Primary Outcome Measures:
- Number of toxicity incidents [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Number of responses (complete and partial, stable and progressive disease) [ Designated as safety issue: No ]
- CA-125 levels [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
- Laboratory correlates [ Designated as safety issue: No ]
OBJECTIVES:
- Determine the safety and toxicity of recombinant carcinoembryonic antigen (CEA)-expressing measles virus (MV-CEA) in patients with progressive, recurrent, or refractory ovarian epithelial or primary peritoneal cavity cancer.
- Determine the maximum tolerated dose of MV-CEA in these patients.
- 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.
OUTLINE: This is a dose-escalation study.
Patients receive recombinant carcinoembryonic antigen-expressing measles virus (MV-CEA) 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.
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.
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.
After completion of study therapy, patients are followed periodically for up to 15 years.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.