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

Primary Purpose

Glioma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

5-Aminolevuline Acid (ALA)

About this trial

This is an interventional treatment trial for Glioma focused on measuring glioma, high grade glioma, low grade glioma

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCSF Department of Neurosurgery

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALA for glioma (WHO G1-IV) subjects

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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. .

Full Information

NCT ID

NCT01116661

First Posted

May 3, 2010

Last Updated

May 7, 2019

Sponsor

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT01116661

Brief Title

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

Acronym

ALA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Terminated

Why Stopped

The primary objective for high grade gliomas has been met and the FDA has now approved the drug (Gleolan) for use in the United States.

Study Start Date

August 2010 (Actual)

Primary Completion Date

December 28, 2017 (Actual)

Study Completion Date

February 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Francisco

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma

Keywords

glioma, high grade glioma, low grade glioma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

199 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ALA for glioma (WHO G1-IV) subjects

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

5-Aminolevuline Acid (ALA)

Intervention Description

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

Primary Outcome Measure Information:

Title

The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content.

Description

Biopsies were examined by a pathologist to determine the amount of tumor content from the most fluorescent tissues

Time Frame

1 day

Secondary Outcome Measure Information:

Title

Number of Participants With Adverse Events

Description

Number of Participants with Adverse Events, as defined by grade 3 to 5 AEs and SAEs related to study drug. .

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

72 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mitchel S Berger, MD

Organizational Affiliation

UCSF Department of Neurosurgery

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF Department of Neurosurgery

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31075771

Citation

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 10:1-10. doi: 10.3171/2019.1.JNS182614. Online ahead of print.

Results Reference

derived

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

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