Safety Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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 |
Drug: 5-Aminolevuline Acid (ALA)
Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery
|
Outcome Measures
Primary Outcome Measures
- The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content. [1 day]
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 [14 days]
Number of Participants with Adverse Events, as defined by grade 3 to 5 AEs and SAEs related to study drug. .
Eligibility Criteria
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.
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Patient age 18 to 72 years.
-
Karnofsky performance of 60% or greater
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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.
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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.
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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
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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.
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Pregnancy.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UCSF Department of Neurosurgery | San Francisco | California | United States | 94143 |
Sponsors and Collaborators
- University of California, San Francisco
Investigators
- Principal Investigator: Mitchel S Berger, MD, UCSF Department of Neurosurgery
Study Documents (Full-Text)
More Information
Publications
None provided.- 10101
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Single Dose ALA for Newly Diagnosed and Recurrent HGG |
---|---|
Arm/Group Description | 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery for both newly diagnosed and recurrent High grade gliomas |
Period Title: Overall Study | |
STARTED | 199 |
COMPLETED | 197 |
NOT COMPLETED | 2 |
Baseline Characteristics
Arm/Group Title | 5 - Aminolevuline Acid in Patients With HGG |
---|---|
Arm/Group Description | 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery |
Overall Participants | 197 |
Age (Count of Participants) | |
<=18 years |
NA
NaN
|
Between 18 and 65 years |
160
81.2%
|
>=65 years |
37
18.8%
|
Sex: Female, Male (Count of Participants) | |
Female |
78
39.6%
|
Male |
119
60.4%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
9
4.6%
|
Native Hawaiian or Other Pacific Islander |
2
1%
|
Black or African American |
0
0%
|
White |
162
82.2%
|
More than one race |
0
0%
|
Unknown or Not Reported |
24
12.2%
|
Region of Enrollment (participants) [Number] | |
United States |
197
100%
|
Outcome Measures
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 |
Outcome Measure Data
Analysis Population Description |
---|
All patient who received 5-Aminolevuline Acid prior to surgical resection |
Arm/Group Title | 5- Aminolevuline Acid Given to HGG Participants |
---|---|
Arm/Group Description | 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery |
Measure Participants | 197 |
Median (95% Confidence Interval) [percentage of biopsies] |
90.9
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Patients who received study drug |
Arm/Group Title | 5- Aminolevuline Acid Given to HGG Participants |
---|---|
Arm/Group Description | 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery |
Measure Participants | 197 |
Count of Participants [Participants] |
14
7.1%
|
Adverse Events
Time Frame | From time of ALA dosing up to 14 days post- operative | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | 5- Aminolevuline Acid Given to HGG Participants | |
Arm/Group Description | 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery | |
All Cause Mortality |
||
5- Aminolevuline Acid Given to HGG Participants | ||
Affected / at Risk (%) | # Events | |
Total | 59/199 (29.6%) | |
Serious Adverse Events |
||
5- Aminolevuline Acid Given to HGG Participants | ||
Affected / at Risk (%) | # Events | |
Total | 12/199 (6%) | |
Cardiac disorders | ||
Hypotension | 1/199 (0.5%) | 1 |
Infections and infestations | ||
Infection - with Grade 3 or 4 nuetrophils | 1/199 (0.5%) | 2 |
Infection - other | 1/199 (0.5%) | 1 |
Metabolism and nutrition disorders | ||
Hyponatremia | 2/199 (1%) | 2 |
Nervous system disorders | ||
Intracranial hemorrhage | 1/199 (0.5%) | 1 |
Mental status | 1/199 (0.5%) | 1 |
Seizure | 4/199 (2%) | 4 |
Vascular disorders | ||
thrombosis/embolism | 1/199 (0.5%) | 1 |
Vascular - other | 1/199 (0.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||
5- Aminolevuline Acid Given to HGG Participants | ||
Affected / at Risk (%) | # Events | |
Total | 25/199 (12.6%) | |
Blood and lymphatic system disorders | ||
Lymphopenia | 3/199 (1.5%) | 4 |
Hemoglobin decrease | 1/199 (0.5%) | 1 |
Cardiac disorders | ||
Hypotension | 2/199 (1%) | 2 |
hypertension | 1/199 (0.5%) | 1 |
General disorders | ||
Fatigue | 1/199 (0.5%) | 1 |
Metabolism and nutrition disorders | ||
ALT,SGPT increase | 2/199 (1%) | 2 |
Alkaline Phosphatase | 1/199 (0.5%) | 1 |
AST,SGOT increase | 1/199 (0.5%) | 1 |
Hyperbilirubinemia | 1/199 (0.5%) | 1 |
metabolic/Laboratory - other | 3/199 (1.5%) | 3 |
Skin and subcutaneous tissue disorders | ||
Photosensitivity | 5/199 (2.5%) | 8 |
Dermatology/skin | 3/199 (1.5%) | 3 |
Dry Skin | 1/199 (0.5%) | 1 |
Flushing | 1/199 (0.5%) | 1 |
Pain - skin | 1/199 (0.5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Mitch Berger, MD; Director of Neurosurgery |
---|---|
Organization | University of California San Francisco |
Phone | 415-353-7500 |
Mtich.Berger@ucsf.edu |
- 10101