MRI-Guided Laser Heat Ablation in Treating Younger Patients with Brain Tumors
This pilot phase II trial studies magnetic resonance imaging (MRI)-guided laser heat ablation in treating younger patients with brain tumors. MRI-guided laser ablation (MLA) is a minimally invasive laser surgery that uses a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation. MLA may disrupt the blood brain barrier, a separation of circulating blood from the fluid of the nervous system, which may improve delivery of the chemotherapy drugs to the brain.
Inclusion 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
- ARM A AND ARM B Age 3 to =< 21
- Karnofsky/Lansky performance status >= 60%
- INCLUSION CRITERIA - 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 Response Assessment in Neuro-Oncology (RANO) criteria; when the interval is less than 12 weeks from the completion of radiotherapy, the use of positron emission tomography (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
- Karnofsky/Lansky performance status >= 60% (Arm B)
- 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
- Absolute neutrophil count (ANC) >= 1000/mcl (granulocyte-colony stimulating factor [G-CSF] is allowed) (must be within 7 days of MLA)
- Platelets >= 100 K/cumm (must be within 7 days of MLA)
- Hemoglobin >= 9 g/dL (packed red blood cell [pRBC] transfusion +/- erythropoiesis-stimulating agents [ESA] are allowed) (must be within 7 days of MLA)
- Alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) (must be within 7 days of MLA)
- Aspartate aminotransferase (AST) =< 3 x ULN (must be within 7 days of MLA)
- Alkaline phosphatase (ALP) =< 3 x ULN; if ALP is > 3 x ULN, gamma glutamyltransferase (GGT) must be checked and be =< 3 x ULN (must be within 7 days of MLA)
- Bilirubin =< 2 x ULN (must be within 7 days of MLA)
- 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 institutional review board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
Exclusion Criteria
- EXCLUSION CRITERIA - ARM A:
- Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed glioma prior to the 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 human immunodeficiency virus (HIV) or autoimmune diseases requiring immunosuppressant drugs
- EXCLUSION CRITERIA - 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/m^2 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 (Arm B)
- 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 (Arm B)
- Inability to undergo MRI due to personal or medical reasons (Arm B)
- Known history of HIV or autoimmune diseases requiring immunosuppressant drugs
Additional locations may be listed on ClinicalTrials.gov for NCT02372409.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine progression-free survival (PFS) and overall survival (OS) of patients with new diagnosis glioma who are candidates for MLA (Arm A).
II. To determine 6-month progression-free survival (6PFS) in patients who receive doxorubicin immediately following MLA and low-dose etoposide as maintenance therapy in patients who are candidates for MLA with any type relapsed malignant brain tumors (Arm B).
III. To evaluate quality of life (QOL) using Karnofsky or Lansky performance status in patients following MLA and in patients who receive doxorubicin and maintenance etoposide after MLA.
SECONDARY OBJECTIVES:
I. To determine MR imaging correlates of peritumoral blood brain barrier (BBB) disruption after MLA.
II. To identify serum biomarkers of peritumoral BBB disruption after MLA, which can be used to establish peritumoral permeability scores.
III. To determine the predictive value of the peritumoral permeability score for patient outcome as measured by 6PFS rate.
EXPLORATORY OBJECTIVE:
I. To determine the effects of MLA treatment on patient’s tumor-specific immune responses and immunological correlates.
OUTLINE: Patients are assigned to 1 of 2 treatment arms.
ARM A: Patients undergo MLA followed by standard of care therapy at the discretion of the treating physician.
ARM B: Patients undergo MLA followed by doxorubicin hydrochloride intravenously (IV) over 5-30 minutes weekly for 6 weeks and then etoposide orally (PO) on days 1-21. Treatment with etoposide repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, every 12 weeks for 1 year and then every 6 months for 4 years (Arm A) or every 8-12 weeks for 2 years, and then every 6 months for 5 years (Arm B).
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorAndrew Stephen Cluster
- Primary ID201502062
- Secondary IDsNCI-2015-00403
- ClinicalTrials.gov IDNCT02372409