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Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases

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ClinicalTrials.gov Identifier: NCT03223922
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.

Condition or disease Intervention/treatment Phase
Brain Metastases Radiation: whole brain radiation therapy Not Applicable

Detailed Description:

Efforts at treating radiation-induced cognitive and neuropsychiatric declines with medications have shown only minimal preliminary cognitive benefit and do not affect quality of life (QOL). Given the structural and functional brain alterations associated with WBRT, preventing rather than treating these radiation-induced changes may produce more favorable outcomes. Innovative radiotherapy techniques can limit the dose of radiation applied to specific brain structures without compromising tumor coverage. In this light, Radiation Therapy Oncology Group (RTOG) recently published a study evaluating the hippocampal avoidance whole brain radiation therapy (WBRT) in patients with brain metastases. They suggest potential preservation of cognitive function with this approach with no perceived detriment in survival. This concept is currently undergoing investigation in a definitive randomized controlled study (NRG-CC003) in patients receiving prophylactic cranial irradiation for small cell lung cancer. However, no other studies to date have prospectively evaluated avoidance of other particularly sensitive brain regions.

One brain region that has received little attention in the radiotherapy literature is the corpus callosum. The genu of the corpus callosum contains thin, densely packed neural fibers that primarily connect the prefrontal association areas and the anterior inferior parietal regions of the brain. Damage or thinning of the genu is associated with reduced functioning on tests of executive functioning, attention, working memory, processing speed, verbal fluency and memory in a variety of healthy and patient groups including aging, cerebral small vessel disease, traumatic brain injury, multiple sclerosis , human immunodeficiency virus, mild cognitive impairment secondary to Parkinson's disease, and euthymic bipolar disorder. The limited existing data in adults receiving WBRT for brain metastases suggest that they also perceive progressive declines in motivation following treatment. Given its apparent involvement in a wide range of cognitive processes, the genu of the corpus callosum is an excellent candidate for sparing in WBRT. This relatively small area has the potential to preserve cognitive functioning across several domains if guarded from the damaging effects of radiation. In this study patients will receive the standard whole brain radiation dose of 3000 centigray (cGy) in 10 fractions, but intensity modulated radiation therapy will be utilized to limit radiation dose to the genu of the corpus callosum. Patients will undergo cognitive testing at baseline and at 4-, 6- and 12-months following completion of brain radiation to evaluate the study hypothesis.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Patients will be treated to a total dose of 30 Gy with a once daily fractionation schedule of 3 Gy per fraction, administered five days per week.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preservation of Cognition and Neuropsychiatric Functioning With Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases: A Pilot Study
Actual Study Start Date : July 19, 2017
Estimated Primary Completion Date : July 21, 2022
Estimated Study Completion Date : July 21, 2024

Arm Intervention/treatment
Experimental: Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy
Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction
Radiation: whole brain radiation therapy
Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction
Other Name: WBRT




Primary Outcome Measures :
  1. Rate of change of cognitive function [ Time Frame: 4 months ]
    Evaluate changes in cognition from baseline to 4 months following genu-sparing whole brain radiation therapy (GS-WBRT)


Secondary Outcome Measures :
  1. Rate of change of white matter microstructure [ Time Frame: 4, 6 and 12 months ]
    Evaluate change in white matter microstructure following GS-WBRT utilizing diffusion tensor imaging

  2. Rate of change of cognition [ Time Frame: 4, 6 and 12 months ]
    Evaluate changes in cognition from baseline to 4, 6 and 12 months following GS-WBRT

  3. Time to brain metastasis [ Time Frame: 4, 6 and 12 months ]
    Document development of brain metastases in the spared genu of the corpus callosum

  4. Rate of change in QoL [ Time Frame: 4, 6 and 12 months ]
    Document changes in QOL, neuropsychiatric symptoms, and functioning in patients receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT

  5. Rate of change in other frontally-mediated functions [ Time Frame: 4, 6 and 12 months ]
    Document the stability of other frontally-mediated cognitive functions in those receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic proof or unequivocal cytologic proof solid tumor malignancy. This may be obtained from either the primary or any metastatic site
  • Mini Mental State Examination (MMSE) ≥24
  • Age≥ 18 years
  • Karnofsky Performance Status (KPS) ≥70
  • Patient does not have metastases to the genu
  • Patient must be scheduled to undergo treatment with whole brain radiation therapy (WBRT) to manage the brain metastases
  • Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child
  • Patient must have the ability to understand and the willingness to sign a written informed consent document
  • All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines
  • Patient must have a minimal life expectancy of at least 6 months
  • Patients receiving prior stereostatic radiosurgery (SRS) for brain metastases are eligible

Exclusion Criteria:

  • Prior WBRT
  • MMSE<24
  • Patient has brain metastases in the genu
  • Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician prevent informed consent or completion of protocol treatment, and/or follow-up visits.
  • KPS<70
  • Non-native English speakers will be excluded since patients often lose their faculty with the language they acquired second before their native language is affected in the context of cognitive decline. This could adversely affect performance on verbal cognitive tasks.
  • Patients with absolute contraindication to MRI imaging are not eligible for the study

Information from the National Library of Medicine

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): NCT03223922


Contacts
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Contact: Kristin Redmond, MD 410-614-1642 kjanson3@jhmi.edu

Locations
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United States, District of Columbia
Sibley Memorial Hospital Not yet recruiting
Washington, District of Columbia, United States, 20016
Contact: Victoria Croog, MD    202-537-4787    vcroog@jhmi.edu   
United States, Maryland
The SKCCC at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Kristin Redmond, MD    410-614-1642    kjanson3@jhmi.edu   
Sub-Investigator: Tracy Vannorsdall, PhD         
Sub-Investigator: Haris Sair, MD         
Sub-Investigator: Russell Hales, MD         
Sub-Investigator: Lawrence Kleinberg, MD         
Sub-Investigator: Brandi Page, MD         
Sub-Investigator: Deborah Frassica, MD         
Sub-Investigator: Fariba Asrari, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
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Principal Investigator: Kristin Janson The SKCCC at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03223922     History of Changes
Other Study ID Numbers: J1737
IRB00128471 ( Other Identifier: JHM IRB )
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
whole brain radiation therapy
genu of corpus callosum
cognitive function

Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases