MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) of intraperitoneal administration of an
Edmonston's strain measles virus genetically engineered to produce sodium iodine symporter
(NIS) (measles virus [MV]-NIS) in patients with recurrent ovarian cancer, delivered by
adipose tissue derived mesenchymal stem cells (MSC). (Phase I) II. To assess the 4 month
progression free survival of patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the tolerability of this regimen. (Phase II) II. To assess the response rate,
progression-free survival, and overall survival of patients treated with this regimen. (Phase
II)

TERTIARY OBJECTIVES:

I. To assess 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
versus MSC delivered MV-NIS using single-photon emission computed tomography (SPECT)/computed
tomography (CT) imaging. (Phase II) II. To assess viremia, viral replication, and measles
virus shedding/persistence following intraperitoneal administration. (Phase II) III. To
assess humoral and cellular immune response to the injected virus. (Phase II) IV. To assess
in a preliminary fashion the development of antitumor immune response. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by phase II study.

Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter
intraperitoneally (IP) over 30 minutes on day 1 of course 1 and MV-NIS infected mesenchymal
stem cells IP over 30 minutes of subsequent courses. Treatment repeats every 28 days for up
to 5 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5
years.

Inclusion Criteria:

- Must have:

- Recurrent or progressive ovarian cancer or primary peritoneal cancer after prior
treatment with platinum and taxanes

- Histologic confirmation of the original primary tumor

- Prior bilateral oophorectomy

- The following histologic epithelial cell types are eligible: serous adenocarcinoma,
endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma,
clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma,
malignant Brenner's tumor, or adenocarcinoma not otherwise specified (NOS)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelet (PLT) >= 100,000/uL

- Total bilirubin =< upper normal limit

- Aspartate aminotransferase (AST) =< 2 x upper limit of normal (ULN)

- Creatinine =< 1.5 x ULN

- Hemoglobin (Hgb) >= 9.0 g/dL

- Normal cardiac function as defined by a normal ejection fraction by multi gated
acquisition scan (MUGA) or echocardiogram

- Normal oxygen saturation at baseline ABG (arterial blood gas) testing

- The following pulmonary function tests (PFT) values in baseline:

- Forced expiratory volume in one second (FEV1) > 80% predicted

- FEV1/forced vital capacity (FVC) > 80%

- Residual volume (RV)/total lung capacity (TLV) >= 80%

- Provide informed written consent

- Willing to return to Mayo Clinic Rochester for follow-up

- Life expectancy >= 12 weeks

- Willing to provide all biologic specimens as required by the protocol

- Measurable disease by exam or CT scan, or for patients with cancer antigen (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

- Cluster of differentiation (CD)4 count >= 200/uL 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 months from completion of primary
(adjuvant) chemotherapy

- Active infection =< 5 days prior to registration

- History of tuberculosis or history of tuberculosis skin test (PPD) positivity

- History of other malignancy =< 5 years prior to registration except for non-melanoma
skin cancer, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS)

- Any of the following prior therapies:

- Chemotherapy =< 3 weeks prior to registration

- Immunotherapy =< 4 weeks prior to registration

- Biologic therapy =< 4 weeks prior to registration

- Extensive abdominal surgery if it includes enterotomy(ies) =< 3 weeks prior to
registration; this criterion does not apply to placement of the peritoneal
Port-A-Cath or lysis of adhesions at the time of registration

- Any viral or gene therapy prior to registration

- Radiation therapy to the abdomen or pelvis

- 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 supraventricular tachycardia [SVT])

- Other cardiac or pulmonary disease that, at the investigators discretion, can impair
treatment safety

- Requiring blood product support

- Central nervous system (CNS) metastases or seizure disorder

- Human immunodeficiency virus (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-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- Intra-abdominal disease > 8 cm in diameter at the time of registration, intrahepatic
disease, or disease beyond the abdominal cavity; patients with intra-abdominal lymph
node involvement are eligible based on biodistribution data indicating viral
dissemination to lymph nodes following intraperitoneal administration

- 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

- Any other pathology or condition where the principle investigator may deem to
negatively impact treatment safety