ATIM-09. SUCCESSFUL EXPERIENCE WITH CLINICAL TRIALS FOR HIGH GRADE GLIOMA IN A COMMUNITY SETTING

Abstract Background Recurrent high-grade gliomas in adults remain a deadly cancer with median survival of less than 1 year. In the absence of effective agents, immunotherapy with checkpoint inhibitors has been adopted as a potentially beneficial next step for recurrences with hypermutated or mismatch repair-mutated phenotypes. The rationale for their use, however, is based on case reports and studies with other types of cancer. Methods We reviewed 4 cases of hypermutated or mismatch repair-mutated recurrent high-grade gliomas treated with checkpoint inhibitors. Results All cases had recurrent high-grade glioma that harbored either a hypermutated phenotype and/or a mismatch repair mutation. Treatment with checkpoint inhibitor therapy resulted in no significant response. Conclusions In our experience, hypermutated or mismatch repair-mutated high-grade gliomas in adults do not respond to checkpoint inhibitors alone. This lack of efficacy is in agreement with underwhelming results of clinical trials examining checkpoint inhibitors in high-grade gliomas. The case reports of responders have been in pediatric patients with glioma and are likely a different subtype altogether.

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600 POSTER Hematologic pharmacodynamics linked to the pharmacokinetics of berubicin (B), a blood–brain barrier penetrating anthracycline active against high grade glioma, in phase I/II clinical trials

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)72534-5 ◽

2008 ◽

Vol 6 (12) ◽

pp. 187-188 ◽

Cited By ~ 1

Author(s):

R. Kazerooni ◽

C. Conrad ◽

M.J. Johansen ◽

M. Sakamoto ◽

I. Fokt ◽

...

Keyword(s):

Clinical Trials ◽

Phase I ◽

Blood Brain Barrier ◽

High Grade Glioma ◽

Brain Barrier ◽

High Grade ◽

Blood Brain

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COVD-18. POTENTIAL TO HARNESS SARS-COV-2 NEUROTROPISM IN THE DELIVERY OF ONCOLYTIC VIROTHERAPY FOR THE TREATMENT OF HIGH-GRADE GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.101 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii24-ii25

Author(s):

Amanda Immidisetti ◽

Sean Munier ◽

Nitesh Patel

Keyword(s):

Clinical Trials ◽

High Grade Glioma ◽

Oncolytic Viruses ◽

Wild Type Virus ◽

High Grade ◽

Wild Type ◽

Olfactory Pathway ◽

Non Invasive ◽

Pathogenic Virus ◽

Tumor Cell Lysis

Abstract BACKGROUND High-grade gliomas (HGG) pose therapeutic challenges stemming from blood brain barrier, infiltrative growth, suppressed immune function, and tumor heterogeneity. Oncolytic viruses (OVs) are gaining traction for addressing these challenges. There is evidence that the SARS-CoV-2 glycoprotein spike binds the ACE-2 receptor in nasal epithelium and reaches the brainstem and thalamus via axonal transport through the olfactory pathway, making it an attractive candidate for OV therapy. Prior studies on chimerization of pathogenic virus-derived glycoprotein spikes with non-pathogenic strains exploit neurotropism of a wild-type virus while improving the safety profile of the resulting OV. We review, 1) the engineering of chimeric OVs used in the treatment of HGG; 2) potential for a novel chimeric virotherapy in which the SARS-CoV-2 glycoprotein spike can be used to deliver OV therapy intranasally; and 3) areas which warrant further investigation to develop this approach for clinical use. METHODS We performed an extensive review of chimeric OVs and specific modifications engineered to optimize safety and efficacy. Additionally, we assessed potential to use these principals to engineer the SARS-CoV-2 glycoprotein spike onto a non-pathogenic, replication competent virus to yield a novel chimeric for noninvasive, intranasal delivery. RESULTS Viruses with pathogenic properties in wild-type have been successfully used as components of OVs and have demonstrated potential in both preclinical and clinical trials. Outcomes show that despite wild-type virulence, notable toxicities were not observed in clinical trials, highlighting the potential of viral pseudotyping as a safe therapeutic approach. CONCLUSIONS The proposed method to utilize the SARS-CoV-2 glycoprotein in a novel chimeric poses advantages including 1) potential for non-invasive delivery, 2) therapy without need for maximal or uniform tumor coverage due to replication competence, 3) ability to reach infiltrative glioma cells, 4) potential to reach the brainstem, and 5) stimulation of host immunity through tumor cell lysis and antigen presentation

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FSMP-05. KETOGENIC DIETS FOR HIGH-GRADE GLIOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab024.069 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. i17-i17

Author(s):

Amanda Immidisetti ◽

Detlev Boison

Keyword(s):

Clinical Trials ◽

Patient Population ◽

Standard Of Care ◽

High Grade Glioma ◽

High Grade ◽

Ketogenic Diets ◽

Pubmed Search ◽

Compare Study ◽

Study Designs ◽

Energy Dependent

Abstract BACKGROUND Given therapeutic challenges posed by high-grade glioma (HGG), multiple concomitant therapies, including metabolic adjuncts to standard of care, are warranted. Tumor cells are almost exclusively energy-dependent on glucose. Preclinical data supports the use of ketogenic diets (KDs) in this population to deplete the tumor microenvironment of glucose, thereby exerting anti-tumor effects while the surrounding parenchymal tissue utilizes ketones. OBJECTIVE The aim of this study was to conduct an up-to-date systematic review of the clinical use of ketogenic diets (KD) in the setting of high-grade glioma treatment and compare study designs, outcomes, and challenges in the translation of these methods from bench to bedside. METHODS We conducted comprehensive searches of both the national clinical trials database (clinicaltrials.gov) and pubmed.gov. Trials were included in our review if they were conducted in a patient population with high-grade glioma (either early or refractory) and at least one study arm included the use of a KD. RESULTS The clinicaltrials.gov search yielded 12 studies of which 11 met inclusion criteria. Five of these trials reported results. The PubMed search yielded 2 additional studies. Seven clinical trials with reported results on a total of 69 patients were considered. CONCLUSIONS The use of KD has proven to be safe and tolerable in early trials, however, further studies are warranted to examine efficacy. Challenges to feasibility include low patient enrollment and compliance, as dietary changes were reported to negatively affect quality of life. Additionally, variability between animal and plant-based KDs, duration of KD regimen, carbohydrate: fat ratio, underlying genetic factors that affect the induction of ketosis, and use of steroid therapy in this patient population may all contribute to inconsistent clinical data when compared to preclinical studies. Future larger scale clinical trials and prospective studies are needed to clarify the role of KDs in the treatment of HGG.

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