A phase I trial and viral clearance study of reovirus (Reolysin) in children with relapsed or refractory extra‐cranial solid tumors: A Children's Oncology Group Phase I Consortium report
Author(s) -
Kolb E . Anders,
Sampson Valerie,
Stabley Deborah,
Walter Alexa,
SolChurch Katia,
Cripe Timothy,
Hingorani Pooja,
Ahern Charlotte Hsieh,
Weigel Brenda J.,
Zwiebel James,
Blaney Susan M.
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25464
Subject(s) - medicine , refractory (planetary science) , oncology , oncolytic virus , clinical trial , phases of clinical research , pediatric oncology , pediatrics , cancer , astrobiology , physics
Background Reovirus is a naturally occurring human virus that is cytopathic to malignant cells possessing an activated Ras signaling pathway. We conducted a phase I trial of Reolysin, a manufactured, proprietary isolate of purified reovirus, in children with relapsed/refractory extracranial solid tumors to define the recommended phase 2 dose (RP2D), toxicities, and pharmacokinetic properties when administered as a single agent or in combination with cyclophosphamide. Procedures Reolysin was administered intravenously for 5 consecutive days, every 28 days. Using a 3 + 3 design, the following dose levels were evaluated: 3 × 10 8 Tissue Culture Inhibitory Dose 50% (TCID 50 )/kg; 5 × 10 8 TCID 50 /kg (maximum dose was 3 × 10 10 TCID 50 ); and 5 × 10 8 TCID 50 /kg plus oral cyclophosphamide (50 mg/m 2 /day × 21 days). Results Twenty‐nine patients were enrolled; 28 were eligible and 24 were evaluable for toxicity and response. There were no hematologic dose‐limiting toxicities. Grade 5 respiratory failure and a Grade 5 thromboembolic event were reported, both in the setting of progressive disease. The median time to clear the reovirus viremia was 6.5 days. Eight of 24 patients were viremic beyond the 5 days of therapy, all were negative by day 17. No patient had detectable viral RNA in saliva or stool. There were no objective responses. Conclusions Reolysin at a dose of 5 × 10 8 TCID 50 /kg daily for 5 days was well tolerated in children alone and in combination with oral cyclophosphamide. Virus was cleared rapidly from the serum and shedding in stool and saliva was not detectable. Pediatr Blood Cancer 2015;62:751–758. © 2015 Wiley Periodicals, Inc.