A Phase 1 Dose Escalation Study of Reolysin, a Replication Competent Reovirus, in Pediatric Patients With Relapsed or Refractory Solid Tumors

Inclusion Criteria:

- Diagnosis of relapsed or refractory solid tumors

- Must have had histologic verification of malignancy at original diagnosis or
relapse

- Disease for which there is no known curative therapy or therapy proven to
prolong survival with an acceptable quality of life

- No primary central nervous system (CNS) tumors or lymphomas

- Measurable or evaluable disease

- No known germline mutations affecting Ras activation (e.g., cardio-facial-cutaneous
syndrome, Noonan syndrome, Costello syndrome)

- No known metastatic CNS disease

- Karnofsky performance status (PS) 50-100% for patients > 16 years of age OR Lansky PS
50-100% for patients ≤ 16 years of age

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Platelet count ≥ 100,000/mm³ (transfusion independent, defined as ≥ 7 days since
platelet transfusion prior to enrollment)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR
serum creatinine based on age and/or gender as follows:

- 0.8 mg/dL (3 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal (ULN)

- Alanine aminotransferase (ALT) =< 110 U/L (ULN for ALT is 45 U/L)

- Serum albumin ≥ 2 g/dL

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated
radionuclide study

- Pulmonary function tests (PFTs), including diffusion capacity of carbon monoxide
(DLCO), normal for patients with respiratory symptoms (e.g., dyspnea at rest, known
requirement for supplemental oxygen)

- Full PFTs not required for patients without respiratory symptoms

- Seizure disorder allowed provided it is well controlled with anticonvulsants

- Nervous system disorders (NCI CTCAE v. 4) resulting from prior therapy must be ≤
grade 2

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No uncontrolled infections

- No chronic diarrhea, urinary incontinence during the day or at night, or patients who
are not completely toilet trained

- No household contacts (living with patient during the 4 weeks of treatment) who are
pregnant, immunosuppressed, or infants < 3 months of age

- No patients who, in the opinion of the investigator, may not be able to comply with
the safety monitoring requirements of the study

- No known HIV infection, hepatitis B or C, or any pre-existing infection

- Recovered from acute toxic effects of all prior anti-cancer chemotherapy and
immunizations

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

- At least 14 days since prior long-acting growth factor (e.g., Neulasta) or ≥ 7 days
since short-acting growth factor

- At least 7 days since prior biologic agent (anti-neoplastic agent)

- At least 16 weeks since prior immunotherapy (e.g., tumor vaccines)

- At least 3 half-lives since prior monoclonal antibody

- At least 2 weeks since prior palliative radiotherapy (small port)

- At least 24 weeks since prior total body irradiation, craniospinal radiotherapy,
or ≥ 50% of radiotherapy to the pelvis

- At least 6 weeks since other prior substantial bone marrow radiation

- At least 12 weeks since prior stem cell transplant or infusion with no evidence of
active graft-vs-host disease

- More than 7 days since prior viral immunizations, including influenza vaccine

- Patients may not receive any viral immunizations after enrolling on study and
for ≥ 28 days after their last planned Reolysin infusion

- More than 7 days since prior corticosteroids, immune modulators, or antiviral therapy

- Intravenous immune globulin (IVIG) may not be given within 2 weeks of Reolysin
administration

- No prior viral-based anti-neoplastic therapies

- No other concurrent investigational drugs

- No other concurrent anticancer agents including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy

- No concurrent cyclosporine, tacrolimus, or other agents to prevent either
graft-versus-host disease after bone marrow transplant or organ rejection after
transplant

- No concurrent corticosteroids (with the exception of hydrocortisone as a treatment
for anaphylaxis), immune modulators, antiviral therapy, or IVIG

- No concurrent acetaminophen