This phase I trial studies the side effects and the best dose of viral therapy in treating young patients with solid tumors that have come back or that have not responded to standard therapy. Some tumors have cells with a genetic weakness that makes them unable to fight off a virus called wild-type reovirus. The virus causes cells with this weakness to die, and may therefore be able to kill tumor cells without damaging normal cells. Cyclophosphamide is a drug used in chemotherapy that stops tumor cells from dividing and causes them to die. Giving wild-type reovirus together with cyclophosphamide may kill more tumor cells.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REOLYSIN (wild-type reovirus) administered as an intravenous infusion daily for 5 days, every 28 days to children with relapsed or refractory solid tumors. II. To define and describe the toxicities of Reolysin in these patients. III. To define the toxicity and tolerability of combining Reolysin with oral cyclophosphamide in these patients. IV. To characterize the pharmacokinetics (time course of viral clearance) of Reolysin in children with refractory cancer. SECONDARY OBJECTIVES: I. To define the antitumor activity of Reolysin within the confines of a phase I study. II. To evaluate the development of neutralizing antibodies to Reolysin following intravenous administration of Reolysin alone and in combination with cyclophosphamide. III. To assess the biologic activity of Reolysin. OUTLINE: This is a dose-escalation study of wild-type reovirus. Patients receive wild-type reovirus intravenously (IV) over 60 minutes once daily (QD) on days 1-5. Some patients also receive cyclophosphamide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Given IV
Given PO
Correlative studies
Correlative studies
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Childrens Hospital of Orange County
Orange, California, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States
Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT), graded using the NCI CTCAE v. 4.0
Time frame: Up to 28 days
Time course of viral clearance of wild-type reovirus
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame: Up to 3 months
Development of neutralizing antibodies to wild-type reovirus
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Time frame: Up to 3 months
Disease response, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Will be reported descriptively.
Time frame: Up to 1 year
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Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
...and 17 more locations