Recombinant Measles Virus Vaccine Therapy and 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) 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.

Inclusion criteria:

- Age ≥ 18 years.

- Must have persistent, recurrent or progressive ovarian cancer or primary peritoneal
cancer after prior treatment with platinum and taxol compounds. Histologic
confirmation of the original primary tumor is required. Prior bilateral oophorectomy
is required.

- Patients with the following histologic epithelial cell types are eligible: Serous
adenocarcinoma, endometroid adenocarcinoma, mucinous adenocarcinoma, undifferentiated
carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell
carcinoma, malignant Brenner's Tumor, or adenocarcinoma NOS

- The following laboratory values obtained ≤7 days prior to registration:

- ANC ≥ 1500/μL

- PLT ≥ 100,000/μL

- Total bilirubin ≤ upper normal limit

- AST ≤ 2 x ULN

- Creatinine ≤ 1.5 x ULN

- Hgb ≥ 9.0 g/dL

- Ability to provide informed consent.

- Willingness to return to Mayo Clinic Rochester for follow-up.

- Life expectancy ≥ 12 weeks.

- Must have anti-measles immunity as demonstrated by serum IgG anti-measles antibody
levels of ≥ 20.0 EU/ml as determined by Enzyme Immunoassay (Diamedix, FL).

- Must have normal serum CEA levels (<5 mg/ml) both at the time of study entry and in
any prior testing. (NOTE: Not applicable for the MV-NIS cohort.)

- Willingness to provide all biologic specimens as required by the protocol.

- Measurable disease by exam or CT scan, or, for patients with CA-125 elevation or with
microscopic residual but without measurable disease on imaging, willingness to undergo
laparoscopy for evaluation of treatment effect if no radiographic progression after 6
treatment cycles.

- CD4 count ≥200/μL or ≥15% of peripheral blood lymphocytes

Exclusion criteria:

- Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of
the ovary.

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy. Subjects will be excluded if this is
their first relapse and they have recurred >6 mo from completion of primary (adjuvant)
chemotherapy.

- ECOG performance status (PS) 3 or 4.

- Active infection ≤5 days prior to registration.

- History of tuberculosis or history of PPD positivity.

- History of other malignancy ≤5 years except for non-melanoma skin cancer or carcinoma
in situ of the cervix.

- Any of the following prior therapies:

- Chemotherapy ≤ 3 weeks prior to study entry

- Immunotherapy ≤ 4 weeks prior to study entry

- Biologic therapy ≤ 4 weeks prior to study entry

- Extensive abdominal surgery if it includes enterotomy(ies) <3 weeks prior to
study entry. This criterion does not apply to placement of the peritoneal
port-a-cath or lysis of adhesions at the time of study entry.

- Any viral or gene therapy prior to study entry

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment.

- New York Heart Association classification III or IV, known symptomatic coronary artery
disease, or symptoms of coronary artery disease on systems review, or known cardiac
arrhythmias (atrial fibrillation or SVT).

- Requiring blood product support.

- CNS metastases or seizure disorder.

- HIV-positive test result, or history of other immunodeficiency.

- History of organ transplantation.

- History of chronic hepatitis B or C.

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-FDA-approved indication and in the
context of a research investigation).

- Any concurrent medications which could interfere with the trial.

- Intra-abdominal disease > 8 cm in diameter at the time of registration, intrahepatic
disease, or disease beyond the abdominal cavity.

- Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled
steroids.

- Exposure to household contacts ≤15 months old or household contact with known
immunodeficiency.

- Allergy to measles vaccine or history of severe reaction to prior measles vaccination.

- Allergy to iodine. This does not include reactions to intravenous contrast materials.