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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02068794
First received: February 19, 2014
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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 recurrent ovarian cancer. Mesenchymal stem cells may be able to carry tumor-killing substances directly to ovarian cancer cells.


Condition Intervention Phase
Brenner Tumor
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mixed Epithelial Carcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Ovarian Undifferentiated Adenocarcinoma
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Procedure: mesenchymal stem cell transplantation
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Measles Virus in Patients With Recurrent Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Number and severity of adverse events (Phase I) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Tumor response defined as complete response or partial response (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Time course of viral gene expression (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 54
Study Start Date: April 2014
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 course 1 and MV-NIS infected mesenchymal stem cells IP over 30 minutes of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Procedure: mesenchymal stem cell transplantation
Given IP
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Other Name: MV-NIS
Other: laboratory biomarker analysis
Correlative studies

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 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 6 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (FEV)1 > 2 liters (Lt)
    • FEV1/forced vital capacity (FVC) > 50%
    • Residual volume (RV)/total lung capacity (TLV) < 50%
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02068794

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Evanthia Galanis    507-284-3731    galanis.evanthia@mayo.edu   
Principal Investigator: Evanthia Galanis         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Evanthia Galanis Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02068794     History of Changes
Other Study ID Numbers: MC1266, NCI-2014-00016, MC1266, P30CA015083
Study First Received: February 19, 2014
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Brenner Tumor
Carcinoma
Cystadenocarcinoma
Ovarian Neoplasms
Peritoneal Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Cystic, Mucinous, and Serous
Endocrine Gland Neoplasms
Neoplasms by Site
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases

ClinicalTrials.gov processed this record on July 28, 2014