Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Conditions
Brief summary
The purpose of this study is to investigate the safety and performance of an investigational agent, known as 5-ALA or Gliolan (aminolevulinic acid), that many be useful to a surgeon for visualizing a tumor during surgery. It is also being studied to determine if there are differences in what Gliolan shows a surgeon compared to intraoperative magnetic resonance imaging (MRI)
Detailed description
PRIMARY OBJECTIVES: I. Determine the volume of residual enhancing tumor after a 5-ALA guided resection of a glioblastoma multiforme (GBM). II. Determine the volume of tissue removed compared to the measured enhancing tumor evaluated on a pre-operative MRI. SECONDARY OBJECTIVES: I. Evaluate the time to tumor progression. II. Evaluate the overall survival. OUTLINE: Patients receive aminolevulinic acid orally (PO) 2-4 hours before surgery. After completion of study treatment, patients are followed up for 2 weeks.
Interventions
DRUGaminolevulinic acid
Given PO
PROCEDUREtherapeutic conventional surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
Michael Vogelbaum, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a suspected or biopsy proven newly diagnosed GBM, or a recurrent GBM or suspected GBM (in patient with pathologically diagnosed prior World Health Organization \[WHO\] grade II or III tumor) in a patient undergoing a clinically-indicated surgery. * Age \>= 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Life expectancy is not a consideration for protocol entry * Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count \>= 1,500/uL * Platelets \>= 100,000/uL * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal * Creatinine within normal institutional limits; OR * Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal * 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; 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 or have a parent or guardian with the ability to understand and the willingness to sign a written informed consent
Exclusion criteria
* Prior therapy is not an exclusion criterion * Patients may not be receiving any other investigational agents * History of allergic reactions attributed to aminolevulinic acid (ALA) * Current treatment with hypericin (or an extract) or other photosensitizing agents * Personal or immediate family (parents, siblings, children) history of porphyrias * 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 * Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ALA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Volume of Residual Enhancing Tumor, as Determined by Intraoperative Volume MRI at a Single Time Point Without and With Gadolinium, Following Maximal Resection With Use of Aminolevulinic Acid | Day 1 | Volume of enhancing tumor (initial and residual) will be determined by use of a softwarebased volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study). |
| Comparison Between the Volume of Resected Tissue (Defined as the Volume of the Resection Cavity) and the Pre-operative Enhancing Tumor Volume | Up to day 1 | Volume of enhancing tumor (initial and residual) will be determined by use of a software-based volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study). |
Secondary
| Measure | Time frame |
|---|---|
| Time to Disease Progression (TTP), Determined by Review of MRIs Performed Post Operatively as Clinically Indicated, Evaluated With Use of the New International Criteria Proposed by the Response in NeuroOncology (RANO) Committee | From the date of surgery with aminolevulinic acid to the date of progression, assessed up to 1 year |
| Overall Survival, by Periodic Follow up Review of the Patient Charts and by Correlation With the Social Security Death Index | From the date of surgery with aminolevulinic acid to the date of death, assessed up to 4 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnostic (Aminolevulinic Acid) Patients receive aminolevulinic acid PO 2-4 hours before surgery.
aminolevulinic acid: Given PO
therapeutic conventional surgery: Undergo surgery | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Diagnostic (Aminolevulinic Acid) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Change in Volume of Residual Enhancing Tumor, as Determined by Intraoperative Volume MRI at a Single Time Point Without and With Gadolinium, Following Maximal Resection With Use of Aminolevulinic Acid
Volume of enhancing tumor (initial and residual) will be determined by use of a softwarebased volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study).
Time frame: Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnostic (Aminolevulinic Acid) | Change in Volume of Residual Enhancing Tumor, as Determined by Intraoperative Volume MRI at a Single Time Point Without and With Gadolinium, Following Maximal Resection With Use of Aminolevulinic Acid | -0.342 cc |
Primary
Comparison Between the Volume of Resected Tissue (Defined as the Volume of the Resection Cavity) and the Pre-operative Enhancing Tumor Volume
Volume of enhancing tumor (initial and residual) will be determined by use of a software-based volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study).
Time frame: Up to day 1
Population: Outcome never analyzed. Study closed with the IRB in 2014
Secondary
Overall Survival, by Periodic Follow up Review of the Patient Charts and by Correlation With the Social Security Death Index
Time frame: From the date of surgery with aminolevulinic acid to the date of death, assessed up to 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Diagnostic (Aminolevulinic Acid) | Overall Survival, by Periodic Follow up Review of the Patient Charts and by Correlation With the Social Security Death Index | 16 months |
Secondary
Time to Disease Progression (TTP), Determined by Review of MRIs Performed Post Operatively as Clinically Indicated, Evaluated With Use of the New International Criteria Proposed by the Response in NeuroOncology (RANO) Committee
Time frame: From the date of surgery with aminolevulinic acid to the date of progression, assessed up to 1 year
Population: Outcome never analyzed. Closed with the IRB in 2014