Trial Outcomes & Findings for A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors (NCT NCT01128218)
NCT ID: NCT01128218
Last Updated: 2023-11-30
Results Overview
Dose escalation from 10mg/kg to 50mg/kg to determine optimal 5-ALA dose
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
6 months
Results posted on
2023-11-30
Participant Flow
Participant milestones
| Measure |
Phase 1 Dose Level 1 (10mg/kg)
Dose Level 1: Participants were given a one-time, single-dose administration of oral10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 2 (20mg/kg)
Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 3 (30mg/kg)
Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 4 (40mg/kg)
Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 5 (50mg/kg)
Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 2 (40mg/kg)
Phase 2 (40mg/kg): Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
4
|
6
|
14
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
4
|
6
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors
Baseline characteristics by cohort
| Measure |
Phase 1 Dose Level 1 (10mg/kg)
n=3 Participants
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 2 (2omg/kg)
n=3 Participants
Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 3 (30mg/kg)
n=3 Participants
Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 4 (40mg/kg)
n=4 Participants
Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 5 (50mg/kg)
n=6 Participants
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 2 (40mg/kg)
n=14 Participants
Phase 2: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
19 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
14 Participants
n=115 Participants
|
|
Age, Continuous
|
64 years
n=5 Participants
|
61 years
n=7 Participants
|
63 years
n=5 Participants
|
71 years
n=4 Participants
|
52.5 years
n=21 Participants
|
56.36 years
n=10 Participants
|
58.63 years
n=115 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
16 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
17 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
14 Participants
n=10 Participants
|
32 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
14 Participants
n=10 Participants
|
32 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
4 participants
n=4 Participants
|
6 participants
n=21 Participants
|
14 participants
n=10 Participants
|
33 participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: There were no dose limiting toxicities observed at any dose level arm. Therefore, the 40mg/kg dose was arbitrarily chosen for the phase 2 portion of the study.
Dose escalation from 10mg/kg to 50mg/kg to determine optimal 5-ALA dose
Outcome measures
| Measure |
Phase 1 Dose Level 1 (10mg/kg)
n=3 Participants
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 2 (20mg/kg)
n=3 Participants
Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 3 (30mg/kg)
n=3 Participants
Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 4 (40mg/kg)
n=4 Participants
Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 5 (50mg/kg)
n=6 Participants
Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
|---|---|---|---|---|---|
|
Establish a Safe Dose for Oral 5-ALA Administration
|
0 Dose Limiting Toxicity
|
0 Dose Limiting Toxicity
|
0 Dose Limiting Toxicity
|
0 Dose Limiting Toxicity
|
0 Dose Limiting Toxicity
|
PRIMARY outcome
Timeframe: BaselinePopulation: Assessing sensitivity, specificity, positive predictive value, and negative predictive value in Phase 2 Study Population of N=14 Patients at 40 mg/kg Dose
The neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor and areas in the wall of the resection cavity that were judged to be normal, non-eloquent brain. A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist. We assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where True Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor These values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor. From these parameters we determined sensitivity, specificity and the positive and negative predictive values.
Outcome measures
| Measure |
Phase 1 Dose Level 1 (10mg/kg)
n=28 Biopsies
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 2 (20mg/kg)
Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 3 (30mg/kg)
Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 4 (40mg/kg)
Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 5 (50mg/kg)
Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
|---|---|---|---|---|---|
|
Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.
Sensitivity
|
63.64 Percentage
|
—
|
—
|
—
|
—
|
|
Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.
Specificity
|
100 Percentage
|
—
|
—
|
—
|
—
|
|
Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.
Positive Predictive Value
|
100 Percentage
|
—
|
—
|
—
|
—
|
|
Determine the Sensitivity, Specificity, and Positive Predictive Value of 5-ALA Mediated Fluorescence for Malignant Glioma Tissue in the Brain.
Negative Predictive Value
|
42.86 Percentage
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Phase 2 Study Population of N=14 Patients at 40 mg/kg Dose
Under blue light, the neurosurgeon will take two small biopsies per patient from areas identified as obvious tumor (fluorescent) and areas in the wall of the resection cavity that were judged to be normal (but possibly edematous), non-eloquent brain (non-fluorescent). A neuropathologist will review all biopsy specimens, including those taken from the solid tumor. Pathologic confirmation of tumor type will be made by the study reference neuropathologist. We assessed 5-ALA's resulting fluorescence for distinguishing tumor within the brain, where True Positive: Fluorescence showing Tumor and Biopsy result Tumor False Positive: Fluorescence showing Tumor and Biopsy result No Tumor True Negative: No Fluorescence and Biopsy result No Tumor False Negative: No Fluorescence and Biopsy result Tumor These values represent the characteristics of 5-ALA aka its ability to distinguish tumor from non-tumor.
Outcome measures
| Measure |
Phase 1 Dose Level 1 (10mg/kg)
n=28 Biopsies
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 2 (20mg/kg)
Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 3 (30mg/kg)
Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 4 (40mg/kg)
Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1 Dose Level 5 (50mg/kg)
Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
|---|---|---|---|---|---|
|
Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain
True Positives
|
14 Biopsies
|
—
|
—
|
—
|
—
|
|
Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain
True Negatives
|
6 Biopsies
|
—
|
—
|
—
|
—
|
|
Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain
False Positives
|
0 Biopsies
|
—
|
—
|
—
|
—
|
|
Assess 5-ALA's Resulting Fluorescence for Distinguishing Tumor Within the Brain
False Negatives
|
8 Biopsies
|
—
|
—
|
—
|
—
|
Adverse Events
Phase 1, Dose Level 1 (10mg/kg)
Serious events: 2 serious events
Other events: 0 other events
Deaths: 1 deaths
Phase 1, Dose Level 2 (20mg/kg)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 1, Dose Level 3 (30mg/kg)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 1, Dose Level 4 (40mg/kg)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 1, Dose Level 5 (50mg/kg)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 2 (40mg/kg)
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1, Dose Level 1 (10mg/kg)
n=3 participants at risk
Phase 1 Dose Level 1: Participants were given a one-time, single-dose administration of oral 10mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1, Dose Level 2 (20mg/kg)
n=3 participants at risk
Phase 1 Dose Level 2: Participants were given a one-time, single-dose administration of oral 20mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1, Dose Level 3 (30mg/kg)
n=3 participants at risk
Phase 1 Dose Level 3: Participants were given a one-time, single-dose administration of oral 30mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1, Dose Level 4 (40mg/kg)
n=4 participants at risk
Phase 1 Dose Level 4: Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 1, Dose Level 5 (50mg/kg)
n=6 participants at risk
Phase 1 Dose Level 5: Participants were given a one-time, single-dose administration of oral 50mg/kg Aminolevulinic Acid (5-ALA)
|
Phase 2 (40mg/kg)
n=14 participants at risk
Phase 2 Dose (40mg/kg): Participants were given a one-time, single-dose administration of oral 40mg/kg Aminolevulinic Acid (5-ALA)
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
death
|
33.3%
1/3 • Number of events 1 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/4 • 6 years
|
0.00%
0/6 • 6 years
|
0.00%
0/14 • 6 years
|
|
Infections and infestations
scalp wound abscess
|
33.3%
1/3 • Number of events 1 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/4 • 6 years
|
0.00%
0/6 • 6 years
|
0.00%
0/14 • 6 years
|
|
Surgical and medical procedures
severe cerebral edema
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/4 • 6 years
|
0.00%
0/6 • 6 years
|
7.1%
1/14 • Number of events 1 • 6 years
|
|
Nervous system disorders
partial seizure
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/3 • 6 years
|
0.00%
0/4 • 6 years
|
0.00%
0/6 • 6 years
|
7.1%
1/14 • Number of events 1 • 6 years
|
Other adverse events
Adverse event data not reported
Additional Information
Barbara Lokaitis, BA, CCRP / Senior Clinical Research Coordinator
SIU Medicine
Phone: 217.545.9737
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place