Clinical trial NCT00314925: Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features
Official title: Phase I Dose-Escalation Study of Seneca Valley Virus (SVV-001), a Replication-Competent Picornavirus, in Patients With Advanced Solid Tumors With Neuroendocrine Features
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Carcinoid
Neuroendocrine
Keywords: advanced carcinoma
carcinoid
neuroendocrine features
oncolytic virus
phase I study
dose escalation study
rhabdomyosarcoma
alveolar rhabdomyosarcoma
medulloblastoma
rhabdoid
glioblastoma
ewing's sarcoma
pediatric oncologies
neuroblastoma
wilms' tumor
retinoblastoma
Large cell lung cancer
Lead sponsor: Neotropix
Sponsor class: INDUSTRY
First posted: 2006-04-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to determine if Seneca Valley Virus may be administered safely to patients with certain types of advanced cancer.

Detailed description: This is the first study in man of Seneca Valley Virus, a virus which seeks and kills certain tumors in non-human model systems. Subjects in this trial will be patients with advanced cancer displaying certain specified neuroendocrine features, pathologically; they will have exhausted standard methods of treatment for their tumor. The primary purpose of the trial is to determine if the virus may be administered safely. Additional purposes are to learn about the distribution of the virus in the body, the elimination of the virus from the body, the immune response to the virus and whether the virus might have some beneficial effects upon the tumors which the patients have. The first patients will be treated with low amounts of virus and subsequent patients may receive higher amounts. At the end of the trial, it is intended to select a dose for further study.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity and determination of phase II dose
timeFrame: Within 28 days of treatment administration
Secondary outcomes:
measure: Number of responses according to RECIST criteria
timeFrame: Baseline; at Week 7, Day 7 following therapy and then confirmation scan at least 4 weeks later, if required; and every 2 months for up to 6 months, if required
measure: Limited pharmacokinetics, biodistribution and elimination
timeFrame: Until 2 consecutive negative viral assays
measure: Limited evaluation of occurrence of neutralizing antibody
timeFrame: Baseline and at Week 2, Day 1 following therapy
Other outcomes:
Locations:
city: Ocoee
country: United States
facility: Cancer Centers of Florida
state: Florida
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Albany
country: United States
facility: New York Oncology Hematology P.C.
state: New York
city: Kettering
country: United States
facility: Dayton Oncology & Hematology, P.A .
state: Ohio
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Research Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver Cancer Center
state: Washington
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Rudin Charles, MD, PhD
role: STUDY_CHAIR
References:
citation: Venkataraman S, Reddy SP, Loo J, Idamakanti N, Hallenbeck PL, Reddy VS. Crystallization and preliminary X-ray diffraction studies of Seneca Valley virus-001, a new member of the Picornaviridae family. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Apr 1;64(Pt 4):293-6. doi: 10.1107/S1744309108006921. Epub 2008 Mar 21.