Cognitive Biomarkers in Pediatric Brain Tumor Patients

Childhood Brain Tumor Clinical Trial

Official title:

Cognitive Biomarkers in Pediatric Brain Tumor Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02914067
• Other study ID #: 201609023
• Status: Recruiting
• Phase: N/A
• Start date: October 26, 2016
• Est. completion date: January 31, 2027

Study information

• Verified date: December 2023
• Source: Washington University School of Medicine
• Contact: Stephanie Perkins, M.D.
• Phone: 314-273-2931
• Email: sperkins[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will focus on three cohorts of brain tumor patients aged, 4-18 years, to answer two critical questions: 1) Can the investigators acquire high quality data relevant to cognitive function during the peri-diagnostic period and, 2) can the investigators develop predictive models for cognitive outcomes using serial examination of functional imaging and cognitive function. Any patient with a newly diagnosed brain tumor aged 4-18 will be eligible for enrollment in cohort 1. Only patients with previously diagnosed tumors of the posterior fossa will be eligible for cohort 2. For cohort 3, eligible patients will include patients with a clinical diagnosis of posterior fossa syndrome with physical impairments that prohibit completion of the NIH Toolbox Cognitive Battery. The investigators have decided to expand the eligible tumor types to better capture the most significant deficit variability that can be caused by tumors outside the posterior fossa. Thus, this focus will provide a platform to analyze the impact that different tumor types and different standard treatments have on cognitive dysfunction. The rationale for inclusion of subjects on cohort 3 is that posterior fossa syndrome is one of the most cognitively devastating diagnoses following a posterior fossa surgery. The causes of posterior fossa syndrome and unknown and there are currently no interventions to improve symptoms. RsfcMRI would offer a novel and non-invasive assessment of posterior fossa syndrome patients by assessing connectivity within and outside of the cerebellum. Expanding the tumor eligibility will allow us to further explore the effect tumor location will have on cognitive testing and rsfcMRI. Here, repeated evaluations on and off therapy will provide the necessary data points to establish trajectories of cognitive development and recovery in this population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2027
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 18 Years

Eligibility

Cohort 1 (30 patients will be enrolled to this cohort)

Inclusion Criteria:

• Between 4 and 18 years of age, inclusive

• Newly diagnosed primary brain tumor of any location and any histology

• Life expectancy of at least one year

• Able to understand and willing to consent or assent to the research proposed, along with consent of legal guardian(s) if applicable

Exclusion Criteria:

• Presence of visual impairment to an extent that the patient is unable to complete the computer testing

• Contraindication to MRI scan (i.e. due to cardiac pacemaker)

• Programmable Shunt

Cohort 2 (150 patients will enrolled to this cohort. This may include some or all of the patients enrolled to Cohort 1.)

Inclusion Criteria:

• Between 4 and 18 years of age, inclusive

• Previous diagnosis of a posterior fossa brain tumor; patients who are either undergoing active treatment for posterior fossa tumor or who have completed treatment will be eligible for study enrollment

• Life expectancy of at least one year

• Able to understand and willing to consent assent to the research proposed, along with consent of legal guardian(s) if applicable

Exclusion Criteria:

• Presence of visual impairment to an extent that the patient is unable to complete the computer testing

• Contraindication to MRI scan (i.e. due to cardiac pacemaker)

Cohort 3 (20 patients will be enrolled to this cohort. This may include some or all of the patients enrolled to Cohort 1) Inclusion Criteria

• Between 4 and 18 years of age, inclusive

• Previous diagnosis of a posterior fossa brain tumor

• Clinical diagnosis of post-operative posterior fossa syndrome

• Inability to complete NIH Toolbox

• Life expectancy of at least one year

• Able to understand and willing to consent assent to the research proposed, along with consent of legal guardian(s) if applicable

Exclusion Criteria

• Contraindication to MRI scan (i.e. due to cardiac pacemaker)

Cohort 4 (50 Patients will be enrolled to Cohort 4. This will include patients previously enrolled on Cohorts 1-3 above.)

Inclusion Criteria

• Between 12-30 years of age, inclusive

• Diagnosis of a brain tumor >3 years prior to study enrollment

• Life expectancy of at least one year

• Able to understand and willing to consent assent to the research proposed, along with consent of legal guardian(s) if applicable

• Patient must be able to complete a 1 hour MRI scan without sedation

Exclusion Criteria

• Contraindiciation to MRI scan (i.e. due to cardian pacemaker)

• Presence of dental braces or programmable shunt

• Patient requires sedation for MRI scan

Related Conditions & MeSH terms

• Brain Neoplasms
• Childhood Brain Tumor

Intervention

Other:
• Neurocognitive testing

Device:
• rsfcMRI
The imaging protocols will be a combined version of a standard of care (SOC) protocol with a research portion. The SOC portion of the pre-surgical scans includes a 3D T2-weighted (T2w) scans and 3D pre- and post-contrast T1-weighted (T1w) images, both at high resolution (1.0 mm3) for use in the intraoperative navigation system. This scan also includes a DTI portion for definition of fiber bundles of interest. The SOC portion of the post-surgical scans includes transverse FLAIR and post-contrast T1w images in all 3 planes. The research portion of the scan will be identical at all 3 time points and include 15 min of rsfcMRI during which the non-sedated subjects will be asked to stay still and awake while looking at a fixation cross

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
Washington University School of Medicine	Children's Discovery Institute, Neurosurgery Research & Education Foundation, The Andrew McDonough B+ (Be Positive) Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identify reliable peri-diagnostic estimators of cognition as measured by neurocognitive testing		Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later)
Primary	Identify reliable peri-diagnostic estimators of cognition as measured by advanced resting-state functional connectivity MRI (rsfcMRI) data		Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later)
Primary	Predictors of cognitive recovery in children as determined by multiplexed analyses of a combination of potential biomarkers across multiple modalities (rsfcMRI, structural MRI, NIH Toolbox, patient demographics, treatment information)	As dictated by information theory, properly combining predictors across modalities must increase the accuracy of the prediction algorithm, unless a given modality contains no information about the question of interest (in this case, long-term cognitive outcomes).	Up to 27 months
Primary	Identify reliable peri-diagnostic estimators of brain function as measured by neurocognitive testing		Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later)
Primary	Identify reliable peri-diagnostic estimators of brain function as measured by advanced resting-state functional connectivity MRI (rsfcMRI) data		Peri-diagnostic period (from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later)

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine