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



Status:Recruiting
Conditions:Cancer, Cancer, Brain Cancer, Kidney Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:3 - 21
Updated:3/1/2014
Start Date:September 2009

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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

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.

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.

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
We found this trial at
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9000 W Wisconsin Ave
Milwaukee, Wisconsin 53226
(414) 266-2000
Midwest Children's Cancer Center at Children's Hospital of Wisconsin We are the region's only independent...
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Milwaukee, WI
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1540 East Hospital Drive
Ann Arbor, Michigan 48109
734-936-4000
C.S. Mott Children's Hospital at University of Michigan Medical Center Behind the doors of C.S....
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Ann Arbor, MI
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1802 6th Avenue South
Birmingham, Alabama 35294
(205) 934-4011
UAB Comprehensive Cancer Center One of the nation’s leading cancer research and treatment centers, the...
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Birmingham, AL
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450 Brookline Ave
Boston, Massachusetts 2215
(617) 632-3000
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Founded in 1997, Dana-Farber/Harvard Cancer Center (DF/HCC) was...
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Boston, MA
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas From its...
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262 Danny Thomas Pl
Memphis, Tennessee 38105
(901) 495-3300
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
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Memphis, TN
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425 E River Pkwy # 754
Minneapolis, Minnesota 55455
612-624-2620
Masonic Cancer Center at University of Minnesota The Masonic Cancer Center was founded in 1991....
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Minneapolis, MN
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701 West 168th Street
New York, New York 10032
(212) 851-4680
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center The Herbert Irving Comprehensive Cancer...
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New York, NY
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
Children's Hospital of Pittsburgh of UPMC UPMC is one of the leading nonprofit health systems...
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1600 Divisadero Street
San Francisco, California 94115
888.689.8273
UCSF Helen Diller Family Comprehensive Cancer Center UCSF’s long tradition of excellence in cancer research...
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4800 Sand Point Way Northeast
Seattle, Washington 98105
(206) 987-2000
Children's Hospital and Regional Medical Center - Seattle Seattle Children
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2515 N Clark St
Chicago, Illinois 60614
(312) 227-6060
Children's Memorial Hospital, Chicago Ann & Robert H. Lurie Children
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One Baylor Plaza
Houston, Texas 77030
(713) 798-4951
Baylor University Medical Center - Houston Baylor University Medical Center in Dallas began in 1903...
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705 Riley Hospital Drive
Indianapolis, Indiana 46202
317.944.2060
Riley's Children Cancer Center at Riley Hospital for Children The Riley Hospital for Children Cancer...
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111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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