Pediatric Phase II Trials of Poly-ICLC in the Management of Newly Diagnosed and Recurrent Brain Tumors

• Type of Material: Article
• Authors: Lisa L. R. Hartman, University of California San Diego; John R. Crawford, University of California San Diego; Milan T. Makale, University of California San Diego; Mehrzad Milburn, University of California San Diego; Shweta Joshi, University of California San Diego; Andres M. Salazar, Childrens Hospital of Orange County; Beth Hasenauer, Childrens Hospital of Orange County; Scott R. VandenBerg, University of California San Diego; Tobey MacDonald, Emory University; Donald L. Durden, University of California San Diego
• Language: English
• Date: 2014-08-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Copyright © 2014 by Lippincott Williams & Wilkins.
• Final Published Version (URL): http://dx.doi.org/10.1097/MPH.0000000000000047
• Title of Journal or Parent Work: Journal of Pediatric Hematology/Oncology
• ISSN: 1077-4114
• Volume: 36
• Issue: 6
• Start Page: 451
• End Page: 457
• Grant/Funding Information: Partially supported by award numbers NIH RO1 CA75737 and T32 CA121938 from the National Cancer Institute as well as Moores UCSD Cancer Center Early Clinical Trials Award funded under the Cancer Center Support Grant 5 P30 CA23100-21.
• Keywords: LOW-GRADE GLIOMAS; POLYNUCLEOTIDES; ACID; Oncology; pediatric gliomas; ADULTS; PHOSPHORYLATION; CHILDRENS ONCOLOGY GROUP; IMMUNE-RESPONSES; CARBOXYMETHYL CELLULOSE; L-LYSINE; toll receptor; Hematology; CENTRAL-NERVOUS-SYSTEM; Pediatrics; Science & Technology; toxicity; phase I/II; poly-ICLC; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

Brain tumors are the most common solid tumor diagnosed in childhood that account for significant morbidity and mortality. New therapies are urgently needed; hence, we conducted the first ever prospective open-label phase II trials of the biological response modifier, poly-ICLC, in children with brain tumors. Poly-ICLC is a synthetic double-stranded RNA that has direct antiviral, antineoplastic, and immune adjuvant effects. A total of 47 children representing a variety of brain tumor histopathologic subtypes were treated with poly-ICLC. On the basis of the results of the initial phase II trial, an expanded prospective phase II trial in low-grade glioma (LGG) has been initiated. MRI was used to acquire volume-based measures of tumor response. No dose-limiting toxicities have been observed. In the initial study 3 of 12 subjects with progressive high-grade gliomas (HGGs) responded, and 2 of 4 children with progressive LGG experienced stable disease for 18 to 24 months. In the follow-up LGG phase II study, 2 of 5 LGG patients were stable over 18 months, with 1 stable for 6 months. Overall 5 of 10 LGG patients have responded. On the basis of low toxicity and the promising LGG response, poly-ICLC may be effective for childhood LGG, and the results justify biomarker studies for personalization of poly-ICLC as a single agent or adjuvant.