QOL-38. A pilot phase 1a clinical trial proposal to study the dose and safety of natural marine product Fucoidan to improve fatigue in the patients with newly diagnosed glioblastoma (GBM) on adjuvant Temozolomide (TMZ) therapy

Abstract INTRODUCTION Glioblastoma (GBM) is the most aggressive primary brain tumor. GBM patients not only face a short overall survival but also experience debilitating fatigue secondary to the tumor and its treatment. Forty-Eight percent of patients with newly diagnosed GBM report fatigue; 90% of the patients with GBM recurrence develop fatigue (Röttgering et al. Neuro-Onc Adv 2022). Standard chemoradiation therapy is associated with 33% moderate to severe fatigue as one of the adverse effects (AEs) (Stupp et al. NEJM 2005). Both treatment and tumor related fatigue can significantly affect every aspect of quality of life (QOL) from daily functioning to emotional well-being, leading to early treatment termination. Currently, there are no therapeutics to relieve fatigue. Marine natural product, fucoidan is a seaweed-derived sulfated polysaccharide. Randomized clinical trials for colon, head and neck, and lung cancer patients suggest that fucoidan can improve certain AEs, particularly fatigue associated with tumor treatment with a favorable safety profile. HYPOTHESIS Fucoidan has a safe maximum tolerated dose (MTD) in the treatment of fatigue of the patients with GBM on adjuvant temozolomide therapy. STUDY DESIGN 3 + 3 Design. MTD is dose level at which 0/3 or 1/6 patients experience dose limited toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 patients encountering DLT. MTD dose test will start from over-the-counter available supplement dose 850 mg a day (212.5 mg four times daily) up to 4.05 g a day, the dose used by other study group for colon cancer trial (Ikeguchi et al. Oncol Lett 2011). Once the MTD is determined, the patient will continue the dose for completion of total 6-month therapy. OUTCOME This pilot study will establish a MTD dose for the next phase 1b clinical trial to improve tumor and treatment related fatigue by incorporating nature products to GBM therapy.