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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ClinicalTrials.gov Identifier: NCT02372409 |
Recruitment Status :
Recruiting
First Posted : February 26, 2015
Last Update Posted : January 5, 2021
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Condition or disease | Intervention/treatment | Phase |
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Glioma Pilocytic Astrocytoma Anaplastic Astrocytoma Glioblastoma Mixed Oligoastrocytoma Mixed Glioma Oligodendroglioma Optic Glioma Astrocytoma | Device: MRI-guided laser ablation Drug: Doxorubicin Drug: Etoposide Device: Dynamic contrast-enhanced (DCE) MRI Device: Dynamic susceptibility contrast (DSC) MRI | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 12 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | August 14, 2015 |
Estimated Primary Completion Date : | October 30, 2021 |
Estimated Study Completion Date : | October 30, 2021 |

Arm | Intervention/treatment |
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Experimental: Arm A (MRI-guided laser ablation)
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Device: MRI-guided laser ablation
Other Name: MLA Device: Dynamic contrast-enhanced (DCE) MRI Other Name: DCE-MRI Device: Dynamic susceptibility contrast (DSC) MRI Other Name: DSC-MRI |
Experimental: Arm B (MRI-guided laser ablation, doxorubicin, etoposide)
|
Device: MRI-guided laser ablation
Other Name: MLA Drug: Doxorubicin Other Name: Adriamycin Drug: Etoposide Other Names:
Device: Dynamic contrast-enhanced (DCE) MRI Other Name: DCE-MRI Device: Dynamic susceptibility contrast (DSC) MRI Other Name: DSC-MRI |
- 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.
- 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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Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
- Recurrent pediatric brain tumors determined candidates for MLA as determined by the treating neurosurgeon.
- Unequivocal evidence of tumor progression by MRI
- There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between evidence of tumor recurrence and pseudoprogression.
- Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA.
- Age 3 to ≤ 21
- Karnofsky/Lansky performance status ≥ 60%
- Adequate cardiac function as determined by a shortening fraction ≥ 27% or left ventricular ejection fraction ≥ 50% by echocardiogram within the past 1 year prior to registration.
- Prior anthracycline therapy does not exceed 200 mg/m^2 total cumulative dose.
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Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):
- Absolute neutrophil count (ANC) ≥ 1000/mcl (G-CSF is allowed)
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9 g/dL (pRBC transfusion +/- ESA are allowed)
- ALT ≤ 3 x ULN
- AST ≤ 3 x ULN
- ALP ≤ 3 x ULN. If ALP is > 3 x ULN, GGT must be checked and be ≤ 3 x ULN.
- Bilirubin ≤ 2 x ULN
- At the time of registration, patient must have recovered from the toxic effects of prior therapy to no more than grade 1 toxicity.
- At the time of registration, patient must be at least 4 weeks from other prior cytotoxic chemotherapy.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
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.

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): NCT02372409
Contact: Joshua Rubin, M.D., Ph.D. | 314-286-2790 | rubin_j@wustl.edu |
United States, Missouri | |
Washington University School of Medicine | Recruiting |
Saint Louis, Missouri, United States, 63110 | |
Contact: Joshua Rubin, M.D., Ph.D. 314-286-2790 rubin_j@wustl.edu | |
Principal Investigator: Joshua Rubin, M.D., Ph.D. | |
Sub-Investigator: David Limbrick, M.D. | |
Sub-Investigator: Joshua Shimony, M.D., Ph.D. | |
Sub-Investigator: Gavin Dunn, M.D., Ph.D. | |
Sub-Investigator: Allison King, M.D., M.P.H. | |
Sub-Investigator: Eric Leuthardt, M.D. |
Principal Investigator: | Joshua Rubin, M.D., Ph.D. | Washington University School of Medicine |
Publications:
Responsible Party: | Washington University School of Medicine |
ClinicalTrials.gov Identifier: | NCT02372409 |
Other Study ID Numbers: |
201502062 |
First Posted: | February 26, 2015 Key Record Dates |
Last Update Posted: | January 5, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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 |
Glioblastoma Glioma Astrocytoma Oligodendroglioma Optic Nerve Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Nervous System Neoplasms Neoplasms by Site Nervous System Diseases |
Optic Nerve Neoplasms Cranial Nerve Neoplasms Peripheral Nervous System Neoplasms Cranial Nerve Diseases Optic Nerve Diseases Eye Diseases Doxorubicin Etoposide Etoposide phosphate Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |