Glioma
Conditions
Keywords
glioma, high grade glioma, low grade glioma
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.
Interventions
DRUG5-Aminolevuline Acid (ALA)
Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. . |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 - Aminolevuline Acid in Patients With HGG 5-Aminolevuline Acid: Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery | 197 |
| Total | 197 |
Baseline characteristics
| Characteristic | 5 - Aminolevuline Acid in Patients With HGG |
|---|---|
| Age, Categorical <=18 years | NA Participants |
| Age, Categorical >=65 years | 37 Participants |
| Age, Categorical Between 18 and 65 years | 160 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants |
| Race (NIH/OMB) White | 162 Participants |
| Region of Enrollment United States | 197 participants |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 59 / 199 |
| other Total, other adverse events | 25 / 199 |
| serious Total, serious adverse events | 12 / 199 |
Outcome results
Primary
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
Time frame: 1 day
Population: All patient who received 5-Aminolevuline Acid prior to surgical resection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5- Aminolevuline Acid Given to HGG Participants | The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content. | 90.9 percentage of biopsies |
Secondary
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. .
Time frame: 14 days
Population: Patients who received study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5- Aminolevuline Acid Given to HGG Participants | Number of Participants With Adverse Events | 14 Participants |