Malignant Gliomas
Conditions
Keywords
Malignant Gliomas, 5-ALA, tumor resection, malignant tumor
Brief 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. 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.
Interventions
DRUGGliolan®
single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively
PROCEDUREFluorescence-Guided Surgery
performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.
Sponsors
Massachusetts General Hospital
Constantinos Hadjipanayis
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of diagnostic tissue presence | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of malignant glioma tumor cells | 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. |
| WHO tumor type with grading | 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. |
| Ki-67 proliferation index | 6 weeks | Ki-67 is a prognostic marker for cancer |
| Karnofsky Performance Scale | 6 weeks | Scale from 0-100, function from low to high, with 100 being normal |
Countries
United States
Outcome results
None listed