Clinical Trial: Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Pilot Study of Using MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors

Brief Summary: By employing a combination of advanced MRI techniques and correlative serum biomarkers of blood brain barrier (BBB) disruption, the investigators plan to develop a powerful, first of its kind clinical algorithm in pediatrics whereby the investigators can measure and identify the window of maximal BBB disruption post MLA to 1) allow for an alternative to surgery in incompletely resected tumors, 2) allow for optimal chemotherapeutic dosing to achieve the greatest benefits and the least systemic side effects and 3) distinguish subsequent tumor progression from long-term MLA treatment effects. Preliminary data in adult imaging studies have shown that the BBB disruption lasts for several weeks following treatment before returning to a low baseline. This pilot therapeutic study will provide preliminary validation in pediatric patients.

Detailed Summary:
Sponsor: Washington University School of Medicine

Current Primary Outcome:

  • Arm A only: Progression-free survival (PFS) [ Time Frame: Up to 5 years ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
  • Arm A only: Overall survival (OS) [ Time Frame: Up to 5 years ]
  • Arm B only: Progression-free survival (PFS) [ Time Frame: 6 months ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
  • Arm B only: Quality of life (QOL) [ Time Frame: 1 year from MLA ]
    -Using Karnofsky or Lansky performance status in patients following MLA and in patients who receive doxorubicin and maintenance etoposide after MLA.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Correlation of MR imaging with peritumoral BBB disruption [ Time Frame: 1 year from MLA ]
    The linear regression model will used to investigate the correlation between MR imaging and peritumoral BBB disruption. To account for correlation among the repeated measures from the same patient, the longitudinal data will be analyzed with the use of linear generalized estimating equation (GEE). Whether the average measurements differ at the multiple time points will be evaluated through GEE model. Least-square means at each time points will be presented and standard errors will be calculated within the use of the GEE sandwich method when accounting for within-patient correlation.
  • Serum biomarkers of peritumoral BBB disruption [ Time Frame: 1 year from MLA ]
    Since the investigators do not know which biomarkers will have better correlation with the Ktrans data from DCE and DSC-MRI and patients' survival outcome, the investigators plan to determine the levels of all 3 biomarkers in a blinded fashion. Once both the Ktrans and biomarker levels are available, the investigators will determine which biomarkers have the closest correlation that is statistically significant with the Ktrans. Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority.
  • Predictive value of the peritumoral permeability score for patient outcome as measured by PFS [ Time Frame: 6 months ]
    Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data (as measured by 6 month PFS rate) to determine whether it has a predictive value.


Original Secondary Outcome: Same as current

Information By: Washington University School of Medicine

Dates:
Date Received: February 13, 2015
Date Started: August 14, 2015
Date Completion: October 30, 2019
Last Updated: March 3, 2017
Last Verified: March 2017