Phase I Trial of Seneca Valley Virus (NTX-010) in Children With Relapsed/Refractory Solid Tumors: A Report of the Children's Oncology Group

BackgroundTo 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. ProcedurePart A (single dose of NTX-010) enrolled 13 patients at three dose levels (1x10(9) viral particles (vp)/kg [n=6], 1x10(10)vp/kg [n=3], 1x10(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 (25mg/m(2)/day) days 1-14 and IV CTX (750mg/m(2)) days 8 and 29) to two doses of NTX-010 (1x10(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). ResultsTwelve 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. ConclusionNTX-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. (c) 2014 Wiley Periodicals, Inc.