Clinical Trial: VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: Phase I Trial of Intravenous Administration of Vesicular Stomatitis Virus Genetically Engineered to Express Thyroidal Sodium Iodide Symporter (NIS) and Human Interferon Beta (hIFNb) in Patients With M
Brief Summary: This phase I trial studies the side effects and best dose of vesicular stomatitis virus-human interferon beta-sodium iodide symporter (VSV-hIFNbeta-NIS) in treating patients with stage IV endometrial cancer or endometrial cancer that has come back. The study virus, VSV-hIFNbeta-NIS, has been changed so that it has restricted ability to spread to tumor cells and not to healthy cells. It also contains a gene for a protein, NIS, which helps the body concentrate iodine making it possible to track where the virus goes. VSV-hIFNbeta-NIS may be able to kill tumor cells without damaging normal cells.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To evaluate the optimal dose schedule, safety and tolerability as measured by the incidence of significant toxicity of VSV-hIFNbeta-NIS in immunocompetent patients with metastatic and/or recurrent endometrial cancer (EC).
SECONDARY OBJECTIVES:
I. To determine the toxicity profile of VSV-hIFNbeta-NIS. II. To determine the time course of viral gene expression and virus elimination, and the biodistribution of virally infected cells at various times points after infection with VSV-hIFNbeta-NIS using Tc-99m pertechnetate planar and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging.
III. To assess virus replication, viremia; viral shedding in urine and respiratory secretions; and virus persistence after intravenous (IV) administration of VSV-hIFNbeta-NIS.
IV. To monitor humoral responses to the injected virus. V. To estimate the tumor response rate and overall survival.
TERTIARY OBJECTIVES:
I. To determine the pharmacokinetic (PK) profile of VSV-IFNbeta-NIS in patients with EC by measurement of VSV-IFNbeta-NIS in blood by reverse transcriptase polymerase chain reaction (RT-PCR).
II. To characterize the pharmacodynamics (PD) of VSV-IFNbeta-NIS by way of measuring serum interferon-beta and also VSV-RT-PCR of VSV-IFNbeta-NIS listed above.
III. Assess CD8+ T cell (both general and VSV-IFNbeta-NIS specific) and natural killer (NK) cell responses.
IV. Gene expression analysis pre- and p
Sponsor: Mayo Clinic
Current Primary Outcome:
- Incidence of adverse events graded according to the NCI CTCAE version 4 [ Time Frame: Up to 1 year ]Frequency distributions and other descriptive measures will form the basis of the analysis of these variables. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals.
- Maximum tolerated dose of VSV-hIFNbeta-NIS graded according to the National Cancer Institute (NCI) CTCAE version 4 [ Time Frame: Up to 5 weeks ]Defined as the highest safely-tolerated dose level where at most one patient out of six experiences dose limiting toxicities (DLT) with the next higher dose level having at least 2 of 6 patients who have experienced DLT.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Biodistribution and kinetics of virus spread and NIS gene expression in vivo assessed via SPECT/CT [ Time Frame: Up to day 10 ]Will be correlated with tumor distribution.
- Number of clinical responses defined as complete response, partial response, or stable disease assessed by RECIST 1.1 criteria [ Time Frame: Up to 1 year ]Will be summarized by simple descriptive summary statistics across all patients in each group as well as by dose level and primary type of cancer (EC).
- Time until hematologic nadirs (white blood cells, ANC, platelets) [ Time Frame: Up to 1 year ]Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals. The effect of dose and ancillary dichotomized covariates such as age will be explored using logrank testing involving one covariate at a time.
- Time until treatment related grade 3+ toxicity graded according to the NCI CTCAE version 4 [ Time Frame: Up to 1 year ]Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and related confidence intervals. The effect of dose and ancillary dichotomized covariates such as age will be explored using logrank testing involving one covariate at a time.
- Viral replication and shedding in blood, throat washings, urine, and buccal swabs assessed via quantitative RT-PCR [ Time Frame: Up to 1 year ]Descriptive statistics and scatterplots will form the basis of presentation of these variables. Correlations with other outcome measures will be carried out by standard parametric and non-parametric tests (e.g. Pearson's and Spearman's rho).
Original Secondary Outcome: Same as current
Information By: Mayo Clinic
Dates:
Date Received: April 14, 2017
Date Started: June 15, 2017
Date Completion: June 2019
Last Updated: April 14, 2017
Last Verified: April 2017