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