Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer
Condition: Ovarian Cancer; Primary Peritoneal Cavity Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: A gene-modified virus may be able to kill tumor cells without damaging normal
      cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of an attenuated
      oncolytic measles virus therapy and oncolytic virus therapy in treating patients with
      progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer
      (measles virus vaccine therapy study closed as of 06/02/2008).
    

Detailed description: 
      OBJECTIVES:

        -  Determine the safety and toxicity of recombinant carcinoembryonic antigen
           (CEA)-expressing measles virus (MV-CEA) and oncolytic measles virus encoding thyroidal
           sodium iodide symporter (MV-NIS) in patients with progressive, recurrent, or refractory
           ovarian epithelial or primary peritoneal cavity cancer ( MV-CEA closed as of
           06/02/2008).

        -  Determine the maximum-tolerated dose of MV-CEA and MV-NIS in these patients ( MV-CEA
           closed as of 06/02/2008).

        -  Characterize viral gene expression at each dose level as manifested by CEA titers in
           these patients.

        -  Assess viremia, viral replication, and measles virus shedding or persistence after study
           therapy.

        -  Determine humoral and cellular immune response to the injected virus in these patients.

        -  Assess, preliminarily, the antitumor efficacy of this therapy, by assessing CA-125
           levels, radiographic response, and time to progression, in these patients.

        -  Determine the time course of viral gene expression and virus elimination and
           biodistribution of virally infected cells at various time points after infection with
           MV-NIS using single photon emission computed tomography (SPECT/CT) imaging.

        -  Assess viremia, viral replication, and measles virus shedding/persistence following
           intraperitoneal administration of MV-NIS.

      OUTLINE: This is a dose-escalation study.

      Patients receive recombinant carcinoembryonic antigen-expressing measles virus (MV-CEA) or
      oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) intraperitoneally
      over 30 minutes on day 1. Treatment repeats every 28 days for up to 6 courses in the absence
      of disease progression or unacceptable toxicity ( MV-CEA closed as of 06/02/2008).

      Cohorts of 3-6 patients receive escalating doses of MV-CEA until the maximum tolerated dose
      (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
      patients experience dose-limiting toxicity ( MV-CEA closed as of 06/02/2008).

      Peripheral blood mononuclear cells are collected at baseline and periodically during and
      after treatment to assess viremia. Throat gargle and urine specimens are assessed
      periodically during course 1 for viral shedding by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Peritoneal aspirate is tested at baseline and periodically during
      treatment for viral replication by RT-PCR, co-culture with Vero cells, and measles virus
      N-specific mRNA in situ hybridization.

      Patients may undergo single photon emission computed tomography (SPECT/CT) imaging at
      baseline and periodically during study.

      After completion of study therapy, patients are followed periodically for up to 15 years.

      PROJECTED ACCRUAL: A total of 46 patients will be accrued for this study.
    

Intervention name(s): carcinoembryonic antigen-expressing measles virus; oncolytic measles virus encoding thyroidal sodium iodide symporter; reverse transcriptase-polymerase chain reaction; laboratory biomarker analysis
Intervention type(s): Biological; Biological; Genetic; Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ovarian clear cell cystadenocarcinoma; ovarian endometrioid adenocarcinoma; primary peritoneal cavity cancer; ovarian mixed epithelial carcinoma; ovarian mucinous cystadenocarcinoma; ovarian serous cystadenocarcinoma; ovarian undifferentiated adenocarcinoma; recurrent ovarian epithelial cancer; Brenner tumor