70.
- Pregnant female.
- Active systemic disease.
- Age greater than 70 years old.
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 |
|---|---|---|
| neuropsychological testing and quality of life assessments | Behavioural | Cerebral metastases subjects, Healthy participants |
| Standard of Care WBRT or SRS | Radiation | Cerebral metastases subjects |
| Functional magnetic resonance imaging | Device | Cerebral metastases subjects, Healthy participants |
Primary outcome
To establish, through neurocognitive testing and fMRI, a correlation between baseline resting state functional brain connectivity, fMRI task related activation patterns and neurocognitive functioning (NCF) in patients with brain metastases.
Time frame: Continuous throughout 24 month study participation
3 secondary outcomes
To establish from normal control data a reliable change index (RCI) in order to establish the significance and magnitude of any baseline deviations in neurocognitive functioning (NCF) in patients with brain metastases.
Time frame: Continuous throughout 24 month study participation
To establish through paired comparisons any significant changes from baseline in NCF and fMRI data after radiation treatmentin patients with brain metastases, adjusted respectively from a reliable change index and statistical parameters.
Time frame: Continuous throughout 24 month study participation.
To utilize the data from Aims 1-3 to design a prospective randomized comparison of patient outcomes after SRS alone vs. WBRT, stratified by good and poor baseline NCF groups.
Time frame: Continuous throughout 24 month study participation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2014.
- Background: PubMed 15158627Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.
- Background: PubMed 2405271Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990 Feb 22;322(8):494-500. doi: 10.1056/NEJM199002223220802.
- Background: PubMed 12796600Herman MA, Tremont-Lukats I, Meyers CA, Trask DD, Froseth C, Renschler MF, Mehta MP. Neurocognitive and functional assessment of patients with brain metastases: a pilot study. Am J Clin Oncol. 2003 Jun;26(3):273-9. doi: 10.1097/01.COC.0000020585.85901.7C.
- Background: PubMed 14701778Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004 Jan 1;22(1):157-65. doi: 10.1200/JCO.2004.05.128.
- Background: PubMed 16757720Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.
- Background: PubMed 19801201Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
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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.
Yaron Moshel, MD, PhD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cerebral Metastases Patients, run by Thomas Jefferson University 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 9 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 18 Dec 2014. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Meghan Wakefield, RN (215-503-9110, meghan.wakefield@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To establish, through neurocognitive testing and fMRI, a correlation between baseline resting state functional brain connectivity, fMRI task related activation patterns and neurocognitive functioning (NCF) in patients with brain metastases. (time frame: Continuous throughout 24 month study participation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01861405, which also lists 22 linked publications.
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 Dec 2014.