Viral Therapy in Treating Young Patients With Relapsed or Refractory Solid Tumors
A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors
4 other identifiers
interventional
26
2 countries
27
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 11, 2010
CompletedFirst Posted
Study publicly available on registry
November 15, 2010
CompletedStudy Start
First participant enrolled
December 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedMay 13, 2014
January 1, 2014
3.3 years
November 11, 2010
May 9, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
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
Up to 28 days
Secondary Outcomes (3)
Time course of viral clearance of wild-type reovirus
Up to 3 months
Development of neutralizing antibodies to wild-type reovirus
Up to 3 months
Disease response, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 1 year
Study Arms (1)
Treatment (virus and chemotherapy)
EXPERIMENTALPatients receive wild-type reovirus IV over 60 minutes QD on days 1-5. Some patients also receive cyclophosphamide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients with relapsed or refractory solid tumors, with the exception of central nervous system (CNS) tumors and lymphomas, are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky \>= 50 for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and immunizations
- Must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
- At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
- At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- \>= 2 weeks for local palliative radiation therapy (XRT) (small port); \>= 24 weeks must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; \>= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
- No evidence of active graft vs host disease and \>= 12 weeks must have elapsed since stem cell transplant or infusion
- Patients must not have received any previous viral-based anti-neoplastic therapies
- Viral immunizations, including influenza, may not have been administered within 7 days prior to enrollment; Note: patients may not receive any viral immunizations after enrolling on study until 28 days post their last planned REOLYSIN infusion
- Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
- +16 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients who have an uncontrolled infection are not eligible
- Patients with chronic diarrhea, urinary incontinence during the day or at night, or patients who are not completely toilet trained will not be eligible
- Patients will be excluded if they have household contacts who are pregnant, immunosuppressed or infants less than 3 months of age; household contacts are defined as anyone living with the patient during the isolation period of the treatment cycles
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with known human immunodeficiency virus (HIV) or hepatitis B or C are excluded due to risk of viral infectivity of REOLYSIN; therefore, patients with a pre-existent infection are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
- Patients must not have received corticosteroids, immune modulators or antiviral therapy for 7 days prior to enrollment and must not have an anticipated need for any of these therapies, intravenous immune globulin (IVIG) must not have been administered within 2 weeks prior to enrollment
- Patients should avoid taking acetaminophen with REOLYSIN; whenever suitable, physicians should utilize alternative medications
- Patients with known germline mutations affecting Ras activation (e.g. NF-1, Cardio-facial-cutaneous syndrome, Noonan syndrome, Costello syndrome) will be excluded from enrollment
- Patients with known metastatic CNS disease involvement are excluded
- Patients with primary CNS tumors are excluded
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Childrens Hospital of Orange County
Orange, California, 92868-3874, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207-8426, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455, United States
Columbia University Medical Center
New York, New York, 10032, United States
Montefiore Medical Center
The Bronx, New York, 10467-2490, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
E. Anders Kolb
COG Phase I Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2010
First Posted
November 15, 2010
Study Start
December 1, 2010
Primary Completion
April 1, 2014
Last Updated
May 13, 2014
Record last verified: 2014-01