Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
Condition: Adrenocortical Carcinoma; Gastrointestinal Carcinoid Tumor; Kidney Cancer; Neuroblastoma; Retinoblastoma; Sarcoma
MeSH terms: Neuroblastoma; Rhabdomyosarcoma; Carcinoid Tumor; Retinoblastoma; Adrenocortical Carcinoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Seneca Valley virus-001 may be able to kill certain kinds of tumor cells without
      damaging normal cells. Adding low dose cyclophosphamide (in part B of study) may help to kill
      even more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of Seneca Valley
      virus-001 in treating young patients with relapsed or refractory neuroblastoma,
      rhabdomyosarcoma, or rare tumors with neuroendocrine features.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To estimate the maximum-tolerated dose and/or recommended phase II dose of Seneca Valley
           virus-001 (NTX-010) when administered as a single infusion to pediatric patients with
           relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with
           neuroendocrine features (Wilms tumor, retinoblastoma, adrenocortical carcinoma, or
           carcinoid tumors). (Part A [completed])

        -  To confirm that there is viral replication in these patients following NTX-010
           administration. (Part A [completed])

        -  To define and describe the toxicities of NTX-010 when administered on this schedule.
           (Part A [completed])

        -  To determine whether the number of regulatory T cells (as measured by flow cytometry)
           can effectively be reduced following administration of NTX-010 plus low-dose metronomic
           and intravenous cyclophosphamide. (Part B)

        -  To characterize the pharmacokinetics (time course of viral clearance) following NTX-010
           administration in these patients.

      Secondary

        -  To preliminarily define the antitumor activity of NTX-010 within the confines of a phase
           I study. (Part A [completed])

        -  To evaluate the development of neutralizing antibodies to NTX-010 following IV
           administration of NTX-010. (Part A [completed])

        -  To evaluate development of neutralizing antibodies to NTX-010 following the combination
           of NTX-010 and cyclophosphamide. (Part B)

        -  To investigate the presence and permissivity of occult circulating tumor cells prior to
           and after the initial intravenous administration of NTX-010.

      OUTLINE: This is a multicenter study.

      Part A (completed): Patients receive Seneca Valley virus-001 (NTX-010) IV over 1 hour on day
      1.

      Part B: Patients receive cyclophosphamide IV orally (PO) on days 1-14 and NTX-010 IV over 1
      hour on day 8. In the absence of disease progression or unacceptable toxicity, patients then
      receive cyclophosphamide orally (PO) on days 22-35, plus cyclophosphamide IV over 1 hour and
      NTX-010 IV over 1 hour on day 29.

      Tumor tissue samples are collected at baseline for biomarker studies. Blood and stool samples
      are collected periodically for neutralizing antibody and viral clearance studies. Additional
      blood samples may also be collected for the presence and permissivity of occult tumor cells.

      After completion of study treatment, patients are followed up periodically for up to 1 year.
    

Intervention name(s): Seneca Valley virus-001; cyclophosphamide; laboratory biomarker analysis; pharmacological study
Intervention type(s): Biological; Drug; Other; Other
Intervention MeSH terms: Cyclophosphamide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent neuroblastoma; previously treated childhood rhabdomyosarcoma; recurrent childhood rhabdomyosarcoma; recurrent Wilms tumor and other childhood kidney tumors; recurrent retinoblastoma; recurrent adrenocortical carcinoma; recurrent gastrointestinal carcinoid tumor