TY - JOUR
T1 - Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors
T2 - A report of the Children's Oncology Group
AU - Burke, Michael J.
AU - Ahern, Charlotte
AU - Weigel, Brenda J.
AU - Poirier, John T.
AU - Rudin, Charles M.
AU - Chen, Yingbei
AU - Cripe, Timothy P.
AU - Bernhardt, M. Brooke
AU - Blaney, Susan M.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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 (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/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 (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/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. Pediatr Blood Cancer 2015;62:743-750.
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 (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/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 (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/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. Pediatr Blood Cancer 2015;62:743-750.
KW - Oncolytic
KW - Pediatric
KW - Relapsed
KW - Seneca valley virus
KW - Solid tumors
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U2 - 10.1002/pbc.25269
DO - 10.1002/pbc.25269
M3 - Article
C2 - 25307519
AN - SCOPUS:84925352074
SN - 1545-5009
VL - 62
SP - 743
EP - 750
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 5
ER -