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

NCT01851733 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 201305148
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Ktrans from DSC-MRI

  Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage

  6 weeks

• Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers

  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 weeks

• 6-month PFS (rate)

  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.

  6 months

Secondary Outcomes (2)

• Overall Survival

  2 years

• Quality of Life

  2 years

Study Arms (2)

Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)

EXPERIMENTAL

* 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)

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

Arm C: (MLA, doxorubicin hydrochloride at 72 hours)

EXPERIMENTAL

* 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)

Device: MRI-guided Laser Heat Ablation (MLA); Drug: Doxorubicin; Device: Dynamic Susceptibility Contrast Magnetic Resonance Imaging

Interventions

MRI-guided Laser Heat Ablation (MLA) DEVICE

Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks); Arm C: (MLA, doxorubicin hydrochloride at 72 hours)

Doxorubicin DRUG

Also known as: Adriamycin®

Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks); Arm C: (MLA, doxorubicin hydrochloride at 72 hours)

Blood draw - dendritic cells OTHER

The second 10 patients enrolled to Arm B: * before MLA (up to 3 days before) * 2 weeks after MLA * 4 weeks after MLA * every 2 weeks thereafter for up to 3 months after biopsy (provided there is no significant chemotherapy induced cytopenia)

Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks)

Dynamic Susceptibility Contrast Magnetic Resonance Imaging DEVICE

Also known as: DSC-MRI

Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks); Arm C: (MLA, doxorubicin hydrochloride at 72 hours)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed GBM; rare GBM variants, secondary GBM, and suspected secondary GBM are allowed.
• Unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) scan.
• 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 unequivocal evidence of tumor recurrence and pseudoprogression.
• Candidate for MLA based on size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon
• At least 18 years of age.
• Karnofsky performance status ≥ 60%.
• Scheduled for MRI-guided Laser Ablation (MLA).
• Normal left ventricular ejection fraction on MUGA or echocardiogram within the past 1 year prior to registration for patients with history of congestive heart failure and/or coronary disease requiring medications other than aspirin, or known prior exposure to anthracycline chemotherapy.
• Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA):
• Absolute neutrophil count (ANC) ≥ 1500/mcl (G-CSF is allowed)
• Platelets ≥ 100,000/mcl
• Hemoglobin ≥ 9 (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.

You may not qualify if:

• Prior treatment with doxorubicin and/or bevacizumab.
• Prior treatment with Gliadel wafer is allowed if it has been at least 3 months from placement.
• Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of 240 mg/m2 doxorubicin.
• More than 2 prior relapses.
• Currently receiving any other investigational agents that are intended as treatments of GBM.
• 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 pregnancy test within 14 days of study entry.
• Inability to undergo MRI due to personal and medical reasons.
• Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Leuthardt EC, Duan C, Kim MJ, Campian JL, Kim AH, Miller-Thomas MM, Shimony JS, Tran DD. Hyperthermic Laser Ablation of Recurrent Glioblastoma Leads to Temporary Disruption of the Peritumoral Blood Brain Barrier. PLoS One. 2016 Feb 24;11(2):e0148613. doi: 10.1371/journal.pone.0148613. eCollection 2016.

  PMID: 26910903 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioblastoma

Interventions

Doxorubicin; Perfusion Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Milan Chheda, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2013
• First Posted: May 10, 2013
• Study Start: August 13, 2013
• Primary Completion: April 12, 2018
• Study Completion: May 30, 2018
• Last Updated: August 27, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)