VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer

This phase I trial studies the side effects and best dose of vesicular stomatitis virus-human interferon beta-sodium iodide symporter (VSV-hIFNbeta-NIS) with or without ruxolitinib phosphate 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. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving VSV-hIFNbeta-NIS with ruxolitinib phosphate may work better in treating patients with endometrial cancer compared to VSV-hIFNbeta-NIS alone.

PRIMARY OBJECTIVE:

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 (alone and in combination with ruxolitinib phosphate \[ruxolitinib\]).

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 (alone and in combination with ruxolitinib) using fluorine F18 tetrafluoroborate (TFB)-positron emission tomography (PET) 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 (alone and in combination with ruxolitinib).

IV. To monitor humoral responses to the injected virus. V. To estimate the tumor response rate and overall survival.

CORRELATIVE 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 are randomized to 1 of 2 arms.

ARM A (EFFECTIVE AS OF 1/10/2023, GROUP A IS PERMANENTLY CLOSED TO ACCRUAL): Patients receive VSV-hIFNbeta-NIS IV over 60-90 minutes on day 1. After 2 days, patients receive technetium Tc-99m sodium pertechnetate IV, and about 30 minutes later, receive fluorine F18 tetrafluoroborate IV and undergo TFB-PET imaging. If previous imaging data are positive, patients receive technetium Tc-99m sodium pertechnetate IV, fluorine F18 tetrafluoroborate IV and undergo another TFB-PET imaging between 7-10 days and on 15 days if needed after VSV-hIFNbeta-NIS infusion. Patients also undergo computed tomography (CT) throughout the study. Patients also undergo mouth rinse, buccal swab and urine on study and blood sample collection throughout the study. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Patients also undergo image-guided biopsy of accessible tumor on day 29.

ARM B: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days -3 to 9. Patients also receive VSV-hIFNbeta-NIS IV over 60-90 minutes on day 1. After 2 days, patients receive technetium Tc-99m sodium pertechnetate IV, and about 30 minutes later, receive fluorine F18 tetrafluoroborate IV and undergo TFB-PET imaging. If previous imaging data are positive, patients receive technetium Tc-99m sodium pertechnetate IV and fluorine F18 tetrafluoroborate IV and undergo another TFB-PET imaging between 7-10 days and on 15 days if needed after VSV-hIFNbeta-NIS infusion. Patients also undergo CT throughout the study. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Patients also undergo image-guided biopsy of accessible tumor on day 29. Patients also undergo mouth rinse, buccal swab and urine on study and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at day 29, every 3 months until disease progression and then every 6 months for up to 5 years.

Eligibility Criteria:
Inclusion Criteria:

* Measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma

  * 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, carcinosarcoma, adenocarcinoma not otherwise specified (NOS)
  * NOTE: measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)
* Group A only: Largest tumor diameter =\< 5 cm

  * NOTE: Group B patients have no maximum tumor size
* Absolute neutrophil count (ANC) \>= 1500/uL (obtained =\< 14 days prior to registration)
* Platelet count (PLT) \>= 100,000/uL (obtained =\< 14 days prior to registration)
* Hemoglobin \>= 10 g/dL (obtained =\< 14 days prior to registration)
* Creatinine =\< 2.0 mg/dL (obtained =\< 14 days prior to registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)

  * NOTE: if baseline liver disease, Child Pugh score not exceeding class A
* Total bilirubin =\< 1.5 x ULN (obtained =\< 14 days prior to registration)
* International normalized ratio (INR)/prothrombin time (PT), activated partial thromboplastin time (aPTT) =\< 1.4 x ULN (obtained =\< 14 days prior to registration) 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 requiring treatment, 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 because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

  * 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