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.
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.
Chiocca
E Antonio
EA
The NABTT CNS Consortium, Baltimore, MD 21231, USA.
Abbed
Khalid M
KM
Tatter
Stephen
S
Louis
David N
DN
Hochberg
Fred H
FH
Barker
Fred
F
Kracher
Jean
J
Grossman
Stuart A
SA
Fisher
Joy D
JD
Carson
Kathryn
K
Rosenblum
Mark
M
Mikkelsen
Tom
T
Olson
Jeff
J
Markert
James
J
Rosenfeld
Steven
S
Nabors
L Burt
LB
Brem
Steven
S
Phuphanich
Surasak
S
Freeman
Scott
S
Kaplan
Rick
R
Zwiebel
James
J
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
D017501:Adenovirus E1B Proteins; D014765:Viral Vaccines; C464532:dl1520