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The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible patients of age 3\u201321 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1\u2010year progression\u2010free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1\u2010year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K\u2010ras mutations were identified in available samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26621","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T16:52:01Z","timestamp":1495731121000},"source":"Crossref","is-referenced-by-count":22,"title":["A pediatric trial of radiation\/cetuximab followed by irinotecan\/cetuximab in newly diagnosed diffuse pontine gliomas and high\u2010grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6446-9180","authenticated-orcid":false,"given":"Margaret E.","family":"Macy","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine\/Children's Hospital Colorado  Aurora 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