Clinical Trials /

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

NCT02068794

Description:

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.

Related Conditions:
  • Ovarian Carcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Seromucinous Carcinoma
  • Ovarian Serous Adenocarcinoma
  • Ovarian Transitional Cell Carcinoma
  • Primary Peritoneal Carcinoma
  • Primary Peritoneal Clear Cell Carcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
  • Primary Peritoneal Transitional Cell Carcinoma
  • Primary Peritoneal Undifferentiated Carcinoma
  • Undifferentiated Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MC1266
  • SECONDARY ID: NCI-2014-00016
  • SECONDARY ID: MC1266
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02068794

Conditions

  • Malignant Ovarian Brenner Tumor
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Seromucinous Carcinoma
  • Ovarian Serous Adenocarcinoma
  • Ovarian Transitional Cell Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Undifferentiated Ovarian Carcinoma

Interventions

DrugSynonymsArms
Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide SymporterMV-NISTreatment (MV-NIS infected mesenchymal stem cells)

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (MV-NIS infected mesenchymal stem cells)ExperimentalPatients 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.
  • Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Eligibility 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Maximum grade for each type of toxicity (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measure: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
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Measure:Tumor response defined as complete response or partial response (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

May 27, 2020