5-ALA in Recurrent Glioma

Study Overview
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Brief Summary
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The investigators propose a single-center, non-randomized, single-arm study at the Barrow Neurological Institute/St. Joseph's Hospital for recurrent glioma. The 5-ALA for recurrent glioma study will correlate presence of fluorescence in tumor tissue with pathological findings. This will be done using three cohorts in dose escalation. The investigators' hypothesis is that (for both low- and high-grade gliomas,) a lower dose of 5-ALA will result in less false positive fluorescence.

Detailed Description
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The goal is to determine the dose of 5-ALA which promotes the lowest volume of residual disease after resection of recurrent high grade glioma without compromising the demarcation between recurrent high grade glioma and postoperative bed normal tissue. Sub-goals: To determine the impact of the dose of 5-ALA in improving volumetric extent of resection in patients with recurrent high grade gliomas To determine the impact of the dose of 5-ALA in improving overall survival of recurrent high grade glioma patients To determine the impact of the dose of 5-ALA in improving progression-free survival of recurrent high grade glioma patients To determine the impact of the dose of 5-ALA on the neurological morbidity of recurrent high grade glioma patients. Patients with presumed recurrent glioma will be entered into the trial. Those with recurrent disease will receive study drug (5-ALA) in one of three dose-escalated cohorts (5 mg/kg; 10 mg/kg; 20 mg/kg). Intraoperatively, patients will undergo resection with combined fluorescence microscopy and confocal microscopy. Resected tissue specimens corresponding to the presence of fluorescence will be sent to pathology for examination. Postoperatively, patients will have an MRI with and without contrast within 48 hours of surgery. Subsequent analysis of each patient will include assessment of the primary endpoint (volume of residual disease) by volumetrically quantifying the tumor before and after surgery using T1-weighted contrast-enhancement. Similarly, volumetric extent of resection will also be measured.

Official Title
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Barrow ALA Trial for Recurrent Gliomas

Conditions
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Glioma

Intervention / Treatment
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* Drug: 5-ala


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Presumed recurrent glioma Age > 18 years Normal bone marrow function (WBC > 3000, Platelets > 100,000) Exclusion Criteria Pregnancy History of photosensitivity, porphyria, or exfoliative dermatitis Hepatic dysfunction in the last 12 months [defined by aspartate aminotransferase(AST), alanine aminotransferase (ALT) , alkaline phosphatase (ALP) , bilirubin > 2.5 x normal] Serum creatinine > 180 µmol/L Estimated Glomerular Filtration Rate (eGFR)< 60 ml/min/1.73m2 Inability to undergo MRI with contrast

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-ala preoperatively<br>A dose of 5-ala will be taken by mouth approximately 3 hours before going to surgery. | Drug: 5-ala<br>* dose of 5-ala will be taken as either 5 mg/kg, 10 mg/kg, or 20 mg/kg approximately 3 hours before going to surgery.<br>* Other names: Levulin(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of fluorescence in tumor tissue compared to tissue with treatment effect. | Correlation of fluorescence with pathological findings | day of surgery-1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of resection | A postoperative MRI with contrast will be acquired within 48 hours of surgery. Volumetric analysis of contract T1-weighted images (for low grade gliomas) will be compared to the preoperative sequences to calculate the volume of residual disease. Slice-by-slice assessment of pre- and postoperative tumor volume will be quantified by sequentially measuring the area of tumor on each slice and then integrating the combined measurements. This methodology has been previously reported (Sanai et al., Journal of Neurosurgery, 2010; Sanai et al, The New England Journal of Medicine, 2008) | time within 48 hours post operative | 
| Progression-free survival rate at 6 months |  | time from date of surgery to 6 months post surgery | 
| Overall survival |  | time from date of surgery to date of death from any cause, assessed up to 100 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-ala, 5-aminolevulinic acid, fluorescence-guided surgery, glioma, astrocytoma, glioblastoma, oligodendroglioma, recurrence of glioma