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 Purpose

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.

Recruitment Criteria

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Accepts Healthy Volunteers
No

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Study Type
Interventional
Eligible Ages 3 Years - 21 Years
Gender All
More Inclusion & Exclusion Criteria

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.
  • - 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.

Trial Details

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

Trial ID:
NCT02372409

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase
Phase 1

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Lead Sponsor
Washington University School of Medicine

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator
Karen Gauvain, M.D.
Principal Investigator Affiliation Washington University School of Medicine

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Agency Class
Other
Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Conditions
Glioma, Pilocytic Astrocytoma, Anaplastic Astrocytoma, Glioblastoma, Mixed Oligoastrocytoma, Mixed Glioma, Oligodendroglioma, Optic Glioma, Astrocytoma
Study Website: View Trial Website

Contact a Trial Team

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Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Karen Gauvain, M.D.

gauvaink@wustl.edu

314-454-4457

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