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MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer

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ClinicalTrials.gov Identifier: NCT02068794
Recruitment Status : Recruiting
First Posted : February 21, 2014
Last Update Posted : April 8, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE February 19, 2014
First Posted Date  ICMJE February 21, 2014
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE March 31, 2014
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 24, 2020)
  • Maximum tolerated dose (MTD) (Phase I) [ Time Frame: 28 days ]
    Will be 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).
  • 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 at 12 months (Phase II) [ Time Frame: At 12 months after study registration ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2020)
  • Tumor response (Phase II) [ Time Frame: Up to 5 years ]
    Will be defined as complete response or partial response.
  • Rate of 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 at 4 months ]
    Kaplan-Meier survival curves and logrank tests will be used to estimate the progression-free time distributions of the study patients and study patient subsets defined by disease and/or correlative characteristics.
  • 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 Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall survival in patients treated with oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS)/mesenchymal stem cells (MSC) will be made to patients enrolled on the prior MV-carcinoembryonic antigen (CEA) and MV-NIS trial in an exploratory manner.
  • 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 at 5 years ]
    The distribution of progression-free survival will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall progression free survival 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.
  • Maximum grade for each type of toxicity (Phase II) [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
  • 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 ]
Current Other Pre-specified Outcome Measures
 (submitted: November 24, 2020)
  • Time course of viral gene expression (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Virus elimination and biodistribution of virally infected cells by single photon emission computed tomography imaging (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Incidence of viremia (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Incidence of viral replication (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Measles virus shedding/persistence following intraperitoneal administration (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Humoral immune response to the injected virus (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Cellular immune response to the injected virus (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
  • Antitumor immune response (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Original Other Pre-specified Outcome Measures
 (submitted: February 19, 2014)
  • Time course of viral gene expression (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Virus elimination and biodistribution of virally infected cells by single photon emission computed tomography imaging (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Incidence of viremia (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Incidence of viral replication (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Measles virus shedding/persistence following intraperitoneal administration (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Humoral immune response to the injected virus (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Cellular immune response to the injected virus (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Antitumor immune response (Phase II) [ Time Frame: Up to 5 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
 
Descriptive Information
Brief Title  ICMJE MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Official Title  ICMJE 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 Measles Virus in Patients With Recurrent Ovarian Cancer
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, 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.
Detailed Description

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.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fallopian Tube Clear Cell Adenocarcinoma
  • Fallopian Tube Endometrioid Adenocarcinoma
  • Fallopian Tube Mucinous Adenocarcinoma
  • Fallopian Tube Serous Adenocarcinoma
  • Fallopian Tube Transitional Cell Carcinoma
  • Fallopian Tube Undifferentiated Carcinoma
  • Malignant Ovarian Brenner Tumor
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Seromucinous Carcinoma
  • Ovarian Serous Adenocarcinoma
  • Ovarian Transitional Cell Carcinoma
  • Ovarian Undifferentiated Carcinoma
  • Primary Peritoneal Serous Adenocarcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Procedure: Mesenchymal Stem Cell Transplantation
    Given IP
  • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    Given IP
    Other Name: MV-NIS
Study Arms  ICMJE Experimental: Treatment (MV-NIS infected mesenchymal stem cells)
Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and MV-NIS infected 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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Procedure: Mesenchymal Stem Cell Transplantation
  • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 24, 2020)
57
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2014)
54
Estimated Study Completion Date  ICMJE March 1, 2022
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have:

    • Recurrent or progressive ovarian cancer, primary peritoneal cancer or fallopian tube 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 (obtained =< 7 days prior to registration)
  • Platelet (PLT) >= 100,000/uL (obtained =< 7 days prior to registration)
  • Total bilirubin =< upper normal limit (obtained =< 7 days prior to registration)
  • Aspartate aminotransferase (AST) =< 2 x upper limit of normal (ULN) (obtained =< 7 days prior to registration)
  • Creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)
  • Hemoglobin (Hgb) >= 9.0 g/dL (obtained =< 7 days prior to registration)
  • Normal cardiac function as defined by a normal ejection fraction by multi gated acquisition scan (MUGA) or echocardiogram
  • 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
  • CD4 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 purified protein derivative (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02068794
Other Study ID Numbers  ICMJE MC1266
NCI-2014-00016 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1266 ( Other Identifier: Mayo Clinic in Rochester )
P30CA015083 ( U.S. NIH Grant/Contract )
P50CA136393 ( U.S. NIH Grant/Contract )
P50CA083639 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Evanthia Galanis Mayo Clinic
PRS Account Mayo Clinic
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP