Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01502280 |
| Other study ID # |
IRB#10BN132 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
November 2010 |
| Est. completion date |
June 2018 |
Study information
| Verified date |
January 2017 |
| Source |
St. Joseph's Hospital and Medical Center, Phoenix |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Gliomas are the most common primary brain tumor, yet remain a challenge to effectively treat.
Mounting evidence suggests that survival improves with greater tumor removal, yet being able
do a complete removal can be difficult due to the tumor's infiltrating nature.
5-aminolevulinic acid (5-ALA) is a natural compound that, when patients take it by mouth 3
hours before surgery, is selectively taken up by glioma cells and causes a red/pink
fluorescence (glow) under a blue light that allows tumor margins to be seen during the course
of surgery. While this compound is used as a standard-of-care agent in Europe, it remains
under testing by the Food and Drug Administration (FDA). A recent clinical trial in Germany,
however, has demonstrated a significant improvement in the rate of complete resection for
certain brain tumors (65% vs. 34%).
The Barrow 5-ALA Intraoperative Confocal (BALANCE) Trial will measure the effect of 5-ALA on
the amount of glioma tumor removal. To improve the usefulness of 5-ALA, a new special
microscope fitted with a blue light, will be used to magnify microscopic fluorescence at the
tumor margins. The investigators' hypothesis is that 5-ALA fluorescence with the use of the
special microscope during surgery will greatly lower the amount of tumor left behind.
Description:
Gliomas are the most common primary brain tumor, yet are associated with a 12-14 month
overall survival in the United States. Mounting evidence suggests that survival improves with
greater extent of resection, yet achieving a complete radiographic resection is challenging
due to the tumor's infiltrating nature. Oral 5-aminolevulinic acid (5-ALA/Gliolan®) is a
natural compound that, when administered to patients within 3 hours prior to surgery, is
selectively metabolized by glioma cells and induces a red/pink fluorescence under blue light
that facilitates intraoperative identification of tumor margins. While this compound is used
as a standard-of-care agent in Europe, it remains under examination by the Food and Drug
Administration (FDA). A recent multicenter randomized, single-blind, controlled study in
Germany demonstrated a significant improvement in the rate of complete resection for
high-grade gliomas, as compared to conventional microneurosurgery (65% vs. 34%) (Stummer et
al., Lancet Oncology 2006).
Patients with presumed newly-diagnosed glioma will be entered into the trial. On the basis of
their expected extent of resection (low vs. high), they will be stratified in one of 2 groups
- Group 1 (expected high extent or resection) or Group 2 (expected low extent of resection).
Following stratification, patients with newly-diagnosed disease will be randomized to receive
either study drug (5-ALA/Gliolan®) or placebo (ascorbic acid) prior to surgery. Those who
have had previous biopsy only without further treatment will be eligible for randomization.
Intraoperatively, 5-ALA/Gliolan® patients will undergo resection with combined fluorescence
microscopy and confocal microscopy. Placebo patients will undergo resection with standard
light microscopy. Postoperatively, patients will have an MRI scan with and without contrast
within 48 hours of surgery. Subsequent analysis of each patient will include assessment of
the primary endpoint, that is,volume of residual disease (VRD) by volumetrically quantifying
the tumor before and after surgery using T1-weighted contrast-enhancement (high-grade
gliomas) or T2-weighted hyperintensity (low-grade gliomas). Similarly, volumetric extent of
resection will also be measured. Other secondary endpoints will include overall survival
(OS), progression-free survival (PFS), and National Institute of Health Stroke Scale (NIHSS)
(collected at baseline, 7-10 days post-op and at 6, 12, 18, and 24 months post op).
The Barrow 5-ALA Intraoperative Confocal (BALANCE) study will quantify the impact of
5-ALA/Gliolan(R) on low- and high-grade glioma extent of resection. To enhance the efficacy
of 5-ALA/Gliolan(R), particularly for low-grade gliomas that fluoresce less vigorously due to
their comparatively lower cellular metabolism, intraoperative confocal microscopy will be
used to amplify microscopic fluorescence at the tumor margins. The investigators' hypothesis
is that, for both low- and high-grade gliomas, 5-ALA/Gliolan(R) fluorescence in conjunction
with intraoperative confocal microscopy will significantly lower the VRD.
Goals:
1. To determine the impact of intraoperative fluorescence and confocal microscopy on the
volume of residual disease following resection of a newly-diagnosed glioma.
Sub-goals:
1. To assess the feasibility and utility of combining intraoperative fluorescence with
confocal microscopy.
2. To determine the impact of this combined approach in improving volumetric extent of
resection.
3. To determine the impact of this combined approach in improving overall survival and
6-month progression-free survival.
