This phase I/II trial studies the side effects and best dose of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) infected mesenchymal stem cells and to see how well it works in treating patients with ovarian, primary peritoneal or fallopian tube cancer that has come back. Mesenchymal stem cells may be able to carry tumor-killing substances directly to ovarian, primary peritoneal and fallopian tube cancer cells.
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 12 month overall 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 4 month progression free survival of patients treated with this regimen. (Phase II) III. To assess the response rate, progression-free survival, and overall survival of patients treated with this regimen. (Phase II) TRANSLATIONAL 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 cycle 1 and MV-NIS infected mesenchymal stem cells (MSC) (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Correlative studies
Given IP
Given IP
Undergo ECHO
Undergo MUGA
Undergo blood sample collection
Undergo chest X-ray
Undergo SPECT/CT
Undergo CT
Undergo MRI
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Count of Participants That Experience a DLT
Maximum tolerated dose will be defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients).
Time frame: 28 days
Overall Survival at 12 Months
The proportion of patients that were followed and alive at 12 months post registration.
Time frame: 12 months
Tumor Response (Phase II)
Will be defined as complete response or partial response.
Time frame: Up to 5 years
4 Month Progression Free Survival Rate
Defined as the proportion of patients alive and progression free at 4 months.
Time frame: 4 months
Overall Survival (Phase II)
Defined as the length of time from study registration to date of death due to any cause. The distribution of survival time will be estimated using Kaplan-Meier survival curves and logrank tests.
Time frame: Up to 5 years
Progression Free Survival (Phase II)
Progression-free survival (PFS) is defined as the length of time from study registration to the first of either death due to any cause or progression. The distribution of PFS will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall PFS in patients treated with MV-NIS/MSC will be made to patients enrolled on the prior MV-CEA and MV-NIS trial in an exploratory manner.
Time frame: Up to 5 years
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