Phase I Trial of Intraperitoneal Administration of a) a CEA-Expressing Derivative, and b) a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer
- 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
- 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
- Assess viremia, viral replication, and measles virus shedding or persistence after
- 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
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.
Masking: Open Label, Primary Purpose: Treatment
Number of toxicity incidents
Evanthia Galanis, MD
United States: Food and Drug Administration
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