• Number of toxicity incidents [ Designated as safety issue: Yes ]
• Maximum tolerated dose [ Designated as safety issue: Yes ]

• Number of toxicity incidents
• Maximum tolerated dose

• 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 ]

• Number of responses (complete and partial, stable and progressive disease)
• CA-125 levels
• Time to progression
• Laboratory correlates

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 oncolytic virus therapy in treating patients with progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer.

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.

• Ovarian Cancer
• Peritoneal Cavity Cancer

• Biological: carcinoembryonic antigen-expressing measles virus
• Genetic: reverse transcriptase-polymerase chain reaction

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial cancer or primary peritoneal cavity cancer

  • Progressive, recurrent, or refractory after prior treatment with platinum and taxol compounds

  • Any of the following histologic epithelial cell types allowed:

    • Serous adenocarcinoma
    • Endometrioid adenocarcinoma
    • Mucinous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial carcinoma
    • Transitional cell carcinoma
    • Malignant Brenner's tumor
    • Adenocarcinoma not otherwise specified
• Has undergone prior bilateral oophorectomy

• No known standard therapy that is potentially curative or capable of extending life expectancy exists

  • No first relapse and recurrence > 6 months after completion of primary (adjuvant) chemotherapy
• Measurable disease by exam or CT scan OR nonmeasurable disease on imaging (CA-125 elevation or microscopic residual disease)
• No intra-abdominal disease > 8 cm in diameter, intrahepatic disease, or disease beyond the abdominal cavity
• Carcinoembryonic antigen levels normal (< 5 mg/mL)
• CD4-positive T-cell count ≥ 200/mm³ OR ≥ 15% of peripheral blood lymphocytes
• No epithelial tumors of low malignant potential, stromal tumors, or germ cell tumors of the ovary
• No CNS metastases

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks
• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin normal
• AST ≤ 2 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 times ULN
• Hemoglobin ≥ 9.0 g/dL
• Must have anti-measles immunity as demonstrated by serum IgG anti-measles antibody levels of ≥ 20.0 EU/mL as determined by enzyme immunoassay
• Must have positive delayed-type hypersensitivity
• No active infection within the past 5 days
• No history of positivity for tuberculosis or purified protein derivative (PPD) of tuberculin
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No New York Heart Association class III or IV heart disease
• No requirement for blood product support
• No seizure disorder
• No HIV positivity
• No history of other immunodeficiency
• No history of chronic hepatitis B or C
• No exposure to household contacts ≤ 15 months of age or household contacts with known immunodeficiency
• No allergy to measles vaccine or history of severe reaction to prior measles vaccination

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy and recovered
• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• More than 3 weeks since prior extensive abdominal surgery (including enterotomies) except placement of peritoneal port-a-cath or lysis of adhesions
• No prior viral or gene therapy
• No prior organ transplantation
• No other concurrent chemotherapy, immunotherapy, or radiotherapy
• No other concurrent investigational therapies
• No concurrent medications that could interfere with study treatment

• No concurrent oral or systemic corticosteroids

  • Concurrent topical or inhaled steroids allowed
• No concurrent participation in another clinical study involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, or gene therapy) for symptom control of therapeutic intent