5-ALA in Recurrent Glioma
5-ALA in Recurrent Glioma
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.
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:

 1. To determine the impact of the dose of 5-ALA in improving volumetric extent of resection
 in patients with recurrent high grade gliomas

 2. To determine the impact of the dose of 5-ALA in improving overall survival of recurrent
 high grade glioma patients

 3. To determine the impact of the dose of 5-ALA in improving progression-free survival of
 recurrent high grade glioma patients

 4. 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.
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