Brain and Central Nervous System TumorsPhase 2NCT00752323
Imaging Procedure Using ALA in Finding Residual Tumor in Grade IV Malignant Astrocytoma
A Phase 2 study testing aminolevulinic acid and Surgical Resection in people with Brain and Central Nervous System Tumors, run by Andrew Sloan, MD at 1 site in United States.
Trial summary
RATIONALE: Imaging procedures that use aminolevulinic acid (ALA) may help find and diagnose residual tumor in participants with grade IV malignant astrocytoma who are undergoing surgery to remove the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- aminolevulinic acid and Surgical Resection
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Dec 2009to 14 Oct 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Tumor Pathology: Newly diagnosed or recurrent malignant gliomas WHO grade IV
- Location: Supratentorial
- Resection: Tumor must be judged suitable for resection on the basis of imaging studies.
- Consent: Participants must be able to give written, informed consent as approved by the local IRB
- Newly Diagnosed Tumors: Participants with newly diagnosed Grade IV glioma who have had not been previously treated with cranial radiation therapy
- Recurrent Tumors: Participants with recurrent Grade IV gliomas who have failed cranial radiation therapy
Who cannot join
- Pregnant women or those who are breast feeding
- Individuals with history of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
- Individuals with history of liver disease in last 12 months
- Individuals with AST, ALT, ALP, or bilirubin >2.5x normal upper limit any time during the previous 2 months
- Individuals with plasma creatinine>180 μmol/L
- Individuals who are unable to comply with photosensitivity precautions
- Individuals without a grade IV glioma
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
About this study
Official title: Fluorescence-Guided Detection of Malignant Gliomas: A Dose Ranging Study Using 5-Aminolevulinic Acid (ALA) Induced Protoporphyrin (PpIX) in a Multicenter Phase II Clinical Trial
RATIONALE: Imaging procedures that use aminolevulinic acid (ALA) may help find and diagnose residual tumor in participants with grade IV malignant astrocytoma who are undergoing surgery to remove the tumor.
PURPOSE: Our primary long-term goal is to improve the completeness of surgical resection of malignant brain tumor through image- guided fluorescence localization. We hypothesize that the use of qualitative fluorescence imaging and point PpIX concentration quantification will enable more complete tumor resection than normal direct (i.e., white light) visualization, and thereby improve participant survival.
Read the detailed description
OBJECTIVES:
Primary
- Assess 2 doses of 5-ALA, 10kg/mg and 20kg/mg, to determine the optimum ALA dose in terms of both sensitivity and specificity for residual tumor. We will compare residual tumor detection by both in vivo qualitative and quantitative fluorescence imaging using histology of the biopsied tissue as the gold standard.
Secondary
- Assess the correlation between the recorded in vivo qualitative assessment of fluorescence signal from the neurosurgeon with the post-surgical (i.e., ex vivo) absolute PpIX concentration detected both intraoperatively and in ex vivo tissue biopsies.
Tertiary
- To determine the association between the presence of fluorescence in the surgical cavity and the post-operative image enhancement on MRI. This includes the relationship between the amount and location of residual tumor detected by fluorescence, PpIX concentration, and intra-operative frameless stereotaxy following maximal resection versus the amount and location of tumor imaged post-operatively via CT and/or MRI.
OUTLINE: This study will enroll evaluable participants undergoing surgical resection of malignant, grade IV gliomas in both of two groups: those with , newly diagnosed GBM and those with recurrent GBM. Participants in each group (primary vs recurrent GBM) will be randomized to one of 2 levels of ALA dose (10 and20 mg/kg) to be given orally at 6 hours prior to anticipated midpoint of surgery.
Participants who have consented to this protocol will be randomly assigned to one of two ALA dose groups. Randomization will be stratified by whether the tumor is newly diagnosed (i.e. de novo) or recurrent. The data center will prepare sealed, opaque envelopes with the randomized assignment to ALA dose and administration time and notify the pharmacy of the trial site so that so that the correct ALA dose can be prepared.
- Arm I: Newly diagnosed GBM participants receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
- Arm II: Newly diagnosed GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
- Arm III: Recurrent GBM participants receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
- Arm IV: Recurrent GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
For both participants with new and recurrent disease, biopsies will be taken at up to six sites identified by the surgeon: in the tumor center, tumor edge, area surrounding the tumor (if safe), areas seen to fluoresce intraoperatively and an area with MR enhancement outside the tumor region (if this can be accomplished safely). Prior to collecting these biopsies readings will be taken at the biopsied location with the PpIX point probe by the surgeon. For each of the 6 biopsies, they will be divided into 3 parts and distributed for further analysis as follows: one portion will be sent to the pathologist for assessment of tumor percentage, one portion will be evaluated by the Division of Biophysics at the University of Toronto for PpIX concentration and the other for assessment of fluorescence.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- aminolevulinic acid, Surgical Resection
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aminolevulinic acidDrug
Also called δ-Aminolevulinic acid Hydrochloride, 5-Amino-4-oxopentanoic acid Hydrochloride, 5-Aminolaevulinic acid Hydrochloride
Given orally
Surgical ResectionProcedure or surgery
Surgical resection - 6 biopsies from 3 fluorescent regions
| Study group | Role | What they receive |
|---|---|---|
| Arm I: Newly diagnosed GBM 10mg/kg | Experimental | Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery. Receives: Drug: aminolevulinic acid; Procedure: Surgical Resection |
| Arm II: Newly diagnosed GBM 20mg/kg | Experimental | Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery. Receives: Drug: aminolevulinic acid; Procedure: Surgical Resection |
| Arm III: Recurrent GBM 10mg/kg | Experimental | Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery. Receives: Drug: aminolevulinic acid; Procedure: Surgical Resection |
| Arm IV: Recurrent GBM 20mg/kg | Experimental | Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery. Receives: Drug: aminolevulinic acid; Procedure: Surgical Resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess 2 doses of 5-ALA
This clinical trial has ALA dose at 2 levels (10 and 20 mg/kg) and ALA administration time at 1 time point (6h). During surgery, the intraoperative fluorescence observations and PpIX concentration measurements will be taken by the surgeon. The second part of each biopsy will have the PpIX concentration determined.
Measured: 6 hours before midpoint of surgery
Secondary outcomes (2)
Correlation between intensity of in vivo fluorescence and the pathologist's quantification of tumor in biopsy specimens (e.g., percentage of tumor present) as measured by PpIX concentration and intra-operative fluorescence intensity
readings will be taken at the biopsied location with the PpIX point probe by the surgeon.
Measured: Quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor.
Correlation between the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection and the post-operative image enhancement on CT scan and/or MRI
Measured: Tumor tissue samples are obtained at the same two timepoints (the midpoint of surgery and then after maximal resection of the tumor)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2008 (estimated)
- Study start8 Dec 2009
- Primary completion15 Sep 2018
- Study completion14 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew Sloan, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew Sloan, MD, Case Comprehensive Cancer Center
- Investigators
- Andrew Sloan, MD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00752323
- Sponsor's protocol ID
- CASE1305
- Status last verified
- Sep 2021
- First submitted
- 12 Sep 2008
- Last updated
- 17 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluorescence-Guided Detection of Malignant Gliomas: A Dose Ranging Study Using 5-Aminolevulinic Acid (ALA) Induced Protoporphyrin (PpIX) in a Multicenter Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT00752323
- Acronym / sponsor ID
- CASE1305
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Andrew Sloan, MDUniversity, hospital or other
- Study start
- 8 Dec 2009 (actual)
- Primary completion
- 15 Sep 2018 (actual)
- Study completion
- 14 Oct 2018 (actual)
- First posted
- 15 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Imaging procedures that use aminolevulinic acid (ALA) may help find and diagnose residual tumor in participants with grade IV malignant astrocytoma who are undergoing surgery to remove the tumor.
PURPOSE: Our primary long-term goal is to improve the completeness of surgical resection of malignant brain tumor through image- guided fluorescence localization. We hypothesize that the use of qualitative fluorescence imaging and point PpIX concentration quantification will enable more complete tumor resection than normal direct (i.e., white light) visualization, and thereby improve participant survival.
Detailed description
OBJECTIVES:
Primary
- Assess 2 doses of 5-ALA, 10kg/mg and 20kg/mg, to determine the optimum ALA dose in terms of both sensitivity and specificity for residual tumor. We will compare residual tumor detection by both in vivo qualitative and quantitative fluorescence imaging using histology of the biopsied tissue as the gold standard.
Secondary
- Assess the correlation between the recorded in vivo qualitative assessment of fluorescence signal from the neurosurgeon with the post-surgical (i.e., ex vivo) absolute PpIX concentration detected both intraoperatively and in ex vivo tissue biopsies.
Tertiary
- To determine the association between the presence of fluorescence in the surgical cavity and the post-operative image enhancement on MRI. This includes the relationship between the amount and location of residual tumor detected by fluorescence, PpIX concentration, and intra-operative frameless stereotaxy following maximal resection versus the amount and location of tumor imaged post-operatively via CT and/or MRI.
OUTLINE: This study will enroll evaluable participants undergoing surgical resection of malignant, grade IV gliomas in both of two groups: those with , newly diagnosed GBM and those with recurrent GBM. Participants in each group (primary vs recurrent GBM) will be randomized to one of 2 levels of ALA dose (10 and20 mg/kg) to be given orally at 6 hours prior to anticipated midpoint of surgery.
Participants who have consented to this protocol will be randomly assigned to one of two ALA dose groups. Randomization will be stratified by whether the tumor is newly diagnosed (i.e. de novo) or recurrent. The data center will prepare sealed, opaque envelopes with the randomized assignment to ALA dose and administration time and notify the pharmacy of the trial site so that so that the correct ALA dose can be prepared.
- Arm I: Newly diagnosed GBM participants receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
- Arm II: Newly diagnosed GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
- Arm III: Recurrent GBM participants receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
- Arm IV: Recurrent GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
For both participants with new and recurrent disease, biopsies will be taken at up to six sites identified by the surgeon: in the tumor center, tumor edge, area surrounding the tumor (if safe), areas seen to fluoresce intraoperatively and an area with MR enhancement outside the tumor region (if this can be accomplished safely). Prior to collecting these biopsies readings will be taken at the biopsied location with the PpIX point probe by the surgeon. For each of the 6 biopsies, they will be divided into 3 parts and distributed for further analysis as follows: one portion will be sent to the pathologist for assessment of tumor percentage, one portion will be evaluated by the Division of Biophysics at the University of Toronto for PpIX concentration and the other for assessment of fluorescence.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I: Newly diagnosed GBM 10mg/kg | Experimental | Drug: aminolevulinic acid, Procedure: Surgical ResectionArm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery. |
| Arm II: Newly diagnosed GBM 20mg/kg | Experimental | Drug: aminolevulinic acid, Procedure: Surgical ResectionArm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery. |
| Arm III: Recurrent GBM 10mg/kg | Experimental | Drug: aminolevulinic acid, Procedure: Surgical ResectionArm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery. |
| Arm IV: Recurrent GBM 20mg/kg | Experimental | Drug: aminolevulinic acid, Procedure: Surgical ResectionArm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Tumor Pathology: Newly diagnosed or recurrent malignant gliomas WHO grade IV
- Location: Supratentorial
- Resection: Tumor must be judged suitable for resection on the basis of imaging studies.
- Consent: Participants must be able to give written, informed consent as approved by the local IRB
- Newly Diagnosed Tumors: Participants with newly diagnosed Grade IV glioma who have had not been previously treated with cranial radiation therapy
Key exclusion criteria (7 listed)
- Pregnant women or those who are breast feeding
- Individuals with history of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
- Individuals with history of liver disease in last 12 months
- Individuals with AST, ALT, ALP, or bilirubin >2.5x normal upper limit any time during the previous 2 months
- Individuals with plasma creatinine>180 μmol/L
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 |
|---|---|---|
| aminolevulinic acidAlso: δ-Aminolevulinic acid Hydrochloride, 5-Amino-4-oxopentanoic acid Hydrochloride, 5-Aminolaevulinic acid HydrochlorideGiven orally | Drug | Arm I: Newly diagnosed GBM 10mg/kg, Arm II: Newly diagnosed GBM 20mg/kg, Arm III: Recurrent GBM 10mg/kg, Arm IV: Recurrent GBM 20mg/kg |
| Surgical ResectionSurgical resection - 6 biopsies from 3 fluorescent regions | Procedure or surgery | Arm I: Newly diagnosed GBM 10mg/kg, Arm II: Newly diagnosed GBM 20mg/kg, Arm III: Recurrent GBM 10mg/kg, Arm IV: Recurrent GBM 20mg/kg |
Primary outcome
Assess 2 doses of 5-ALA
Time frame: 6 hours before midpoint of surgery
This clinical trial has ALA dose at 2 levels (10 and 20 mg/kg) and ALA administration time at 1 time point (6h). During surgery, the intraoperative fluorescence observations and PpIX concentration measurements will be taken by the surgeon. The second part of each biopsy will have the PpIX concentration determined.
2 secondary outcomes
Correlation between intensity of in vivo fluorescence and the pathologist's quantification of tumor in biopsy specimens (e.g., percentage of tumor present) as measured by PpIX concentration and intra-operative fluorescence intensity
Time frame: Quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor.
Correlation between the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection and the post-operative image enhancement on CT scan and/or MRI
Time frame: Tumor tissue samples are obtained at the same two timepoints (the midpoint of surgery and then after maximal resection of the tumor)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2021.
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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.
Andrew Sloan, MD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
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 aminolevulinic acid and Surgical Resection in people with Brain and Central Nervous System Tumors, run by Andrew Sloan, MD 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 6 inclusion and 7 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: finished, as of the sponsor's last update on 17 Sep 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Assess 2 doses of 5-ALA (time frame: 6 hours before midpoint of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Sep 2021.