PMID- 25307519
OWN - NLM
STAT- MEDLINE
DCOM- 20150707
LR  - 20211021
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Print)
IS  - 1545-5009 (Linking)
VI  - 62
IP  - 5
DP  - 2015 May
TI  - Phase I trial of Seneca Valley Virus (NTX-010) in children with 
      relapsed/refractory solid tumors: a report of the Children's Oncology Group.
PG  - 743-50
LID - 10.1002/pbc.25269 [doi]
AB  - BACKGROUND: To determine the MTD of Seneca Valley Virus (NTX-010) in children 
      with relapsed/refractory solid tumors. Patients (>/= 3-</= 21 years) with 
      neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were 
      eligible. PROCEDURE: Part A (single dose of NTX-010) enrolled 13 patients at 
      three dose levels (1 x 10(9) viral particles (vp)/kg [n = 6], 1 x 10(10) vp/kg [n 
      = 3], 1 x 10(11) vp/kg [n = 4]). Diagnoses included neuroblastoma (n = 9), 
      rhabdomyosarcoma (n = 2), carcinoid tumor (n = 1), and adrenocorticocarcinoma (n 
      = 1). Part B added cyclophosphamide (CTX) (oral CTX (25 mg/m(2) /day) days 1-14 
      and IV CTX (750 mg/m(2) ) days 8 and 29) to two doses of NTX-010 (1 x 10(11) 
      vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included 
      neuroblastoma (n = 3), rhabdomyosarcoma (n = 1), Wilms tumor (n = 3), and 
      adrenocorticocarcinoma (n = 2). RESULTS: Twelve patients on Part A were evaluable 
      for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional 
      grade >/= 3 related adverse events (AEs) included leukopenia (n = 1), neutropenia 
      (n = 3), lymphopenia (n = 3), and tumor pain (n = 1). No DLTs occurred on part B. 
      Other grade >/= 3 related AEs on Part B included: Leukopenia (n = 3), nausea (n = 
      1), emesis (n = 1), anemia (n = 1), neutropenia (n = 4), platelets (n = 1), 
      alanine aminotransferase (n = 1), and lymphopenia (n = 2). All patients cleared 
      NTX-010 from blood and stool by 3 weeks with 17/18 patients developing 
      neutralizing antibodies. CONCLUSION: NTX-010 is feasible and tolerable at the 
      dose levels tested in pediatric patients with relapsed/refractory solid tumors 
      either alone or in combination with cyclophosphamide. However, despite the 
      addition of cyclophosphamide, neutralizing antibodies appeared to limit 
      applicability.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Burke, Michael J
AU  - Burke MJ
AD  - Department of Pediatrics, Division of Hematology/Oncology/BMT, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Ahern, Charlotte
AU  - Ahern C
FAU - Weigel, Brenda J
AU  - Weigel BJ
FAU - Poirier, John T
AU  - Poirier JT
FAU - Rudin, Charles M
AU  - Rudin CM
FAU - Chen, Yingbei
AU  - Chen Y
FAU - Cripe, Timothy P
AU  - Cripe TP
FAU - Bernhardt, M Brooke
AU  - Bernhardt MB
FAU - Blaney, Susan M
AU  - Blaney SM
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - U01 CA097452/CA/NCI NIH HHS/United States
GR  - UM1 CA097452/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141012
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Neutralizing/blood
MH  - Antineoplastic Agents, Alkylating/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Combined Modality Therapy
MH  - Cyclophosphamide/*therapeutic use
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Neoplasm Recurrence, Local/pathology/*therapy/virology
MH  - Neoplasm Staging
MH  - Neoplasms/pathology/*therapy/virology
MH  - *Oncolytic Virotherapy
MH  - *Picornaviridae
MH  - Prognosis
MH  - *Salvage Therapy
MH  - Young Adult
PMC - PMC4376652
MID - NIHMS623880
OTO - NOTNLM
OT  - oncolytic
OT  - pediatric
OT  - relapsed
OT  - seneca valley virus
OT  - solid tumors
EDAT- 2014/10/14 06:00
MHDA- 2015/07/08 06:00
PMCR- 2016/05/01
CRDT- 2014/10/14 06:00
PHST- 2014/05/23 00:00 [received]
PHST- 2014/07/18 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/07/08 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1002/pbc.25269 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2015 May;62(5):743-50. doi: 10.1002/pbc.25269. Epub 2014 
      Oct 12.