MRI-Guided Laser Surgery and Doxorubicin Hydrochloride in Treating Patients With Recurrent Glioblastoma Multiforme

Phase 1

Completed

• Conditions: Glioblastoma
• Interventions: Device: MRI-guided Laser Heat Ablation (MLA); Drug: Doxorubicin; Other: Blood draw - dendritic cells; Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging

• Registration Number: NCT01851733
• Lead Sponsor: Washington University School of Medicine

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 Timeline

• Study First Submitted: 2013-05-07
• Study First Submitted QC: 2013-05-07
• Study First Posted: 2013-05-10
• Study Start: 2013-08-13
• Primary Completion: 2018-04-12
• Study Completion: 2018-05-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-26
• Last Update Posted: 2021-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)	Dynamic Susceptibility Contrast Magnetic Resonance Imaging	* 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)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)	MRI-guided Laser Heat Ablation (MLA)	* 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)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)	Blood draw - dendritic cells	* 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)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)	Dynamic Susceptibility Contrast Magnetic Resonance Imaging	* 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)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)	MRI-guided Laser Heat Ablation (MLA)	* 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)
Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)	Doxorubicin	* 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)
Arm C: (MLA, doxorubicin hydrochloride at 72 hours)	Doxorubicin	* 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)

Primary Outcome Measures

Name	Time	Method
Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers	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)	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	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 Outcome Measures

Name	Time	Method
Overall Survival	2 years	Date began MLA treatment to date of death from any cause. A log-rank test will be used to compare OS of Arm B and of Arm C to historical controls.
Quality of Life	2 years	Using Karnofsky performance status and the mini-mental state evaluation to assess patient overall response to treatment.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States