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 Doxorubicin in the Treatment of Recurrent Glioblastoma Multiforme
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers
Study Overview
Brief Summary
This pilot clinical trial studies magnetic resonance imaging (MRI)-guided laser surgery (MLA) and doxorubicin hydrochloride in treating patients with recurrent glioblastoma multiforme. The blood brain barrier (BBB) is a separation of circulating blood from the tissue of the central nervous system, preventing substances in the blood from entering the brain. MLA disrupts the BBB around the tumor which may allow cancer-killing substances to be carried directly to the tumor and the surrounding area. Using MLA prior to chemotherapy may result in a greater concentration of drug in the tumor to kill the cancer cells while limiting side effects.
Detailed Description
Evaluate imaging techniques (MRI) and blood tests (biomarkers) to help figure out the best time for chemotherapy to be initiated after the blood brain barrier is disrupted, as it is immediately following a procedure like MRI-guided laser ablation (MLA-Monteris Neuroblate).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)
- Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.
- Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.
- Biomarker blood draws will be drawn at different time points.
- DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: MRI-guided Laser Heat Ablation (MLA) (Device)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)
- Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.
- Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.
- Biomarker blood draws will be drawn at different time points.
- DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: Doxorubicin (Drug)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)
- Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.
- Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.
- Biomarker blood draws will be drawn at different time points.
- DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: Blood draw - dendritic cells (Other)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)
- Patients undergo MLA (MRI-guided laser heat ablation). A subset of patients will have a biopsy at time of MLA.
- Beginning 6-8 weeks later, patients receive doxorubicin hydrochloride 20 mg/m2 intravenously (IV) over 5 minutes once weekly for 6 weeks.
- Biomarker blood draws will be drawn at different time points.
- DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: Dynamic Susceptibility Contrast Magnetic Resonance Imaging (Device)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)
-
Patients undergo MLA (MRI-guided laser heat ablation).
-
Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks.
-
DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: MRI-guided Laser Heat Ablation (MLA) (Device)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)
-
Patients undergo MLA (MRI-guided laser heat ablation).
-
Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks.
-
DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: Doxorubicin (Drug)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)
-
Patients undergo MLA (MRI-guided laser heat ablation).
-
Beginning within 72 hours later, patients receive doxorubicin hydrochloride 20 mg/m2 IV over 5 minutes once weekly for 6 weeks.
-
DSC-MRI: no more than 2 weeks prior to MLA, within approximately 3 days after MLA, 2/4/6 weeks after MLA, 10 weeks after MLA only if 6-week scan shows prolonged disruption of the blood brain barrier, 14 weeks after MLA only if week 10 MRI shows contined blood brain barrier disruption, and every 8 weeks until disease progression (these scans do not have to be DSC-MRI)
Intervention: Dynamic Susceptibility Contrast Magnetic Resonance Imaging (Device)
Outcomes
Primary Outcomes
Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers
Time Frame: 6 weeks
Pearson correlation coefficient (r) will be determined for each biomarker and Ktrans value. 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 to determine whether it has a predictive value.
6-month PFS (rate)
Time Frame: 6 months
Assessed using RANO Response criteria. A log-rank test will be used to compare 6-PFS of Arm B and of Arm C to historical controls.
Ktrans from DSC-MRI
Time Frame: 6 weeks
Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage
Secondary Outcomes
- Overall Survival(2 years)
- Quality of Life(2 years)