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VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

This study is currently recruiting participants.
Verified April 2017 by Mayo Clinic
Sponsor:
ClinicalTrials.gov Identifier:
NCT03120624
First Posted: April 19, 2017
Last Update Posted: September 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
  Purpose
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.

Condition Intervention Phase
Endometrial Clear Cell Adenocarcinoma Endometrial Mixed Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Recurrent Endometrial Serous Adenocarcinoma Recurrent Uterine Corpus Carcinoma Stage IV Uterine Corpus Cancer Stage IVA Uterine Corpus Cancer Stage IVB Uterine Corpus Cancer Procedure: Biopsy Procedure: Computed Tomography Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Planar Imaging Procedure: Single Photon Emission Computed Tomography Drug: Technetium Tc-99m Sodium Pertechnetate Biological: VSV-hIFNbeta-NIS Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Metastatic or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 33
Actual Study Start Date: September 15, 2017
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (VSV-hIFNbeta-NIS, SPECT/CT, biopsy)
Patients receive VSV-hIFNbeta-NIS IV over 30-60 minutes on day 1. After 3-5 days, patients receive technetium Tc-99m sodium pertechnetate IV, and about 30 minutes later, undergo whole body planar imaging and SPECT/CT imaging. If previous imaging data are positive, patients receive technetium Tc-99m sodium pertechnetate IV and undergo another planar and SPECT/CT scan 7-10 days after VSV-hIFNbeta-NIS infusion. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Patients also undergo image-guided biopsy of accessible tumor on day 29.
Procedure: Biopsy
Undergo image-guided biopsy
Other Name: Bx
Procedure: Computed Tomography
Undergo SPECT/CT
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT SCAN
  • tomography
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Procedure: Planar Imaging
Undergo whole body planar imaging
Procedure: Single Photon Emission Computed Tomography
Undergo SPECT/CT
Other Names:
  • Medical Imaging, Single Photon Emission Computed Tomography
  • Single Photon Emission Tomography
  • single-photon emission computed tomography
  • SPECT
  • SPECT imaging
  • SPECT SCAN
  • SPET
  • tomography, emission computed, single photon
  • Tomography, Emission-Computed, Single-Photon
Drug: Technetium Tc-99m Sodium Pertechnetate
Given IV
Other Names:
  • Pertscan-99m
  • Sodium Pertechnetate (Na99mtco4)
  • Tc 99m Generator
  • Ultra-Technekow FM
Biological: VSV-hIFNbeta-NIS
Given IV
Other Names:
  • Oncolytic VSV-hIFNbeta-NIS
  • Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter
  • VSV-expressing hIFNb and NIS
  • VSV-hIFNb-NIS

Detailed Description:

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 post-virotherapy. V. Evaluate transcription of interferon mediated genes (protein kinase R, the death receptor-TRAIL, 2'-5' oligoadenylate/RNAse L proteins, heat shock proteins [Hsp 60/70/90], major histocompatibility class antigens and IRF-7).

VI. Assess presence of VSV in tumor and normal tissues subsequent to administration of IV VSV-IFNbeta-NIS.

OUTLINE: This is a dose-escalation study of VSV-hIFNbeta-NIS.

Patients receive VSV-hIFNbeta-NIS IV over 30-60 minutes on day 1. After 3-5 days, patients receive technetium Tc-99m sodium pertechnetate IV, and about 30 minutes later, undergo whole body planar imaging and SPECT/CT imaging. If previous imaging data are positive, patients receive technetium Tc-99m sodium pertechnetate IV and undergo another planar and SPECT/CT scan 7-10 days after VSV-hIFNbeta-NIS infusion. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Patients also undergo image-guided biopsy of accessible tumor on day 29.

After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma; largest tumor diameter =< 5cm

    • NOTE: Histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (NOS)
    • NOTE: Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet count (PLT) >= 100,000/uL
  • Hemoglobin >= 10 g/dL
  • Creatinine =< 2.0 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit of normal (ULN)

    • NOTE: If baseline liver disease, Child Pugh score not exceeding class A
  • Total bilirubin =< 1.5 x ULN
  • International normalized ratio (INR)/prothrombin time (PT), activated partial thromboplastin time (aPTT) =< 1.4 x ULN unless on therapeutic warfarin then INR/PT =< 3.5
  • Ability to provide written informed consent
  • Willingness to return to Mayo Clinic in Rochester, Minnesota for follow-up
  • Life expectancy >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Willingness to provide mandatory biological specimens for research purposes
  • Prior therapy:

    • Any number of prior chemotherapy regimens and/or targeted therapies and/or prior external beam radiation therapy and/or prior hormonal therapy for endometrial cancer are allowed provided the last treatment was > 4 weeks prior to registration
    • Vaginal brachytherapy may have been administered at any time prior to registration

Exclusion Criteria:

  • Availability of and patient acceptance of curative therapy
  • Active infection, including any active viral infection, =< 5 days prior to registration
  • Active or latent tuberculosis or hepatitis
  • Known untreated or symptomatic brain metastases
  • Any of the following prior therapies:

    • Chemotherapy =< 4 weeks prior to registration
    • Targeted biologic therapy =< 4 weeks prior to registration
    • Immunotherapy =< 4 weeks prior to registration
    • Any viral or gene therapy prior to registration
    • External beam radiotherapy =< 4 weeks prior to registration

      • NOTE: Vaginal brachytherapy may be performed at any time prior to registration
  • New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or uncontrolled current cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia [SVT])
  • Active central nervous system (CNS) disorder or seizure disorder or known CNS disease or neurologic symptomatology
  • Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression
  • History of hepatitis B or C or chronic hepatitis
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used 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
  • Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
  • Any of the following:

    • Pregnant persons or persons of reproductive ability who are unwilling to use effective contraception
    • Nursing persons
  • Any other pathology or condition that the principal investigator deems to negatively impact treatment safety
  • Any immunotherapy-related adverse events Common Terminology Criteria for Adverse Events (CTCAE) > grade 1 at the time of registration
  • Receipt of a live virus vaccine =< 2 months prior to registration
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03120624


Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Jamie N. Bakkum-Gamez         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jamie Bakkum-Gamez Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT03120624     History of Changes
Other Study ID Numbers: MC1562
NCI-2017-00615 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1562 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: April 14, 2017
First Posted: April 19, 2017
Last Update Posted: September 20, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Endometrial Neoplasms
Uterine Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Adenocarcinoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Ovarian Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Interferons
Interferon-beta
Sodium Pertechnetate Tc 99m
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs