GliomaPhase 2ALANCT01116661
Safety Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain
A Phase 2 study testing 5-Aminolevuline Acid (ALA) in people with Glioma, run by University of California, San Francisco at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Glioma
- What is being tested?
- 5-Aminolevuline Acid (ALA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 199 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to 28 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Department of Neurosurgery
San Francisco, California, 94143
About this study
Official title: A Phase 2 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain
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.
Read the 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
- Being tested
- 5-Aminolevuline Acid (ALA)
- Keywords
- glioma, high grade glioma, low grade glioma
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-Aminolevuline Acid (ALA)Drug
Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery
| Study group | Role | What they receive |
|---|---|---|
| ALA for glioma (WHO G1-IV) subjects | Experimental | 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 Receives: Drug: 5-Aminolevuline Acid (ALA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 day
Secondary outcomes (1)
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. .
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2010 (estimated)
- Study startAug 2010
- Primary completion28 Dec 2017
- Study completion28 Feb 2019
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mitchel Berger, University of California, San Francisco
- Investigators
- Mitchel S Berger, MD, Principal investigator, UCSF Department of Neurosurgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116661
- Sponsor's protocol ID
- 10101
- Acronym
- ALA
- Status last verified
- May 2019
- First submitted
- 3 May 2010
- Last updated
- 29 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31075771
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Tumors of the Brain
- ClinicalTrials.gov ID
- NCT01116661
- Acronym / sponsor ID
- ALA / 10101
- Conditions
- Glioma
- Keywords
- glioma, high grade glioma, low grade glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 199 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Aug 2010 (actual)
- Primary completion
- 28 Dec 2017 (actual)
- Study completion
- 28 Feb 2019 (actual)
- First posted
- 5 May 2010 (estimated)
- Results
- Posted 29 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALA for glioma (WHO G1-IV) subjects | Experimental | Drug: 5-Aminolevuline Acid (ALA)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 |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-Aminolevuline Acid (ALA)Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery | Drug | ALA for glioma (WHO G1-IV) subjects |
Primary outcome
The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content.
Time frame: 1 day
Biopsies were examined by a pathologist to determine the amount of tumor content from the most fluorescent tissues
1 secondary outcome
Number of Participants With Adverse Events
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31075771Widhalm 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchel S Berger, MD principal investigator
UCSF Department of Neurosurgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-Aminolevuline Acid (ALA) in people with Glioma, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percentage of Biopsies Taken From the Most Fluorescent Tissues That Have Tumorous Content. (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01116661, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2019.