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

Study Description

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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:

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	22 participants
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

Arms and Interventions

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

Outcome Measures

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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 ]

Eligibility Criteria

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

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

Contacts and Locations

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Locations

United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital of Orange County
Orange, California, United States, 92868
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60611
United States, Indiana
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 2115
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109-0286
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St. Louis, Missouri, United States, 63110
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Michael J. Burke, MD	Masonic Cancer Center, University of Minnesota

More Information

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Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT01048892 History of Changes
Other Study ID Numbers:	ADVL0911; COG-ADVL0911; CDR0000663520 ( Other Identifier: Clinical Trials.gov )
First Posted:	January 14, 2010
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:

Neuroblastoma; Kidney Neoplasms; Carcinoma, Renal Cell; Rhabdomyosarcoma; Carcinoid Tumor; Retinoblastoma; Malignant Carcinoid Syndrome; Gastrointestinal Neoplasms; Adrenocortical Carcinoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type	Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neuroendocrine Tumors