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.
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 Type
OBSERVATIONAL
Enrollment
69
single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively
performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.
George Washington University
Washington D.C., District of Columbia, United States
Delray Medical Center
Delray Beach, Florida, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Saint Alphonsus Regional Medical Center
Boise, Idaho, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
CentraCare St. Cloud Hospital
Saint Cloud, Minnesota, United States
St. Luke's Marion Bloch Neuroscience Institute
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
...and 7 more locations
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.
Time frame: 6 weeks
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.
Time frame: 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.
Time frame: 6 weeks
Ki-67 proliferation index
Ki-67 is a prognostic marker for cancer
Time frame: 6 weeks
Karnofsky Performance Scale
Scale from 0-100, function from low to high, with 100 being normal
Time frame: 6 weeks
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