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

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

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 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 s
Sponsor: Mayo Clinic

Current Primary Outcome:

• 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 ]
  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).
• Incidence of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years after treatment ]
  The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
• Maximum tolerated dose defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT [ Time Frame: 6 weeks ]
  Assessed according to according to Common Terminology Criteria for Adverse Events version 4.0. The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.

Original Primary Outcome:

• Best response using the WHO 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 ]
  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).
• Incidence of adverse events according to the National Cancer Institute CTCAE v. 4.0 [ Time Frame: Up to 2 years after treatment ]
  The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
• MTD defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT according to CTCAE v. 4.0 [ Time Frame: 6 weeks ]
  The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.

Current Secondary Outcome:

• 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 ]
  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.
• 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 ]
  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.
• Growth-rate between treated and untreated lesions [ Time Frame: Up to 2 years ]
  Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
• Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
  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 measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
  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.
• Incidence of viral replication following intratumoral administration [ Time Frame: Up to 2 years ]
  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.
• Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
  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.
• Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines [ Time Frame: At 3 months ]
  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).
• Time to progression [ Time Frame: Up to 2 years ]
• Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin) [ Time Frame: Up to 2 years ]
• Viral gene expression [ Time Frame: Up to 2 years ]
  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.
• Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging [ Time Frame: Up to day 8 ]
  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.

Original Secondary Outcome:

• Absolute percentage change in quality of life (QOL) measured using the Brief Pain Inventory (short form) [ Time Frame: Baseline to up to 2 years ]
  Determination of significant changes in QOL over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. QOL will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in QOL scores over time as well as associations between change in QOL scores at different time points and per dose level.
• Absolute percentage change in quality of life (QOL) measured using the Brief Fatigue Inventory [ Time Frame: Baseline to up to 2 years ]
  Determination of significant changes in QOL over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. QOL will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in QOL scores over time as well as associations between change in QOL scores at different time points and per dose level.
• Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using SPECT/CT [ Time Frame: Baseline to up to week 6 ]
  Patients may be imaged on days 15, 28 and week 6. Absolute change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
• Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using SPECT/CT [ Time Frame: Baseline to up to week 6 ]
  Patients may be imaged on days 15, 28 and week 6. Percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
• Growth-rate between treated and untreated lesions [ Time Frame: Up to 2 years ]
  Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
• Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
  Correlations between these laboratory values and response will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
• Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
  Correlations between these laboratory values and dose levels will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
• Incidence of measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
  Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and response will be carried out in an exploratory manner.
• Incidence of measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
  Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and dose levels will be carried out in an exploratory manner.
• Incidence of viral replication following intratumoral administration [ Time Frame: Up to 2 years ]
  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.
• Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
  Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and response will be carried out in an exploratory manner.
• Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
  Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and dose levels will be carried out in an exploratory manner.
• Progression-free survival (PFS) by radiographic response of the treated lesion using WHO response criteria guidelines [ Time Frame: At 3 months ]
  A PFS3 success is defined as a patient who is alive and their treated lesion is progression free at three months after they have treatment with MV-NIS.
• Time to progression [ Time Frame: Up to 2 years ]
• Time until hematologic nadirs (ANC) [ Time Frame: Up to 2 years ]
  Information By: Mayo Clinic
  

  Dates:
  Date Received: February 25, 2016
  Date Started: June 2017
  Date Completion: June 2021
  Last Updated: May 17, 2017
  Last Verified: December 2016