A Multicenter Study to Assess the Feasibility of 5-Aminolevulinic Acid (5-ALA) in Pediatric Brain Tumor Patients

Overview

This clinical trial focuses on pediatric patients aged 2 up to 18 years of age with a new or recurrent pediatric brain tumor, suspected to be either a high-grade or low-grade glioma, and scheduled for surgical removal. 5-aminolevulinic acid (5-ALA) is FDA-approved for improving brain tumor visualization in adults during surgery through fluorescence, enabling more complete removal of the tumor. This study aims to evaluate the feasibility of administering 5-ALA to pediatric brain tumor patients and to assess the quality of tumor fluorescence during surgery in this patient population. For the clinical trial, the patient will orally ingest 5-ALA 6 to 12 hours before brain surgery. All study participants will be provided standard medical care for removal of the brain tumor. All children enrolled in the study will be closely monitored prior to, during, and after surgery to ensure there are no reactions to the study drug. 5-ALA can make the patient more sensitive to sunlight and direct indoor lighting, referred to as photosensitivity, and can cause a sunburn-type reaction. It is for this reason that patients will be kept in subdued light conditions for 48 hours following surgery. Study participation starts once the patient is enrolled in the study until 6-month post-surgery.

The aim of this study is to assess the feasibility of administering 5-ALA pre-operatively and to access if the resulting 5-ALA-induced tumor fluorescence is adequate for fluorescence-guided brain tumor resection in pediatric patients. In this single-arm, multicenter study, the guardians of the pediatric patient with a newly diagnosed or select recurrent brain tumors will provide consent for the administration of 5-ALA. In relevant cases, assent from the pediatric patients will also be obtained. A total of twenty pediatric brain tumor patients will be treated to evaluate the feasibility of using 5-ALA in this population. All enrolled patients will receive an oral solution of 5-ALA at a dose of 20mg/kg body weight 6-12 hours prior to surgery, followed by tumor resection using either the institutional standard of care or the surgeon's preferred technique. Resection of fluorescent and non-fluorescent areas will proceed at the surgeon's discretion and the surgeon will indicate the fluorescence of each section. The fluorescence will be characterized as 'none', 'weak,' 'moderate,' or 'strong'; and described as 'patchy' or 'uniform'. When positive fluorescence is present, fluorescence-guided surgery will be performed under white light visualization with the ability to select for the use of appropriate filters adapted to the surgical microscope to allow specific wavelength of blue light to excite the tumor tissue during the operative procedure. Tissue fluorescence will be recorded by intraoperative photography. Biopsies, routinely performed during surgical tumor resection, will be obtained. An additional three to six research tissue specimens will be collected per patient for histopathologic analysis. If fluorescence is present in the tumor, three fluorescent specimens will be obtained from the tumor-core, tumor-margin, and regions just distant to the tumor margins as well as three non-fluorescent tissue specimens will be obtained adjacent to the resection cavity. If no fluorescence is visualized, this will be documented, and only three samples of non-fluorescent tissue specimens will be obtained from the tumor-core, tumor-margin, and regions just distant to the tumor margins. Histopathologic analysis on all collected fluorescent and non-fluorescent tissue specimens will be performed by a neuropathologist who will not be informed of the fluorescence status of the tissue specimens. The neuropathologist will characterize the biopsies and the additional three to six research tissue specimens by WHO grade, tumor type, and the number of tumor cells present. If institutions perform routine genetic and molecular analysis on resected tissue, this data will also be collected. 5-ALA makes a person more sensitive to sunlight and direct indoor lighting, referred to as photosensitivity, and can cause a sunburn-type reaction. Skin photosensitization lasts from approximately 24 to 48 hours following 5-ALA administration. It is for this reason that patients will be kept in low light conditions for 48 hours following surgery. Patients will undergo standard of care clinical assessments, including physical exams, neurological assessments (Karnofsky Performance Scale and the Lansky Scale), and laboratory evaluations, at several time points: upon entry into the trial (before surgery), within 48 hours after surgery, 2-weeks post-surgery, 6-weeks post-surgery, 3-months post-surgery, and 6-months post-surgery. MRIs will be conducted as part of standard care before surgery, within 48 hours of surgery, and at 3-months post-surgery, and 6-months post-surgery. All patients enrolled on the study will be monitored according to the protocol for 6-months post-surgery.