Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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.


Inclusion Criteria:



- 18 years or older

- Tumor Pathology: Newly diagnosed or recurrent malignant gliomas WHO grade IV

- Location: Supratentorial

- Resection: Tumor must be judged suitable for resection on the basis of imaging
studies.

- Consent: Patients must be able to give written, informed consent as approved by the
local IRB

- Newly Diagnosed Tumors: Patients with newly diagnosed Grade IV glioma who have had
not been previously treated with cranial radiation therapy

- Recurrent Tumors: Patients with recurrent Grade IV gliomas who have failed cranial
radiation therapy

Exclusion Criteria:

- Pregnant women or those who are breast feeding

- Individuals with history of cutaneous photosensitivity, porphyria, hypersensitivity
to porphyrins, photodermatosis, exfoliative dermatitis

- Individuals with history of liver disease in last 12 months

- Individuals with AST, ALT, ALP, or bilirubin >2.5x normal upper limit any time during
the previous 2 months

- Individuals with plasma creatinine>180 ╬╝mol/L

- Individuals who are unable to comply with photosensitivity precautions

- Individuals without a grade IV glioma

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Assess 2 doses of 5-ALA

Outcome Description:

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.

Outcome Time Frame:

6 hours before midpoint of surgery

Safety Issue:

Yes

Principal Investigator

Andrew Sloan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CASE1305

NCT ID:

NCT00752323

Start Date:

August 2008

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult giant cell glioblastoma
  • adult glioblastoma
  • adult gliosarcoma
  • recurrent adult brain tumor
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065