Fluorescence-Guided Detection of Malignant Gliomas: A Dose Ranging Study Using 5-Aminolevulinic Acid (ALA) Induced Protoporphyrin (PpIX) in a Multicenter Phase II Clinical Trial
OBJECTIVES:
Primary
- Assess 2 doses of 5-ALA, 10kg/mg and 20kg/mg, to determine the optimum ALA dose in
terms of both sensitivity and specificity for residual tumor. We will compare residual
tumor detection by both in vivo qualitative and quantitative fluorescence imaging using
histology of the biopsied tissue as the gold standard.
Secondary
- Assess the correlation between the recorded in vivo qualitative assessment of
fluorescence signal from the neurosurgeon with the post-surgical (i.e., ex vivo)
absolute PpIX concentration detected both intraoperatively and in ex vivo tissue
biopsies.
Tertiary
- To determine the association between the presence of fluorescence in the surgical
cavity and the post-operative image enhancement on MRI. This includes the relationship
between the amount and location of residual tumor detected by fluorescence, PpIX
concentration, and intra-operative frameless stereotaxy following maximal resection
versus the amount and location of tumor imaged post-operatively via CT and/or MRI.
OUTLINE: This study will enroll evaluable patients undergoing surgical resection of
malignant, grade IV gliomas in both of two groups: those with , newly diagnosed GBM and
those with recurrent GBM. Patient, in each group (primary vs recurrent GBM) will be
randomized to one of 2 levels of ALA dose (10 and20 mg/kg) to be given orally at 6 hours
prior to anticipated midpoint of surgery.
Patients who have consented to this protocol will be randomly assigned to one of two ALA
dose groups. Randomization will be stratified by whether the tumor is newly diagnosed (i.e.
de novo) or recurrent. The data center will prepare sealed, opaque envelopes with the
randomized assignment to ALA dose and administration time and notify the pharmacy of the
trial site so that so that the correct ALA dose can be prepared.
- Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours
before the midpoint of surgery.
- Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6
hours before the midpoint of surgery.
- Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours
before the midpoint of surgery.
- Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours
before the midpoint of surgery.
For both patients with new and recurrent disease, biopsies will be taken at up to six sites
identified by the surgeon: in the tumor center, tumor edge, area surrounding the tumor (if
safe), areas seen to fluoresce intraoperatively and an area with MR enhancement outside the
tumor region (if this can be accomplished safely). Prior to collecting these biopsies
readings will be taken at the biopsied location with the PpIX point probe by the surgeon.
For each of the 6 biopsies, they will be divided into 3 parts and distributed for further
analysis as follows: one portion will be sent to the pathologist for assessment of tumor
percentage, one portion will be evaluated by the Division of Biophysics at the University of
Toronto for PpIX concentration and the other for assessment of fluorescence.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Assess 2 doses of 5-ALA
This clinical trial has ALA dose at 2 levels (10 and 20 mg/kg) and ALA administration time at 1 time point (6h). During surgery, the intraoperative fluorescence observations and PpIX concentration measurements will be taken by the surgeon. The second part of each biopsy will have the PpIX concentration determined.
6 hours before midpoint of surgery
Yes
Andrew Sloan, MD
Principal Investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
United States: Federal Government
CASE1305
NCT00752323
August 2008
Name | Location |
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Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |