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

• ClinicalTrials.gov Identifier: NCT00314925
• Recruitment Status: Unknown
• First Posted: April 17, 2006
• Last Update Posted: February 25, 2010
• Sponsor: Neotropix
• Information provided by: Neotropix

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoid; Neuroendocrine	Drug: Seneca Valley Virus (biological agent)	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: April 2006
• Estimated Primary Completion Date: December 2008
• Estimated Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	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; Other Name: SVV-001

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicity and determination of phase II dose [ Time Frame: Within 28 days of treatment administration ]

Secondary Outcome Measures :

1. Number of responses according to RECIST criteria [ Time Frame: 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 ]
2. Limited pharmacokinetics, biodistribution and elimination [ Time Frame: Until 2 consecutive negative viral assays ]
3. Limited evaluation of occurrence of neutralizing antibody [ Time Frame: Baseline and at Week 2, Day 1 following therapy ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Cancer Centers of Florida

Ocoee, Florida, United States, 34761

United States, Indiana

Central Indiana Cancer Centers

Indianapolis, Indiana, United States, 46219

United States, Maryland

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

United States, New York

New York Oncology Hematology P.C.

Albany, New York, United States, 12208

United States, Ohio

Dayton Oncology & Hematology, P.A .

Kettering, Ohio, United States, 45409

United States, South Carolina

Cancer Centers of the Carolinas

Greenville, South Carolina, United States, 29605

United States, Texas

Mary Crowley Research Center

Dallas, Texas, United States, 75201

Tyler Cancer Center

Tyler, Texas, United States, 75702

United States, Virginia

Virginia Oncology Associates

Norfolk, Virginia, United States, 23502

United States, Washington

Northwest Cancer Specialists - Vancouver Cancer Center

Vancouver, Washington, United States, 98684

Sponsors and Collaborators

Neotropix

Investigators

• Study Chair: Rudin Charles, MD, PhD; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

More Information

Additional Information:

website of sponsor 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Margaret Valnoski, President, Theradex, Inc.
• ClinicalTrials.gov Identifier: NCT00314925
• Other Study ID Numbers: N05-10564
• First Posted: April 17, 2006
• Last Update Posted: February 25, 2010
• Last Verified: February 2010

Keywords provided by Neotropix:

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

Additional relevant MeSH terms:

Carcinoid Tumor; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue