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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Glioblastoma
Intervention	Other: Blood draw - biomarkers Procedure: MRI-guided Laser Heat Ablation (MLA) Drug: Doxorubicin
Phase	N/A
Sponsor	Washington University School of Medicine
Responsible Party	Washington University School of Medicine
ClinicalTrials.gov Identifier	NCT01851733
First Received	May 7, 2013
Last Updated	February 11, 2014
Last verified	February 2014

Tracking Information[ + expand ][ + ]

First Received Date	May 7, 2013
Last Updated Date	February 11, 2014
Start Date	August 2013
Estimated Primary Completion Date	December 2017
Current Primary Outcome Measures	Ktrans from DSC-MRI [Time Frame: 6 weeks] [Designated as safety issue: No]Using a 2 compartment model to calculate a the vascular transfer constant (Ktrans) which will provide a quantitative measure of blood brain barrier leakage Peritumoral permeability scores, measured by DSC-MRI and serum biomarkers [Time Frame: 6 weeks] [Designated as safety issue: No]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] [Designated as safety issue: No]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.
Current Secondary Outcome Measures	Overall Survival [Time Frame: 2 years] [Designated as safety issue: No]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 [Time Frame: 2 years] [Designated as safety issue: No]Using Karnofsky performance status and the mini-mental state evaluation to assess patient overall response to treatment.

Descriptive Information[ + expand ][ + ]

Brief Title	MRI-Guided Laser Surgery and Doxorubicin Hydrochloride in Treating Patients With Recurrent Glioblastoma Multiforme
Official Title	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
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 Type	Interventional
Study Phase	N/A
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Condition	Glioblastoma
Intervention	Other: Blood draw - biomarkers Immediately before biopsy/MLA (Arms A, B, C) Approximately 24 hours after biopsy/MLA (Arms A, B, C) 1-2 weeks after biopsy (Arm A) Weekly for 6 weeks (Arm B) Weekly immediately before chemotherapy (Arm C) Weekly approximately 24 hours after chemotherapy (Arm C) 10 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the blood brain barrier (Arms B and C) 14 weeks after MLA ONLY IF the 6-week post-MLA scan shows prolonged disruption of the blood brain barrier (Arms B and C) Procedure: MRI-guided Laser Heat Ablation (MLA) Drug: Doxorubicin Other Names: Adriamycin®
Study Arm (s)	Other: Arm A: Control Patients undergo biopsy per standard of care diagnostic purposes. Biomarker blood draws will be drawn at different time points. Experimental: Arm B: (MLA, doxorubicin hydrochloride at 6-8 weeks) Patients undergo MLA (MRI-guided laser heat ablation). 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. Experimental: 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. Biomarker blood draws will be drawn at different time points.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	45
Estimated Completion Date	December 2017
Estimated Primary Completion Date	December 2015
Eligibility Criteria	Inclusion Criteria - Arm A: - Newly diagnosed brain tumors that appear high-grade based on MRI. - Scheduled for biopsy for diagnostic purposes. - At least 18 years of age. - Ability to understand and willingness to sign an IRB-approved written informed consent document. Exclusion Criteria - Arm A: - Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed high grade glioma prior to the biopsy and the post-biopsy biomarker sample collection. - Pregnant. Inclusion Criteria - Arms B and C: - Histologically confirmed GBM; rare GBM variants and secondary Glioblastoma multiforme (GBM) are allowed. Note: Patients with suspected secondary GBM will be eligible to consent to this study. The biopsy for pathologic confirmation of secondary GBM is typically performed at the same time as the MLA procedure to minimize risk to patients (one surgical procedure to the brain instead of two). These patients would be consented and would undergo study procedures (the pre- and post-MLA blood draws and MRIs), but would not go on to receive doxorubicin if pathology does not confirm the diagnosis of secondary GBM. For these patients, confirmation of secondary GBM from frozen tissue or preliminary pathology is acceptable in the absence of full pathology for randomization and treatment. - 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. - Largest dimension of the recurrent tumor is a maximum of approximately 3 cm. - 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. - 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 2 weeks from prior vincristine, 3 weeks from prior procarbazine, and 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 - Arms B and C: - 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 HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with doxorubicin. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: David Tran, M.D., Ph.D. 314-362-5677 dtran@dom.wustl.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01851733
Other Study ID Numbers	201305148
Has Data Monitoring Committee	No
Information Provided By	Washington University School of Medicine
Study Sponsor	Washington University School of Medicine
Collaborators	Not Provided
Investigators	Principal Investigator: David Tran, M.D., Ph.D. Washington University School of Medicine
Verification Date	February 2014

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