Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features

Carcinoid Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00314925
• Other study ID #: N05-10564
• Status: Active, not recruiting
• Phase: Phase 1
• First received: April 13, 2006
• Last updated: February 23, 2010
• Start date: April 2006
• Est. completion date: December 2008

Study information

• Verified date: February 2010
• Source: Neotropix
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid
• Neuroendocrine

Intervention

Drug:
• Seneca Valley Virus (biological agent)
Dose escalation (starting at 1 × 10^7 vp/kg), IV (in the vein) over 1 hour in a single administration

Locations

Country	Name	City	State
United States	New York Oncology Hematology P.C.	Albany	New York
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Mary Crowley Research Center	Dallas	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Dayton Oncology & Hematology, P.A .	Kettering	Ohio
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Centers of Florida	Ocoee	Florida
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists - Vancouver Cancer Center	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Neotropix

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicity and determination of phase II dose		Within 28 days of treatment administration	Yes
Secondary	Number of responses according to RECIST criteria		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	No
Secondary	Limited pharmacokinetics, biodistribution and elimination		Until 2 consecutive negative viral assays	No
Secondary	Limited evaluation of occurrence of neutralizing antibody		Baseline and at Week 2, Day 1 following therapy	No

External Links

•   website of sponsor