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

  • STATUS
    Recruiting
  • End date
    Jul 15, 2023
  • participants needed
    77
  • sponsor
    Mayo Clinic
Updated on 5 August 2021
ct scan
platelet count
measurable disease
carcinoma
warfarin
neutrophil count
hormone therapy
tumor cells
primary tumor
chemotherapy regimen
adenocarcinoma
undifferentiated carcinoma
endometrial carcinoma
carcinosarcoma
serous adenocarcinoma
vesicular stomatitis
sodium-iodide symporter

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) 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.

Description

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 Tc-99m pertechnetate planar and single photon emission computed tomography (SPECT)/computed tomography (CT) or 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: 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, undergo whole body planar imaging and SPECT/CT imaging or 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 undergo another planar and SPECT/CT imaging or 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. 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, undergo whole body planar imaging and SPECT/CT imaging or 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 undergo another planar and SPECT/CT imaging or 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. 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 at day 29, every 3 months until disease progression and then every 6 months for up to 5 years.

Details
Condition Endometrial Clear Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Recurrent Uterine Corpus Carcinoma, Ovarian Endometrioid Adenocarcinoma, Stage IVA Uterine Corpus Cancer, Recurrent Endometrial Cancer, Stage IVB Uterine Corpus Cancer, Endometrial Undifferentiated Carcinoma, Stage IV Uterine Corpus Cancer, Stage IV Uterine Corpus Cancer AJCC v7, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7, Endometrial Mixed Adenocarcinoma, Metastatic Endometrioid Adenocarcinoma, Recurrent Endometrial Serous Adenocarcinoma, Recurrent Endometrial Carcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Adenocarcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Mixed Cell Adenocarcinoma, Recurrent Endometrial Undifferentiated Carcinoma, Metastatic Endometrial Carcinoma, Recurrent Uterine Corpus Carcinosarcoma, endometrial adenocarcinoma recurrent
Treatment laboratory biomarker analysis, biopsy, computed tomography, positron emission tomography, Ruxolitinib, pharmacological study, single photon emission computed tomography, Ruxolitinib Phosphate, Planar Imaging, Technetium Tc-99m Sodium Pertechnetate, VSV-hIFNbeta-NIS, Fluorine F 18 Tetrafluoroborate, Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter
Clinical Study IdentifierNCT03120624
SponsorMayo Clinic
Last Modified on5 August 2021

Eligibility

Yes No Not Sure

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, 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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note