Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer
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).
Primary Peritoneal Cavity Cancer
Biological: carcinoembryonic antigen-expressing measles virus
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Number of toxicity incidents [ Designated as safety issue: Yes ]
- Maximum-tolerated dose [ Designated as safety issue: Yes ]
- 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 ]
|Study Start Date:||April 2004|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408590
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Evanthia Galanis, MD||Mayo Clinic|