February 13, 2015
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February 26, 2015
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January 5, 2021
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August 14, 2015
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October 30, 2021 (Final data collection date for primary outcome measure)
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- 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.
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Same as current
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- 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.
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Same as current
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Not Provided
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Not Provided
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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
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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
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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.
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Not Provided
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Interventional
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Phase 2
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Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Glioma
- Pilocytic Astrocytoma
- Anaplastic Astrocytoma
- Glioblastoma
- Mixed Oligoastrocytoma
- Mixed Glioma
- Oligodendroglioma
- Optic Glioma
- Astrocytoma
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- Device: MRI-guided laser ablation
Other Name: MLA
- Drug: Doxorubicin
Other Name: Adriamycin
- Drug: Etoposide
Other Names:
- Etoposide phosphate
- VP-16
- Toposar
- Etopophos
- VePesid
- Device: Dynamic contrast-enhanced (DCE) MRI
Other Name: DCE-MRI
- Device: Dynamic susceptibility contrast (DSC) MRI
Other Name: DSC-MRI
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- Experimental: Arm A (MRI-guided laser ablation)
Interventions:
- Device: MRI-guided laser ablation
- Device: Dynamic contrast-enhanced (DCE) MRI
- Device: Dynamic susceptibility contrast (DSC) MRI
- Experimental: Arm B (MRI-guided laser ablation, doxorubicin, etoposide)
Interventions:
- Device: MRI-guided laser ablation
- Drug: Doxorubicin
- Drug: Etoposide
- Device: Dynamic contrast-enhanced (DCE) MRI
- Device: Dynamic susceptibility contrast (DSC) MRI
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- Holodny AI, Nusbaum AO, Festa S, Pronin IN, Lee HJ, Kalnin AJ. Correlation between the degree of contrast enhancement and the volume of peritumoral edema in meningiomas and malignant gliomas. Neuroradiology. 1999 Nov;41(11):820-5.
- Kassner A, Thornhill R. Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Methods Mol Biol. 2011;686:229-45. doi: 10.1007/978-1-60761-938-3_10.
- Hawasli AH, Ray WZ, Murphy RK, Dacey RG Jr, Leuthardt EC. Magnetic resonance imaging-guided focused laser interstitial thermal therapy for subinsular metastatic adenocarcinoma: technical case report. Neurosurgery. 2012 Jun;70(2 Suppl Operative):332-7; discussion 338. doi: 10.1227/NEU.0b013e318232fc90.
- Gong W, Wang Z, Liu N, Lin W, Wang X, Xu D, Liu H, Zeng C, Xie X, Mei X, Lü W. Improving efficiency of adriamycin crossing blood brain barrier by combination of thermosensitive liposomes and hyperthermia. Biol Pharm Bull. 2011;34(7):1058-64.
- Quick J, Gessler F, Dützmann S, Hattingen E, Harter PN, Weise LM, Franz K, Seifert V, Senft C. Benefit of tumor resection for recurrent glioblastoma. J Neurooncol. 2014 Apr;117(2):365-72. doi: 10.1007/s11060-014-1397-2. Epub 2014 Feb 15.
- Ashley DM, Meier L, Kerby T, Zalduondo FM, Friedman HS, Gajjar A, Kun L, Duffner PK, Smith S, Longee D. Response of recurrent medulloblastoma to low-dose oral etoposide. J Clin Oncol. 1996 Jun;14(6):1922-7.
- Davidson A, Gowing R, Lowis S, Newell D, Lewis I, Dicks-Mireaux C, Pinkerton CR. Phase II study of 21 day schedule oral etoposide in children. New Agents Group of the United Kingdom Children's Cancer Study Group (UKCCSG). Eur J Cancer. 1997 Oct;33(11):1816-22.
- Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996 Feb;27(2):149-55.
- Law M, Young R, Babb J, Rad M, Sasaki T, Zagzag D, Johnson G. Comparing perfusion metrics obtained from a single compartment versus pharmacokinetic modeling methods using dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade. AJNR Am J Neuroradiol. 2006 Oct;27(9):1975-82.
- Blyth BJ, Farhavar A, Gee C, Hawthorn B, He H, Nayak A, Stöcklein V, Bazarian JJ. Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma. 2009 Sep;26(9):1497-1507. doi: 10.1089/neu.2008-0738.
- Dunn GP, Dunn IF, Curry WT. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007 Aug 13;7:12. Review.
- Dunn GP, Fecci PE, Curry WT. Cancer immunoediting in malignant glioma. Neurosurgery. 2012 Aug;71(2):201-22; discussion 222-3. doi: 10.1227/NEU.0b013e31824f840d. Review.
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Recruiting
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12
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Same as current
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October 30, 2021
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October 30, 2021 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
ARM A
- Presumed pediatric gliomas (grades I-IV) on MRI that are determined to be candidates for MLA by the treating neurosurgeon
- Age 3 to ≤ 21
- Karnofsky/Lansky performance status ≥ 60%
ARM B
Exclusion Criteria:
ARM A
- Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed glioma prior to MLA and the first post-MLA blood collection for correlative studies.
- Multi-focal or metastatic disease.
- Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine pregnancy test within 14 days of study entry.
- Inability to undergo MRI due to personal or medical reasons.
- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.
ARM B
- Prior treatment with bevacizumab within 12 weeks of study entry.
- Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of > 200 mg/m2 doxorubicin.
- More than 2 prior relapses (not counting the current relapse being treated on this study).
- Currently receiving any other investigational agents that are intended as treatments of the relapsed tumor.
- Multi-focal or metastatic disease.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent heart attack within the previous 12 months or severe heart problems, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine pregnancy test within 14 days of study entry.
- Inability to undergo MRI due to personal or medical reasons.
- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.
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Sexes Eligible for Study: |
All |
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3 Years to 21 Years (Child, Adult)
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No
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United States
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NCT02372409
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201502062
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
Yes |
Product Manufactured in and Exported from the U.S.: |
No |
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Washington University School of Medicine
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Washington University School of Medicine
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Not Provided
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Principal Investigator: |
Joshua Rubin, M.D., Ph.D. |
Washington University School of Medicine |
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Washington University School of Medicine
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January 2021
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