Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group Journal Article
| Authors: | Burke, M. J.; Ahern, C.; Weigel, B. J.; Poirier, J. T.; Rudin, C. M.; Chen, Y.; Cripe, T. P.; Bernhardt, M. B.; Blaney, S. M. |
| Article Title: | Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group |
| Abstract: | 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. © 2014 Wiley Periodicals, Inc. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; unclassified drug; fatigue; neutropenia; diarrhea; solid tumor; anorexia; neutrophil count; anemia; leukopenia; nausea; vomiting; cyclophosphamide; cancer pain; hypercalcemia; pediatric; abdominal pain; adrenal cortex carcinoma; alanine aminotransferase blood level; aspartate aminotransferase blood level; backache; chill; drug fever; hyperglycemia; lymphocytopenia; neuroendocrine tumor; alanine aminotransferase; aspartate aminotransferase; bilirubin; drug induced headache; hypoalbuminemia; hyponatremia; neuroblastoma; oncolytic virus; thrombocyte count; carcinoid; maximum tolerated dose; phase 1 clinical trial; rhabdomyosarcoma; rna virus; bilirubin blood level; virus particle; leukocyte; lymphocyte count; embryonal rhabdomyosarcoma; solid tumors; nephroblastoma; oncolytic; relapsed; human; male; female; priority journal; article; seneca valley virus; ntx 010; relapsed refractory solid tumor |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 62 |
| Issue: | 5 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2015-05-01 |
| Start Page: | 743 |
| End Page: | 750 |
| Language: | English |
| DOI: | 10.1002/pbc.25269 |
| PROVIDER: | scopus |
| PMCID: | PMC4376652 |
| PUBMED: | 25307519 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
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