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

Brain Metastases Clinical Trial

Official title:

Preservation of Cognition and Neuropsychiatric Functioning With Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03223922
• Other study ID #: J1737
• Secondary ID: IRB00128471
• Status: Recruiting
• Phase: N/A
• Start date: July 19, 2017
• Est. completion date: December 2030

Study information

• Verified date: June 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Kristin Redmond, MD
• Phone: 410-614-1642
• Email: kjanson3[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2030
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
United States	The SKCCC at Johns Hopkins	Baltimore	Maryland
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change of cognitive function	Evaluate changes in cognition from baseline to 4 months following genu-sparing whole brain radiation therapy (GS-WBRT)	4 months
Secondary	Rate of change of white matter microstructure	Evaluate change in white matter microstructure following GS-WBRT utilizing diffusion tensor imaging	4, 6 and 12 months
Secondary	Rate of change of cognition	Evaluate changes in cognition from baseline to 4, 6 and 12 months following GS-WBRT	4, 6 and 12 months
Secondary	Time to brain metastasis	Document development of brain metastases in the spared genu of the corpus callosum	4, 6 and 12 months
Secondary	Rate of change in QoL	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	4, 6 and 12 months
Secondary	Rate of change in other frontally-mediated functions	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.	4, 6 and 12 months