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

Phase 1

Completed

• Conditions: Retinoblastoma; Adrenocortical Carcinoma; Gastrointestinal Carcinoid Tumor; Kidney Cancer; Neuroblastoma; Sarcoma
• Interventions: Biological: Seneca Valley virus-001; Drug: cyclophosphamide; Other: laboratory biomarker analysis; Other: pharmacological study

• Registration Number: NCT01048892
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2010-01-13
• Study First Submitted QC: 2010-01-13
• Study First Posted: 2010-01-14
• Primary Completion: 2013-06
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-29
• Last Update Posted: 2014-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (NTX-010)	Seneca Valley virus-001	-
Treatment (NTX-010)	laboratory biomarker analysis	-
Treatment (NTX-010)	pharmacological study	-
Treatment (NTX-010)	cyclophosphamide	-

Primary Outcome Measures

Name	Time	Method
Safety and tolerability	12 months post-documented viral clearance
Recommended phase II dose of Seneca Valley virus-001 (NTX-010)	56 days

Secondary Outcome Measures

Name	Time	Method
Viral titers in blood and stool	Up to 56 days post treatment
Development of antibodies to NTX-010	Up to 4 weeks post treatment
Tumor response	Up to 12 months post documented viral clearance

Trial Locations

Locations (18)

UAB Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Children's Memorial Hospital - Chicago; 🇺🇸 Chicago, Illinois, United States

Riley's Children Cancer Center at Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

C.S. Mott Children's Hospital at University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Masonic Cancer Center at University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis; 🇺🇸 St. Louis, Missouri, United States

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