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

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