A Phase 1 Dose Escalation Study of Seneca Valley Virus (NTX-010), A Replication-Competent Picornavirus, in Relapsed/Refractory Pediatric Patients With Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
- To estimate the maximum-tolerated dose and/or recommended phase II dose of Seneca
Valley virus-001 (NTX-010) when administered as a single infusion to pediatric patients
with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with
neuroendocrine features (Wilms tumor, retinoblastoma, adrenocortical carcinoma, or
carcinoid tumors). (Part A [completed])
- To confirm that there is viral replication in these patients following NTX-010
administration. (Part A [completed])
- To define and describe the toxicities of NTX-010 when administered on this schedule.
(Part A [completed])
- To determine whether the number of regulatory T cells (as measured by flow cytometry)
can effectively be reduced following administration of NTX-010 plus low-dose metronomic
and intravenous cyclophosphamide. (Part B)
- To characterize the pharmacokinetics (time course of viral clearance) following NTX-010
administration in these patients.
- To preliminarily define the antitumor activity of NTX-010 within the confines of a
phase I study. (Part A [completed])
- To evaluate the development of neutralizing antibodies to NTX-010 following IV
administration of NTX-010. (Part A [completed])
- To evaluate development of neutralizing antibodies to NTX-010 following the combination
of NTX-010 and cyclophosphamide. (Part B)
- To investigate the presence and permissivity of occult circulating tumor cells prior to
and after the initial intravenous administration of NTX-010.
OUTLINE: This is a multicenter study.
Part A (completed): Patients receive Seneca Valley virus-001 (NTX-010) IV over 1 hour on day
Part B: Patients receive cyclophosphamide IV orally (PO) on days 1-14 and NTX-010 IV over 1
hour on day 8. In the absence of disease progression or unacceptable toxicity, patients then
receive cyclophosphamide orally (PO) on days 22-35, plus cyclophosphamide IV over 1 hour and
NTX-010 IV over 1 hour on day 29.
Tumor tissue samples are collected at baseline for biomarker studies. Blood and stool
samples are collected periodically for neutralizing antibody and viral clearance studies.
Additional blood samples may also be collected for the presence and permissivity of occult
After completion of study treatment, patients are followed up periodically for up to 1 year.
Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability
Michael J. Burke, MD
Masonic Cancer Center, University of Minnesota
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin||Milwaukee, Wisconsin 53226|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Baylor University Medical Center - Houston||Houston, Texas 77030-2399|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|C.S. Mott Children's Hospital at University of Michigan Medical Center||Ann Arbor, Michigan 48109-0286|
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|Riley's Children Cancer Center at Riley Hospital for Children||Indianapolis, Indiana 46202-5225|
|UAB Comprehensive Cancer Center||Birmingham, Alabama 35294|