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

NCT ID: NCT01116661

Last Updated: 2019-05-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2019-02-28

Brief Summary

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

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.

Conditions

Glioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ALA for glioma (WHO G1-IV) subjects

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

Group Type: EXPERIMENTAL

5-Aminolevuline Acid (ALA)

Intervention Type: DRUG

Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery

Interventions

5-Aminolevuline Acid (ALA)

Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Patient age 18 to 72 years.

3. Karnofsky performance of 60% or greater

4. 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.

5. 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.

6. 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

1. Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA).

2. Subjects with a history or family history of Porphyrias

3. 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.

4. Pregnancy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Mitchel Berger

MD, Chairman

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchel S Berger, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF Department of Neurosurgery

Locations

UCSF Department of Neurosurgery

San Francisco, California, United States

Countries

United States

References

Widhalm G, Olson J, Weller J, Bravo J, Han SJ, Phillips J, Hervey-Jumper SL, Chang SM, Roberts DW, Berger MS. The value of visible 5-ALA fluorescence and quantitative protoporphyrin IX analysis for improved surgery of suspected low-grade gliomas. J Neurosurg. 2019 May 10;133(1):79-88. doi: 10.3171/2019.1.JNS182614. Print 2020 Jul 1.

Reference Type: DERIVED

PMID: 31075771 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

10101

Identifier Type: -

Identifier Source: org_study_id