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NCT02372409

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

Terminated Phase 2 Results posted Last updated 1 November 2024
What this trial tests

Phase 2 trial testing MRI-guided laser ablation in Glioma in 6 participants. Terminated before completion.

Timeline
14 August 2015
Primary endpoint
23 March 2023
23 March 2023

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment6
Start date14 August 2015
Primary completion23 March 2023
Estimated completion23 March 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

Adults 3 to 21, any sex, with Glioma or Pilocytic Astrocytoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Arm A Only: Number of Participants With Progression-free Survival (PFS) Primary · Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)

PFS is followed from start of treatment to time of progression or death, whichever occurs first.

GroupValue95% CI
Arm A (MRI-guided Laser Ablation)4
Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years Primary · Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
GroupValue95% CI
Arm A (MRI-guided Laser Ablation)5
Arm B Only: Number of Participants With Progression-free Survival (PFS) Primary · At 6 months

PFS is followed from start of treatment to time of progression or death, whichever occurs first.

GroupValue95% CI
Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)0
Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status Secondary · At 1 year post-MLA

Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life.

Baseline
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)90
Patient 2: Arm A (MRI-guided Laser Ablation)100
Patient 3: Arm A (MRI-guided Laser Ablation)80
Patient 4: Arm A (MRI-guided Laser Ablation)100
Patient 5: Arm A (MRI-guided Laser Ablation)100
1 year post-MLA
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)90
Patient 2: Arm A (MRI-guided Laser Ablation)100
Patient 3: Arm A (MRI-guided Laser Ablation)80
Patient 4: Arm A (MRI-guided Laser Ablation)100
Patient 5: Arm A (MRI-guided Laser Ablation)100
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) Secondary · Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * Neuron specific enolase is an enzyme involved in glycolysis, which is localized in neurons and axonal processes. Potentially, it escapes into the blood and CSF at the time of neural injury. Elevated seru

Baseline
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)29.0219
Patient 4: Arm A (MRI-guided Laser Ablation)58.3406
Patient 3: Arm A (MRI-guided Laser Ablation)3.1823
Patient 5: Arm A (MRI-guided Laser Ablation)13.1819
Patient 6: Arm A (MRI-guided Laser Ablation)7.5534
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)11.5114
Day 3
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)47.2666
Patient 4: Arm A (MRI-guided Laser Ablation)26.7537
Patient 3: Arm A (MRI-guided Laser Ablation)6.0443
Patient 5: Arm A (MRI-guided Laser Ablation)33.8034
Patient 6: Arm A (MRI-guided Laser Ablation)17.4680
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)18.5711
1 week
GroupValue95% CI
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)11.5909
2 week
GroupValue95% CI
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)8.6069
2-4 weeks
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)12.0186
Patient 4: Arm A (MRI-guided Laser Ablation)53.2519
Patient 3: Arm A (MRI-guided Laser Ablation)5.4452
Patient 5: Arm A (MRI-guided Laser Ablation)11.4998
Patient 6: Arm A (MRI-guided Laser Ablation)9.3916
4 week
GroupValue95% CI
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)5.7440
12 weeks
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)105.7828
Patient 4: Arm A (MRI-guided Laser Ablation)15.1011
Patient 3: Arm A (MRI-guided Laser Ablation)7.5436
Patient 5: Arm A (MRI-guided Laser Ablation)206.8570
Patient 6: Arm A (MRI-guided Laser Ablation)13.5989
14 weeks
GroupValue95% CI
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)6.1692
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B Secondary · Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * S100b is a low-molecular-weight Calcium-binding protein primarily found in astrocytic glial cells of the CNS. It is secreted by astrocytes for neuroprotective and -trophic cellular functions in the CNS.

Baseline
GroupValue95% CI
Patient 4: Arm A (MRI-guided Laser Ablation)79.74
Day 3
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)39.90
Patient 4: Arm A (MRI-guided Laser Ablation)58.86
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)35.90
2-4 weeks
GroupValue95% CI
Patient 4: Arm A (MRI-guided Laser Ablation)55.74
12 weeks
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)156.00
Patient 4: Arm A (MRI-guided Laser Ablation)59.78
Patient 5: Arm A (MRI-guided Laser Ablation)239.13
24 weeks
GroupValue95% CI
Patient 4: Arm A (MRI-guided Laser Ablation)65.91
36 weeks
GroupValue95% CI
Patient 4: Arm A (MRI-guided Laser Ablation)55.66
48 weeks
GroupValue95% CI
Patient 4: Arm A (MRI-guided Laser Ablation)79.11
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP Secondary · Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)

* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * The glial fibrillary acidic protein (GFAP) is a classic intermediate filament protein specific to astrocytes in the CNS. GFAP is characteristic of astrocyte- and neural stem cell-derived gliomas in CNS t

Day 3
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)4.7370968
Patient 3: Arm A (MRI-guided Laser Ablation)1.6146649
Patient 5: Arm A (MRI-guided Laser Ablation)0.2225989
Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)5.6051762
2-4 weeks
GroupValue95% CI
Patient 1: Arm A (MRI-guided Laser Ablation)0.0652591

Adverse events — posted to ClinicalTrials.gov

Time frame: -Reportable adverse events will be tracked for 30 days following the last day of study treatment for patients in Arm B and for 30 days following the MLA for patients in Arm A. -All-cause mortality will be collected from start of treatment up to 5 years after start of treatment (median length of follow-up 413.5 days, full range 366 days-1801 days).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A (MRI-guided Laser Ablation)
Serious: 0/5 (0%)
Deaths: 0/5
Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide)
Serious: 0/1 (0%)
Deaths: 0/1
Other adverse events (7 terms — click to expand)

ReactionSystemArm A (MRI-guided Laser Ab…Arm B (MRI-guided Laser Ab…
Fecal incontinenceGastrointestinal disorders
FatigueGeneral disorders
HeadacheNervous system disorders
ParesthesiaNervous system disorders
Memory impairmentNervous system disorders
ConfusionPsychiatric disorders
Noise sensitiveSocial circumstances

Data from ClinicalTrials.gov NCT02372409 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
    Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
  2. Laser ablation: Heating up the anti-tumor response in the intracranial compartment.
    Lerner EC, Edwards RM, Wilkinson DS, Fecci PE. · · 2022 · cited 50× · PMID 35489652 · DOI 10.1016/j.addr.2022.114311
  3. The effect of thermal therapy on the blood-brain barrier and blood-tumor barrier.
    Patel B, Yang PH, Kim AH. · · 2020 · cited 45× · PMID 32672118 · DOI 10.1080/02656736.2020.1783461
  4. Thermal Therapy Approaches for Treatment of Brain Tumors in Animals and Humans.
    Bredlau AL, McCrackin MA, Motamarry A, Helke K, et al · · 2016 · cited 27× · PMID 29431091 · DOI 10.1615/critrevbiomedeng.2017021249
  5. Ribosomal protein S11 influences glioma response to TOP2 poisons.
    Awah CU, Chen L, Bansal M, Mahajan A, et al · · 2020 · cited 24× · PMID 32528131 · DOI 10.1038/s41388-020-1342-0
  6. A systematic review of ongoing clinical trials in optic pathway gliomas.
    Hill CS, Devesa SC, Ince W, Borg A, et al · · 2020 · cited 19× · PMID 32556546 · DOI 10.1007/s00381-020-04724-1
  7. Device-assisted strategies for drug delivery across the blood-brain barrier to treat glioblastoma.
    Mokarram N, Case A, Hossainy NN, Lyon JG, et al · · 2025 · cited 17× · PMID 39790893 · DOI 10.1038/s43246-024-00721-y
  8. Laser application in neurosurgery.
    Belykh E, Yagmurlu K, Martirosyan NL, Lei T, et al · · 2017 · cited 17× · PMID 29204309 · DOI 10.4103/sni.sni_489_16

Verify or expand the search:

Other trials of MRI-guided laser ablation

Trials testing the same drug.

Other recruiting trials for Glioma

Currently open trials in the same condition.

Other Washington University School of Medicine trials

Trials by the same sponsor.

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