Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Phase 1

Completed

Conditions: Primary Peritoneal Cavity Cancer
Ovarian Cancer

Interventions: 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

Registration Number: NCT00408590

Lead Sponsor: Mayo Clinic

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 37

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Arm	reverse transcriptase-polymerase chain reaction	-
Experimental Arm	carcinoembryonic antigen-expressing measles virus	-
Experimental Arm	oncolytic measles virus encoding thyroidal sodium iodide symporter	-
Experimental Arm	laboratory biomarker analysis	-

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity	up to 12 months after last treatment	If one patient experiences a Dose limiting Toxicity(DLT), up to three additional patients will be treated at the same dose level. If DLT is observed in only one of six patients treated at a given dose level, the next cohort of three patients will be treated at the next higher dose level. If two or more patients experience DLT at a particular dose level, then the dose escalation will cease and any subsequent patients will be treated at a lower dose level. Thus finding the Max tolerated dose

Secondary Outcome Measures

Name	Time	Method
Time to Progression	up to 12 months after last treatment	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Number of Responses (Complete and Partial, Stable and Progressive Disease)	up to 12 months after last treatment	Responses will be summarized separately for the MV-CEA virus and MV-NIS virus by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. CA125 levels and time to progression will also be summarized descriptively. Modified Response Evaluation Criteria in Solid Tumors(RECIST v1.0) criteria will be used. For target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter(LD) of target lesions; Progression (PD): As least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD
Change in CA-125 Levels From Baseline to Last Recorded Value (up to 18 Months)	baseline and up to 18 months	CA-125 tests are measured in units per milliliter (U/mL) and taken every cycle (up to 6-28 day cycles) during treatment and every three months up to 12 months after treatment. The change in CA-125 is calculated as the baseline CA-125 value subtracted by the last recorded value of CA-125 (up to 18 months from baseline.