Phase I Dose-Escalation Study of Seneca Valley Virus (SVV-001), a Replication-Competent Picornavirus, in Patients With Advanced Solid Tumors With Neuroendocrine Features

Inclusion Criteria:

- Patients must have a histologically confirmed solid tumor (including carcinoid) with
neuroendocrine features (i.e., expression of >= 1 of the following 3 markers:
synaptophysin, chromogranin A, or CD56) that is metastatic or unresectable and for
which standard curative or palliative measures do not exist or are no longer
effective.

- Patients must show evidence of disease progression in the three months prior to
treatment with SVV-001.

- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of SVV-001 in patients <18 years of age, children are excluded from this
study. Children may be eligible for future pediatric Phase I single-agent trials.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Life expectancy >= 24 weeks.

- Adequate bone marrow, hepatic, and renal function as defined below:

- absolute lymphocyte count >= 1,000/ul

- absolute neutrophil count >= 1,500/ul

- platelets >= 100,000/ul

- AST/ALT <= 2.5 x upper limit of normal (ULN) or <= 5 x ULN if liver metastases
present

- total bilirubin <= 1.5 x upper limit of normal

- creatinine <= 1.5 x upper limit of normal OR

- creatinine clearance (calculated) <= 60 mL/min/1.73 m2 for patients with
creatinine > 1.5 x upper limit of normal.

- Women must have been surgically sterilized or be post-menopausal.

- Men must agree to use adequate contraception (barrier method of birth control;
abstinence) prior to study entry and for up to 6 months.

- Ability to understand and the willingness to sign a written informed consent
document.

- Patients must have oxygen saturation of at least 95% on room air.

- Patients must have measurable disease by RECIST (CT and/or MRI).

Exclusion Criteria:

- Patients with small cell histology.

- Patients who have been hospitalized for emergent conditions requiring inpatient
evaluation, treatment or procedure during the 30 days prior to entry on study. In
addition, emergent conditions requiring inpatient evaluation, treatment or procedure
must have resolved or be medically stable and not severe for 30 days prior to entry
on study.

- Use of chemotherapy or radiotherapy within 4 weeks of initiation of SVV-001, or
continued > Grade 1 adverse events, excluding alopecia, due to agents administered
more than 4 weeks earlier.

- Patients with clinically evident Human Immuno-deficiency Virus (HIV), Hepatitis B
Virus (HBV) or Hepatitis C Virus (HCV) infection.

- Patients with > Grade 1 peripheral neuropathy (CTCAE version 3.0).

- Concurrent use of any other investigational agents.

- Presence of or history of central nervous system metastasis.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pre-menopausal women who have not been surgically sterilized. Although SVV-001 has no
affect on the ovaries from a toxicological perspective, SVV-001 RNA is present in the
ovaries at 12 weeks in animals that were administered high and medium doses. No
pre-clinical reproductive tests have been conducted with SVV-001.