Viral Therapy in Treating Young Patients With Relapsed or Refractory Solid Tumors
This phase I trial is studying the side effects and the best dose of viral therapy in treating young patients with relapsed or refractory solid tumors. A virus called wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving wild-type reovirus together with cyclophosphamide may kill more tumor cells.
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: wild-type reovirus
Other: pharmacogenomic studies
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors|
- Maximum-tolerated dose (MTD), defined as the maximum dose at which fewer than one-third of patients experience DLT, graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2010|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (virus and chemotherapy)
Patients receive wild-type reovirus IV over 60 minutes once daily on days 1-5. Some patients also receive oral cyclophosphamide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Biological: wild-type reovirus
Other Name: REOLYSINOther: pharmacogenomic studies
Other Name: Pharmacogenomic StudyDrug: cyclophosphamide
Other Names:Other: laboratory biomarker analysis
I. To estimate the maximum-tolerated dose (MTD) and/or recommended phase II dose of wild-type reovirus (Reolysin) in 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.
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 (Reolysin).
Patients receive Reolysin IV over 60 minutes once daily on days 1-5. Some patients also receive oral cyclophosphamide 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.