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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I/II Trial of Intraperitoneal Administration of Adipose Tissue Derived Mesenchymal Stem Cells Infected With a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measl

Brief Summary: 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 cancer that has come back. Mesenchymal stem cells may be able to carry tumor-killing substances directly to ovarian cancer cells.

Detailed Summary:

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 c
Sponsor: Mayo Clinic

Current Primary Outcome:

• MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: 28 days ]
• Number and severity of adverse events (Phase I) [ Time Frame: Up to 5 years ]
  All adverse events (overall, and by dose-level) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.
• Overall toxicity incidence (Phase I) [ Time Frame: Up to 5 years ]
  Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
• Proportion of patients alive and progression-free at 4 months (Phase II) [ Time Frame: At 4 months ]
  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.
• Toxicity profiles by dose level and patient (Phase I) [ Time Frame: 28 days ]
  Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

Original Primary Outcome:

• MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: 28 days ]
• Number and severity of adverse events (Phase I) [ Time Frame: Up to 5 years ]
  All adverse events (overall, and by dose-level) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.
• Overall toxicity incidence (Phase I) [ Time Frame: Up to 5 years ]
  Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
• Toxicity profiles by dose level and patient (Phase I) [ Time Frame: 28 days ]
  Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
• Proportion of patients alive and progression-free at 4 months (Phase II) [ Time Frame: At 4 months ]
  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.

Current Secondary Outcome:

• Maximum grade for each type of toxicity (Phase II) [ Time Frame: Up to 5 years ]
• Overall survival (Phase II) [ Time Frame: Length of time from study registration to date of death due to any cause or last follow up assessed up to 5 years ]
  The distribution of survival time will be estimated using the method of Kaplan-Meier.
• Progression free survival (Phase II) [ Time Frame: Length of time from study registration to the first of either death due to any cause or progression assessed up to 5 years ]
  The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
• Tumor response defined as complete response or partial response (Phase II) [ Time Frame: Up to 5 years ]

Original Secondary Outcome:

• Tumor response defined as complete response or partial response (Phase II) [ Time Frame: Up to 5 years ]
• Overall survival (Phase II) [ Time Frame: Length of time from study registration to date of death due to any cause or last follow up assessed up to 5 years ]
  The distribution of survival time will be estimated using the method of Kaplan-Meier.
• Progression free survival (Phase II) [ Time Frame: Length of time from study registration to the first of either death due to any cause or progression assessed up to 5 years ]
  The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
• Maximum grade for each type of toxicity (Phase II) [ Time Frame: Up to 5 years ]

Information By: Mayo Clinic

Dates:
Date Received: February 19, 2014
Date Started: March 2014
Date Completion: March 10, 2021
Last Updated: March 14, 2017
Last Verified: June 2016