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Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: a report of the Children's Oncology Group. Pediatr Blood Cancer 2015 May;62(5):743-50

Date

10/14/2014

Pubmed ID

25307519

Pubmed Central ID

PMC4376652

DOI

10.1002/pbc.25269

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 × 10(9) viral particles (vp)/kg [n = 6], 1 × 10(10) vp/kg [n = 3], 1 × 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 × 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.

Author List

Burke MJ, Ahern C, Weigel BJ, Poirier JT, Rudin CM, Chen Y, Cripe TP, Bernhardt MB, Blaney SM

Author

Michael James Burke MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Antibodies, Neutralizing
Antineoplastic Agents, Alkylating
Child
Child, Preschool
Combined Modality Therapy
Cyclophosphamide
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Humans
Male
Maximum Tolerated Dose
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasms
Oncolytic Virotherapy
Picornaviridae
Prognosis
Salvage Therapy
Young Adult
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a