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Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01048892
Recruitment Status : Completed
First Posted : January 14, 2010
Last Update Posted : January 30, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief 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.

Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Gastrointestinal Carcinoid Tumor Kidney Cancer Neuroblastoma Retinoblastoma Sarcoma Biological: Seneca Valley virus-001 Drug: cyclophosphamide Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of Seneca Valley Virus (NTX-010), A Replication-Competent Picornavirus, in Relapsed/Refractory Pediatric Patients With Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features
Study Start Date : September 2009
Actual Primary Completion Date : June 2013

Arm Intervention/treatment
Experimental: Treatment (NTX-010) Biological: Seneca Valley virus-001
Drug: cyclophosphamide
Other: laboratory biomarker analysis
Other: pharmacological study

Primary Outcome Measures :
  1. Safety and tolerability [ Time Frame: 12 months post-documented viral clearance ]
  2. Recommended phase II dose of Seneca Valley virus-001 (NTX-010) [ Time Frame: 56 days ]

Secondary Outcome Measures :
  1. Tumor response [ Time Frame: Up to 12 months post documented viral clearance ]
  2. Viral titers in blood and stool [ Time Frame: Up to 56 days post treatment ]
  3. Development of antibodies to NTX-010 [ Time Frame: Up to 4 weeks post treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed diagnosis of 1 of the following:

    • Neuroblastoma
    • Rhabdomyosarcoma
    • Wilms tumor
    • Retinoblastoma
    • Adrenocortical carcinoma
    • Carcinoid tumor
  • Relapsed or refractory disease
  • Measurable or evaluable disease
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • No known pulmonary tumors or metastases > 5 cm, as evaluated by chest CT scan
  • No clinically significant pulmonary and/or pericardial effusions (≥ grade 3), as evaluated by ECHO
  • No primary CNS tumors or known metastatic CNS disease involvement


  • Karnofsky performance status (PS) 50-100% (for patients > 16 years of age)
  • Lansky PS 50-100% (for patients ≤ 16 years of age)
  • Peripheral ANC ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 (transfusion independent, defined as no platelet transfusions within a 7-day period before study enrollment)
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:

    • ≤ 0.8 mg/dL (for patients 3 to 5 years of age)
    • ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
    • ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
    • ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
    • ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
    • ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
  • Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal (ULN)
  • SGPT ≤ 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin ≥ 2 g/dL
  • Oxygen saturation > 92% on room air
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to comply with the safety monitoring requirements of the study, in the opinion of the investigator
  • Completely toilet trained
  • No chronic diarrhea or urinary incontinence during the day or night, , and no in-dwellling urinary catheters
  • No uncontrolled infection
  • No known pregnant member of the household


  • Fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
  • At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
  • At least 3 months since prior stem cell transplantation or rescue (without TBI)

    • No evidence of active graft-vs-host disease
  • At least 6 weeks since other prior substantial bone marrow radiotherapy or treatment with therapeutic doses of MIBG
  • More than 3 weeks since prior myelosuppressive chemotherapy
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • More than 7 days since prior growth factor(s) that support platelet or white blood cell number or function
  • At least 7 days since prior biologic agents
  • At least 3 half-lives since prior monoclonal antibodies
  • More than 7 days since prior viral immunizations, including influenza
  • At least 42 days since the completion of any type of immunotherapy, e.g., tumor vaccines
  • No other viral immunizations after enrolling on study until 28 days after their last planned Seneca Valley virus-001 infusion or until documented viral clearance, whichever is longest
  • Concurrent corticosteroids allowed provided the patient has been on a stable or decreasing dose for the past 7 days
  • No other concurrent investigational drugs
  • No other concurrent anticancer agents (e.g., chemotherapy, radiotherapy, immunotherapy, or biologic therapy)
  • Prior treatment with Seneca Valley virus-001 is not allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01048892

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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Michael J. Burke, MD Masonic Cancer Center, University of Minnesota
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Responsible Party: Children's Oncology Group Identifier: NCT01048892    
Other Study ID Numbers: ADVL0911
CDR0000663520 ( Other Identifier: Clinical )
First Posted: January 14, 2010    Key Record Dates
Last Update Posted: January 30, 2014
Last Verified: January 2014
Keywords provided by Children's Oncology Group:
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
Additional relevant MeSH terms:
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Carcinoid Tumor
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms by Site
Neoplasms, Muscle Tissue
Neuroendocrine Tumors
Retinal Neoplasms
Eye Neoplasms
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms