Clinical Trials /

Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery

NCT02700230

Description:

This phase I trial studies the side effects and the best dose of a vaccine therapy in treating patients with malignant peripheral nerve sheath tumor that cannot be removed by surgery (unresectable) or has come back after a period of improvement (recurrent). Vaccines made from a gene-modified virus may kill tumor cells expressing a gene called neurofibromin 1 (NF1) without affecting surrounding normal cells and may also help the body build an effective immune response to kill tumor cells.

Related Conditions:
  • Malignant Peripheral Nerve Sheath Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery
  • Official Title: Phase I Trial of Intratumoral Administration of a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

Clinical Trial IDs

  • ORG STUDY ID: MC1372
  • SECONDARY ID: NCI-2016-00179
  • SECONDARY ID: MC1372
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02700230

Conditions

  • Metastatic Malignant Peripheral Nerve Sheath Tumor
  • Neurofibromatosis Type 1
  • Recurrent Malignant Peripheral Nerve Sheath Tumor

Interventions

DrugSynonymsArms
Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide SymporterMV-NISTreatment (MV-NIS)

Purpose

This phase I trial studies the side effects and the best dose of a vaccine therapy in treating patients with malignant peripheral nerve sheath tumor that cannot be removed by surgery (unresectable) or has come back after a period of improvement (recurrent). Vaccines made from a gene-modified virus may kill tumor cells expressing a gene called neurofibromin 1 (NF1) without affecting surrounding normal cells and may also help the body build an effective immune response to kill tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of intratumoral administration of an
      Edmonston strain measles virus genetically engineered to express neurofibromatosis type 1
      (NIS) (oncolytic measles virus encoding thyroidal sodium iodide symporter [MV-NIS]) in
      patients with inoperable or recurrent malignant peripheral nerve sheath tumor (MPNST).

      II. To determine the safety and toxicity of intratumoral administration of MV-NIS in patients
      with inoperable recurrent MPNST.

      III. To preliminarily assess antitumor efficacy of intratumoral MV-NIS administration by the
      rate of progression-free survival at 3 months, achieved by following radiographic response of
      the treated lesion using World Health Organization (WHO) response criteria guidelines.

      SECONDARY OBJECTIVES:

      I. To determine 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
      using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging.

      II. To assess viremia, viral replication, and measles virus shedding/persistence following
      intratumoral administration.

      III. To determine humoral and cellular immune response to the injected virus. IV. To assess
      the quality-of-life of patients treated with MV-NIS, using two inventories (Pain and
      Fatigue).

      V. To assess time to progression and differences in growth rates between treated and
      untreated tumor lesions.

      VI. To assess the overall survival time of patients treated with MV-NIS.

      OUTLINE:

      Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline
      and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and
      at 6 weeks based on whether there is uptake on prior imaging studies.

      After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (MV-NIS)ExperimentalPatients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies.
  • Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed MPNST, with or without underlying diagnosis of
             neurofibromatosis type 1 (diagnostic criteria for neurofibromatosis type 1)

          -  Measurable disease as defined by at least one tumor that is measurable in two
             dimensions on CT or magnetic resonance imaging (MRI) scan (minimum size 1.0 cm for at
             least one lesion)

          -  MPNST for which standard therapy is not curative, including patients with surgically
             unresectable lesions, progression (WHO criteria) or recurrence of an MPNST in a
             previously radiated field (if it has been at least 4 weeks prior to registration since
             the last dose of radiation); Note: patients with metastatic disease also are eligible
             for participation

          -  Patient may have more than one site of recurrent or metastatic disease but only one
             lesion that is >= 1 cm in size will be injected (if in the lung, the lesion must be >=
             2 cm and adjacent to the pleura in the lung)

          -  Absolute neutrophil count (ANC) >= 1500

          -  Platelet (PLT) >= 100,000

          -  Hemoglobin (HgB) >= 9.0 g/dL

          -  Total bilirubin =< institutional upper limit of normal (ULN)

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
             1.5 x upper limit of normal (ULN)

          -  Creatinine =< 1.0 mg/dL

          -  International normalized ratio (INR) =< 2.0

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Provide informed written consent

          -  Willingness to return to Mayo Clinic Rochester for follow-up

          -  Willingness to provide biologic samples for correlative research purposes

          -  Life expectancy >= 12 weeks

          -  Cluster of differentiation (CD)4 count >= 200/uL or >= 15% of peripheral blood
             lymphocytes

          -  Ability to complete questionnaire(s) by themselves or with assistance

        Exclusion Criteria:

          -  Any of the following

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception during treatment and 8 weeks following the completion of treatment

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Receiving therapeutic anticoagulation (Coumadin or low molecular weight heparin,
             heparin, apixaban, dabigatran, rivaroxaban, warfarin)

          -  Active infection =< 5 days prior to registration

          -  History of tuberculosis or history of purified protein derivative (PPD) positivity

          -  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

               -  Radiation therapy =< 3 weeks prior to registration

          -  Failure to fully recover from acute, reversible effects defined as =< grade 1 Common
             Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 of prior chemotherapy
             regardless of interval since last treatment except alopecia and neuropathy

          -  Requiring blood product support

          -  Patient has 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)

          -  Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled
             steroids

          -  Current exposure to household contacts =< 15 months old or household contact with
             known immunodeficiency; NOTE: patient must avoid contact during documented viral
             shedding; participants with continuous viral shedding will be given recommendations
             for restricted activities to avoid contact with immunocompromised persons

          -  Allergy to measles vaccine or history of severe reaction to prior measles vaccination

          -  Allergy to iodine; Note: this does not include reactions to intravenous contrast
             materials

          -  Allergy to lidocaine, fentanyl, midazolam, or propofol (may be used during tumor
             biopsy or injection)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best response using the World Health Organization response criteria
Time Frame:From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 2 years
Safety Issue:
Description:Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and dose level).

Secondary Outcome Measures

Measure:Absolute percentage change in quality of life measured using the Brief Pain Inventory (short form) and Brief Fatigue Inventory
Time Frame:Baseline to up to 2 years
Safety Issue:
Description:Determination of significant changes in quality of life over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. Quality of life will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in quality of life scores over time as well as associations between change in quality of life scores at different time points and per dose level.
Measure:Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography/computed tomography
Time Frame:Baseline to up to day 8
Safety Issue:
Description:Patients may be imaged on days 15, 28 and week 6. Absolute and percent change from baseline along with t-tests to evaluate change from baseline to all observed timepoints.
Measure:Growth-rate between treated and untreated lesions
Time Frame:Up to 2 years
Safety Issue:
Description:Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
Measure:Humoral and cellular immune response to the injected virus
Time Frame:Up to 2 years
Safety Issue:
Description: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).
Measure:Incidence of measles virus shedding/persistence following intratumoral administration
Time Frame:Up to 2 years
Safety Issue:
Description:Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Measure:Incidence of viral replication following intratumoral administration
Time Frame:Up to 2 years
Safety Issue:
Description:Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Measure:Incidence of viremia following intratumoral administration
Time Frame:Up to 2 years
Safety Issue:
Description:Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Measure:Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines
Time Frame:At 3 months
Safety Issue:
Description:A progression-free survival at 3 months success is defined as a patient who is alive and their treated lesion is progression free at three months after they have treatment with oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS).
Measure:Time to progression
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Viral gene expression
Time Frame:Up to 2 years
Safety Issue:
Description:Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
Measure:Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging
Time Frame:Up to day 8
Safety Issue:
Description:Patients may be imaged on days 15, 28 and week 6. Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Absolute and percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.

Details

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

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