A Study of the Specificity and Sensitivity of 5-ALA Fluorescence in Malignant Brain Tumors
Status:
Withdrawn
Trial end date:
2010-01-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
NorthShore University HealthSystem NorthShore University HealthSystem Research Institute