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

NCT ID: NCT01048892

Last Updated: 2014-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Brief Summary

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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

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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.

Conditions

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Adrenocortical Carcinoma Gastrointestinal Carcinoid Tumor Kidney Cancer Neuroblastoma Retinoblastoma Sarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (NTX-010)

Group Type EXPERIMENTAL

Seneca Valley virus-001

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

pharmacological study

Intervention Type OTHER

Interventions

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Seneca Valley virus-001

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

laboratory biomarker analysis

Intervention Type OTHER

pharmacological study

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

* 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

PRIOR CONCURRENT THERAPY:

* 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
Minimum Eligible Age

3 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael J. Burke, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

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UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Baylor University Medical Center - Houston

Houston, Texas, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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COG-ADVL0911

Identifier Type: -

Identifier Source: secondary_id

CDR0000663520

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL0911

Identifier Type: -

Identifier Source: org_study_id

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