Malignant GliomasNCT02632370
5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor
An observational study of Malignant Gliomas, run by Constantinos Hadjipanayis at 17 sites in United States.
Trial summary
In support of the US marketing application for 5-ALA, this single arm trial is being conducted to establish the efficacy and safety of Gliolan® (5-ALA) in patients with newly diagnosed or recurrent malignant gliomas. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Malignant Gliomas
- What is being tested?
- Gliolan® and Fluorescence-Guided Surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 69 participants
- Where
- 17 sitesUnited States
- Study dates
- May 2016to 31 Dec 2018
- Phase
- Observational
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with new or recurrent malignant gliomas
Who may be able to join
- Subjects included must have an MRI documenting a primary brain tumor for which resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignant gliomas. Standard criteria for diagnosis will include a distinct ring-like pattern of contrast enhancement with thick irregular walls on MRI for patients with a presumed newly diagnosed malignant glioma.
- Age 18-80.
- Karnofsky>60%.
- Subjects must have normal organ and marrow function as defined below:
- Leukocytes >3,000/mL Platelets >100,000/mL Total bilirubin below upper limit of normal AST (SGOT)/ALT (SGPT) <2.5 X institutional upper limit of normal Creatinine below upper limit of normal OR Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- The effects of 5-aminolevulinic Acid (5-ALA) on the developing human fetus are unknown. For this reason, 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. A pregnancy test will be performed for all women of childbearing ability prior to surgery (see Exclusion Criteria below). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document. Translation will be provided as appropriate by institution.
- Inclusion of Women and Minorities: Both men and women and members of all ethnic groups are eligible for this trial.
Who cannot join
- Patients with radiographic tumors of, or involving, nonresectable midline, the basal ganglia, or brain stem as assessed by MRI.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Patients should refrain from use of other potential phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) for 72 h.
- Personal or family history of porphyria.
- 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. . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-aminolevulinic acid (5-ALA), breastfeeding should be discontinued if the mother is treated with 5-aminolevulinic acid (5-ALA).
- Women who are pregnant will be excluded from the trial as aminolevulinic acid (ALA) is unknown to be teratogenic or have abortifacient effects Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
University of New Mexico School of Medicine, Department of Neurosurgery
Albuquerque, New Mexico, 87131
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
St. Luke's University Health Network
Bethlehem, Pennsylvania, 18015
Saint Alphonsus Regional Medical Center
Boise, Idaho, 83706
Massachusetts General Hospital
Boston, Massachusetts, 02114
Delray Medical Center
Delray Beach, Florida, 33484
Henry Ford Hospital
Detroit, Michigan, 48202
Penn State- Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Kansas Medical Center
Kansas City, Kansas, 66160
St. Luke's Marion Bloch Neuroscience Institute
Kansas City, Missouri, 64111
Mount Sinai Beth Israel
New York, New York, 10003
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
CentraCare St. Cloud Hospital
Saint Cloud, Minnesota, 56303
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
George Washington University
Washington D.C., District of Columbia, 20037
About this study
Official title: A Multicenter Study of 5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor in Patients With Newly Diagnosed or Recurrent Malignant Gliomas: A Safety, Histopathology, and Correlative Biomarker Study
In support of the US marketing application for 5-ALA, this single arm trial is being conducted to establish the efficacy and safety of Gliolan® (5-ALA) in patients with newly diagnosed or recurrent malignant gliomas. The hypothesis of the study is Gliolan® (5-ALA), as an adjunct to tumor resection, is safe and that real-time tissue fluorescence correlates with malignant histopathology. The primary objective in this single arm study is to define the positive predictive value (PPV) of Gliolan®-induced PPIX fluorescence for malignant tumor at the time of initial resection and first use of FGS by taking a biopsy of tissue presenting with red fluorescence when observed during the course of resection of new or recurrent malignant gliomas. The functionality and performance reliability of the blue light excitation microscope platforms will be assessed.
Read the detailed description
Primary Objectives
- To determine whether Gliolan® (5-ALA)-induced PPIX fluorescence correlates with malignant tumor histopathology (in a minimum of 3-5 serial biopsies taken from the red fluorescent region of tissue resection).
- To determine the patient safety profile of both oral Gliolan® (5-ALA), as well as use of the fluorescence operative microscope. These will include use of commonly accepted toxicity measures as well as recording surgically-related neurological deficits within the six weeks after surgery.
- To determine functionality and performance reliability of the blue light excitation microscope platforms (Zeiss Pentero, Leica OH4, Leica OH6 and others).
Secondary Objectives
- To correlate PPIX-containing extracellular microvesicles recovered from blood (at multiple time points prior to and following tumor resection) with the pre-operative MRI tumor volume.
- To characterize the presence and longitudinal changes in microvesicle biomarkers recovered from blood evaluating EGFRvIII, IDH1/2 wt and mutations and others. These microvesicular blood genes will be identified and correlated with the same microvesicular genes identified in tissue at the time of surgery.
- Conditions
- Malignant Gliomas
- Being tested
- Gliolan®, Fluorescence-Guided Surgery
- Keywords
- Malignant Gliomas, 5-ALA, tumor resection, malignant tumor
- Medical subject headings
- Glioma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gliolan®Drug
Also called 5-ALA
single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively
Fluorescence-Guided SurgeryProcedure or surgery
Also called FGS
performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.
| Study group | Role | What they receive |
|---|---|---|
| Gliolan® | Gliolan® is presented as a powder for oral solution in 60 ml colorless glass vials. The formulation contains 1.5 g 5-aminolevulinic acid hydrochloride corresponding to 1.17 g of 5-aminolevulinic acid. The oral solution is intended for single (partial) use. Receives: Drug: Gliolan®; Procedure: Fluorescence-Guided Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of diagnostic tissue presence
Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.
Measured: 6 weeks
Secondary outcomes (4)
Presence of malignant glioma tumor cells
Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.
Measured: 6 weeks
WHO tumor type with grading
Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.
Measured: 6 weeks
Ki-67 proliferation index
Ki-67 is a prognostic marker for cancer
Measured: 6 weeks
Karnofsky Performance Scale
Scale from 0-100, function from low to high, with 100 being normal
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2015 (estimated)
- Study startMay 2016
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomasStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Constantinos Hadjipanayis
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor-investigator, Constantinos Hadjipanayis, Icahn School of Medicine at Mount Sinai
- Investigators
- Bob Carter, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632370
- Sponsor's protocol ID
- GCO 15-2034-0001
- Other IDs
- CGH932015, PRMC 15-085
- Status last verified
- Feb 2019
- First submitted
- 9 Dec 2015
- Last updated
- 25 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Study of 5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor in Patients With Newly Diagnosed or Recurrent Malignant Gliomas: A Safety, Histopathology, and Correlative Biomarker Study
- ClinicalTrials.gov ID
- NCT02632370
- Acronym / sponsor ID
- GCO 15-2034-0001
- Conditions
- Malignant Gliomas
- Keywords
- Malignant Gliomas, 5-ALA, tumor resection, malignant tumor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Constantinos HadjipanayisUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- May 2016
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 16 Dec 2015 (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.
In support of the US marketing application for 5-ALA, this single arm trial is being conducted to establish the efficacy and safety of Gliolan® (5-ALA) in patients with newly diagnosed or recurrent malignant gliomas. The hypothesis of the study is Gliolan® (5-ALA), as an adjunct to tumor resection, is safe and that real-time tissue fluorescence correlates with malignant histopathology. The primary objective in this single arm study is to define the positive predictive value (PPV) of Gliolan®-induced PPIX fluorescence for malignant tumor at the time of initial resection and first use of FGS by taking a biopsy of tissue presenting with red fluorescence when observed during the course of resection of new or recurrent malignant gliomas. The functionality and performance reliability of the blue light excitation microscope platforms will be assessed.
Detailed description
Primary Objectives
- To determine whether Gliolan® (5-ALA)-induced PPIX fluorescence correlates with malignant tumor histopathology (in a minimum of 3-5 serial biopsies taken from the red fluorescent region of tissue resection).
- To determine the patient safety profile of both oral Gliolan® (5-ALA), as well as use of the fluorescence operative microscope. These will include use of commonly accepted toxicity measures as well as recording surgically-related neurological deficits within the six weeks after surgery.
- To determine functionality and performance reliability of the blue light excitation microscope platforms (Zeiss Pentero, Leica OH4, Leica OH6 and others).
Secondary Objectives
- To correlate PPIX-containing extracellular microvesicles recovered from blood (at multiple time points prior to and following tumor resection) with the pre-operative MRI tumor volume.
- To characterize the presence and longitudinal changes in microvesicle biomarkers recovered from blood evaluating EGFRvIII, IDH1/2 wt and mutations and others. These microvesicular blood genes will be identified and correlated with the same microvesicular genes identified in tissue at the time of surgery.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gliolan® | – | Drug: Gliolan®, Procedure: Fluorescence-Guided SurgeryGliolan® is presented as a powder for oral solution in 60 ml colorless glass vials. The formulation contains 1.5 g 5-aminolevulinic acid hydrochloride corresponding to 1.17 g of 5-aminolevulinic acid. The oral solution is intended for single (partial) use. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with new or recurrent malignant gliomas
Key inclusion criteria (8 listed)
- Subjects included must have an MRI documenting a primary brain tumor for which resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignant gliomas. Standard criteria for diagnosis will include a distinct ring-like pattern of contrast enhancement with thick irregular walls on MRI for patients with a presumed newly diagnosed malignant glioma.
- Age 18-80.
- Karnofsky>60%.
- Subjects must have normal organ and marrow function as defined below:
- Leukocytes >3,000/mL Platelets >100,000/mL Total bilirubin below upper limit of normal AST (SGOT)/ALT (SGPT) <2.5 X institutional upper limit of normal Creatinine below upper limit of normal OR Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
Key exclusion criteria (5 listed)
- Patients with radiographic tumors of, or involving, nonresectable midline, the basal ganglia, or brain stem as assessed by MRI.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Patients should refrain from use of other potential phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) for 72 h.
- Personal or family history of porphyria.
- 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. . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-aminolevulinic acid (5-ALA), breastfeeding should be discontinued if the mother is treated with 5-aminolevulinic acid (5-ALA).
- Women who are pregnant will be excluded from the trial as aminolevulinic acid (ALA) is unknown to be teratogenic or have abortifacient effects Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.
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 |
|---|---|---|
| Gliolan®Also: 5-ALAsingle dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively | Drug | Gliolan® |
| Fluorescence-Guided SurgeryAlso: FGSperformed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken. | Procedure or surgery | Gliolan® |
Primary outcome
Incidence of diagnostic tissue presence
Time frame: 6 weeks
Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.
4 secondary outcomes
Presence of malignant glioma tumor cells
Time frame: 6 weeks
WHO tumor type with grading
Time frame: 6 weeks
Ki-67 proliferation index
Time frame: 6 weeks
Karnofsky Performance Scale
Time frame: 6 weeks
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 25 Feb 2019.
- Individual participant dataSharing planned: Undecided
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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.
Bob Carter, MD, PhD principal investigator
Massachusetts General Hospital
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Gliomas, run by Constantinos Hadjipanayis at 17 sites 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 8 inclusion and 5 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 25 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites 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.
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?
Incidence of diagnostic tissue presence (time frame: 6 weeks). 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 25 Feb 2019.