Aminolevulinic Acid in Visualizing a Tumor During Surgery in Patients With Glioblastoma Multiforme

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and performance of an investigational agent, known as 5-ALA or Gliolan (aminolevulinic acid), that many be useful to a surgeon for visualizing a tumor during surgery. It is also being studied to determine if there are differences in what Gliolan shows a surgeon compared to intraoperative magnetic resonance imaging (MRI)

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the volume of residual enhancing tumor after a 5-ALA guided resection of a glioblastoma multiforme (GBM). II. Determine the volume of tissue removed compared to the measured enhancing tumor evaluated on a pre-operative MRI. SECONDARY OBJECTIVES: I. Evaluate the time to tumor progression. II. Evaluate the overall survival. OUTLINE: Patients receive aminolevulinic acid orally (PO) 2-4 hours before surgery. After completion of study treatment, patients are followed up for 2 weeks.

Official Title
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A Phase 2 Comparative Study of 5-Aminolevulinic Acid (5-ALA) and Intraoperative MRI (iMRI) to Enhance Completeness of Resection of Glioblastoma

Conditions
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Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

Intervention / Treatment
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* Drug: aminolevulinic acid
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a suspected or biopsy proven newly diagnosed GBM, or a recurrent GBM or suspected GBM (in patient with pathologically diagnosed prior World Health Organization [WHO] grade II or III tumor) in a patient undergoing a clinically-indicated surgery. Age >= 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) Life expectancy is not a consideration for protocol entry Patients must have normal organ and marrow function as defined below: Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal Creatinine within normal institutional limits; OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately 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 a written informed consent Exclusion Criteria: Prior therapy is not an exclusion criterion Patients may not be receiving any other investigational agents History of allergic reactions attributed to aminolevulinic acid (ALA) Current treatment with hypericin (or an extract) or other photosensitizing agents Personal or immediate family (parents, siblings, children) history of porphyrias 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 Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ALA

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (aminolevulinic acid)<br>Patients receive aminolevulinic acid PO 2-4 hours before surgery. | Drug: aminolevulinic acid<br>* Given PO<br>* Other names: ALA;Procedure: therapeutic conventional surgery<br>* Undergo surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Volume of Residual Enhancing Tumor, as Determined by Intraoperative Volume MRI at a Single Time Point Without and With Gadolinium, Following Maximal Resection With Use of Aminolevulinic Acid | Volume of enhancing tumor (initial and residual) will be determined by use of a softwarebased volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study). | Day 1 | 
| Comparison Between the Volume of Resected Tissue (Defined as the Volume of the Resection Cavity) and the Pre-operative Enhancing Tumor Volume | Volume of enhancing tumor (initial and residual) will be determined by use of a software-based volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study). | Up to day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression (TTP), Determined by Review of MRIs Performed Post Operatively as Clinically Indicated, Evaluated With Use of the New International Criteria Proposed by the Response in NeuroOncology (RANO) Committee |  | From the date of surgery with aminolevulinic acid to the date of progression, assessed up to 1 year | 
| Overall Survival, by Periodic Follow up Review of the Patient Charts and by Correlation With the Social Security Death Index |  | From the date of surgery with aminolevulinic acid to the date of death, assessed up to 4 years |