A Study of the Specificity and Sensitivity of 5-ALA Fluorescence in Malignant Brain Tumors

Summary

Extent of resection is a very important prognostic factor affecting survival in individuals diagnosed with a malignant glioma. However, the infiltrative nature of the malignant glioma tumor cells produces indistinct borders between normal and malignant tissues, and the lack of easily identifiable tumor margins confounds attempts at total resection. The investigators propose to identify the borders of malignant gliomas intraoperatively using oral 5-aminolevulinic Acid (5-ALA) which results in fluorescence of the malignant cells and thereby provide an opportunity for more complete tumor resection. When exogenous 5-ALA is provided at increased concentration the tumor cells will become fluorescent under ultraviolet light. This feature identifies the tumor cells intraoperatively and facilitates complete resection. The following data will be collected: * Dose-limiting toxicity data * Tumor fluorescence assessed by neurosurgeon (0 to +++) in three distinct areas of fluorescence (Strong fluorescence, Weak fluorescence, No fluorescence) * Tumor density from biopsies obtained by the neurosurgeon in the same three distinct areas of fluorescence and assessed by neuropathology (Solid tumor, Tumor mixed infiltrating normal brain, No tumor) * Neurosurgeon's intra-operative estimate of residual tumor * Neuroradiologist's estimate of post-operative residual tumor on MRI * Time to progression by MRI * Survival (time to progression, one year survival rate and total survival This trial will evaluate: * The toxicity of a single dose of oral 5-ALA given pre-operatively. * The sensitivity and specificity of 5-ALA - Protoporphyrin IX (Pp IX) as an intraoperative fluorescent detection agent and aid for resection of tumor tissue remaining in the walls of the resection cavity of primary and recurrent malignant brain tumors. * The relationship of the neurosurgeon's estimate of the extent of malignant glioma resection (as guided by tumor fluorescence) to the actual extent of resection determined by post-operative imaging. * The time-to-progression, one year survival rate and total survival as a function of the extent of resection. Following completion of the phase 1 portion of this trial, an additional 15 subjects will be entered at the recommended phase 2 dose level in order to further define the above parameters at the recommended phase 2 dose level.

Timeline

Start

2009-09

Primary completion

2010-01

Completion

2010-01

Publications

• Background Keles GE, Anderson B, Berger MS. The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg Neurol. 1999 Oct;52(4):371-9. doi: 10.1016/s0090-3019(99)00103-2.
• Background Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008 Apr;62(4):753-64; discussion 264-6. doi: 10.1227/01.neu.0000318159.21731.cf.
• Background Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9.
• Background Tonn JC, Stummer W. Fluorescence-guided resection of malignant gliomas using 5-aminolevulinic acid: practical use, risks, and pitfalls. Clin Neurosurg. 2008;55:20-6. No abstract available.

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