Safety Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain

Study Overview
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Brief Summary
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The prodrug, 5-Aminolevulinic acid (ALA), has been shown to lead to intracellular accumulation of fluorescent porphyrins in high grade malignant gliomas in the brain. On imaging, this accumulation of fluorescent porphyrins helps delineate tumor borders, resulting in the surgeon being better able to visualize and thus able to make a complete, or near-complete resection of the tumor.

Detailed Description
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The drug, 5-aminolevulinic acid (ALA), which leads to intracellular accumulation of fluorescent porphyrins in gliomas will be used under investigation for identification and resection of high and low grade gliomas. Surgery will be done using a modified neurosurgical microscope, with a fluorescent kit that enables switching from the conventional white light to a violet-blue excitation light for visualization during tumor resection. If deemed safe by the neurosurgeon, any area of the resection bed determined to be fluorescence-positive for tumor will be removed with appropriate designation of tissue for histopathological evaluation. After this resection, additional fluorescence images will be obtained and the process repeated until the image is negative for tumor. At all times, the decision to resect will be limited by clinical judgment of safety. The desire is that a more complete resection will occur due to the surgeon's ability to better visualize and distinguish between tumor and normal tissue, and thus be able to remove as much, or most of, the tumorous tissue, resulting in a better outcome for the patient, or for future patients.

Official Title
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A Phase 2 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain

Conditions
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Glioma

Intervention / Treatment
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* Drug: 5-Aminolevuline Acid (ALA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presumptive diagnosis of high grade or low grade glioma based on imaging studies, or will have recurrent high-grade or low grade gliomas that have previously undergone diagnosis (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme). Both of these groups will be undergoing craniotomy for tumor resection. Patient age 18 to 72 years. Karnofsky performance of 60% or greater Patients must have normal organ and marrow function as defined below: Leukocytes >3,000/μL Absolute neutrophil count >1,500/μL Platelets >100,000/μL Total bilirubin within normal institutional limits AST (SGOT)/ALT (SGPT) <2.5 X institutional upper limit of normal Creatinine within normal institutional limits or Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. The effects of Aminolevulinic Acid (ALA) on the developing human fetus are unknown. Therefore, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Patient must have the ability to understand and the willingness to sign a written informed consent document or have a parent or guardian with the ability to understand and the willingness to sign the written informed consent. Exclusion Criteria: Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Subjects with a history or family history of Porphyrias Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALA for glioma (WHO G1-IV) subjects<br>Up to 300 patients with diagnosed glioma (WHO G1-IV) eligible for surgery will be entered into the trial and will be given 5-Aminolevulinic Acid (ALA) orally at a dose of 20mg/kg body weight preoperatively | Drug: 5-Aminolevuline Acid (ALA)<br>* Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content. | Biopsies were examined by a pathologist to determine the amount of tumor content from the most fluorescent tissues | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of Participants with Adverse Events, as defined by grade 3 to 5 AEs and SAEs related to study drug. . | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioma, high grade glioma, low grade glioma