A Study of the Specificity and Sensitivity of 5-ALA Fluorescence in Malignant Brain Tumors
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 and 2 Study of 5-aminolevulinic Acid (5-ALA) to Enhance Visualisation and Resection of Malignant Glial Tumors of the Brain|
- Establish a safe dose for oral 5-ALA administration. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Determine the sensitivity and specificity of 5-ALA mediated fluorescence for malignant glioma tissue in the brain [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
- Compare the neurosurgeon's intra-operative estimate of the extent of malignant glioma resection (as guided by tumor fluorescence) with the actual extent of resection determined by post-operative imaging [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Compare time-to-progression and survival to that in comparable cases performed without the aid of 5-ALA [ Time Frame: 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Experimental: Tumor fluorescence
A single arm in this open-label study where all patients are treated with the study drug. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells
Drug: 5-aminolevulinic acid
oral doses in phase 1 study of 10mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00977795
|Principal Investigator:||Jeffrey W. Cozzens, M.D.||NorthShore University HealthSystem|