title: A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting.
abstract: ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.
authors.affiliation: The NABTT CNS Consortium, Baltimore, MD 21231, USA.
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Abbed
authors.forename: Stephen
authors.initials: S
authors.lastname: Tatter
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Fred H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: Fred
authors.initials: F
authors.lastname: Barker
authors.forename: Jean
authors.initials: J
authors.lastname: Kracher
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
authors.forename: Joy D
authors.initials: JD
authors.lastname: Fisher
authors.forename: Kathryn
authors.initials: K
authors.lastname: Carson
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenblum
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: Jeff
authors.initials: J
authors.lastname: Olson
authors.forename: James
authors.initials: J
authors.lastname: Markert
authors.forename: Steven
authors.initials: S
authors.lastname: Rosenfeld
authors.forename: L Burt
authors.initials: LB
authors.lastname: Nabors
authors.forename: Steven
authors.initials: S
authors.lastname: Brem
authors.forename: Surasak
authors.initials: S
authors.lastname: Phuphanich
authors.forename: Scott
authors.initials: S
authors.lastname: Freeman
authors.forename: Rick
authors.initials: R
authors.lastname: Kaplan
authors.forename: James
authors.initials: J
authors.lastname: Zwiebel
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D014765:Viral Vaccines; D014779:Virus Replication / Q000235:genetics
chemical_list: D017501:Adenovirus E1B Proteins; D014765:Viral Vaccines; C464532:dl1520