Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
33

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1500/uL (obtained =< 14 days prior to registration)
Platelet count (PLT) >= 100,000/uL (obtained =< 14 days prior to registration)
Willingness to provide mandatory biological specimens for research purposes
...
Absolute neutrophil count (ANC) >= 1500/uL (obtained =< 14 days prior to registration)
Platelet count (PLT) >= 100,000/uL (obtained =< 14 days prior to registration)
Willingness to provide mandatory biological specimens for research purposes
Willingness to return to Mayo Clinic in Rochester, Minnesota for follow-up
Vaginal brachytherapy may have been administered at any time prior to registration
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
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
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)
Hemoglobin >= 10 g/dL (obtained =< 14 days prior to registration)
Total bilirubin =< 1.5 x ULN (obtained =< 14 days prior to registration)
NOTE: Group B patients have no maximum tumor size
Creatinine =< 2.0 mg/dL (obtained =< 14 days prior to registration)
Ability to provide written informed consent
NOTE: if baseline liver disease, Child Pugh score not exceeding class A
Life expectancy >= 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

Exclusion Criteria

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)
Known untreated or symptomatic brain metastases
Targeted biologic therapy < 4 weeks prior to registration
...
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)
Known untreated or symptomatic brain metastases
Targeted biologic therapy < 4 weeks prior to registration
Active central nervous system (CNS) disorder or seizure disorder or known CNS disease or neurologic symptomatology
Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids
Any immunotherapy-related adverse events Common Terminology Criteria for Adverse Events (CTCAE) > grade 1 at the time of registration
Chemotherapy < 4 weeks prior to registration
Active infection, including any active viral infection, =< 5 days prior to registration
Receipt of a live virus vaccine =< 2 months prior to registration
Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
Any viral or gene therapy prior to registration
Pregnant persons or persons of reproductive ability who are unwilling to use effective contraception
History of hepatitis B or C or chronic hepatitis
Immunotherapy < 4 weeks prior to registration
Any other pathology or condition that the principal investigator deems to negatively impact treatment safety
NOTE: Vaginal brachytherapy may be performed at any time prior to registration
Active or latent tuberculosis or hepatitis
Nursing persons
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])
Availability of and patient acceptance of curative therapy
Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression

Summary

Conditions
  • Recurrent Endometrial Endometrioid Adenocarcinoma
  • Metastatic Endometrial Carcinoma
  • Recurrent Endometrial Adenocarcinoma
  • Recurrent Endometrial Carcinoma
  • Recurrent Endometrial Clear Cell Adenocarcinoma
  • Recurrent Endometrial Mixed Cell Adenocarcinoma
  • Recurrent Endometrial Serous Adenocarcinoma
  • Recurrent Endometrial Undifferentiated Carcinoma
  • Recurrent Uterine Corpus Carcinosarcoma
  • Stage IV Uterine Corpus Cancer AJCC v7
  • Stage IVA Uterine Corpus Cancer AJCC v7
  • Stage IVB Uterine Corpus Cancer AJCC v7
Type
Interventional
Phase
Phase 1
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Only females

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 profi...

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.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1500/uL (obtained =< 14 days prior to registration)
Platelet count (PLT) >= 100,000/uL (obtained =< 14 days prior to registration)
Willingness to provide mandatory biological specimens for research purposes
...
Absolute neutrophil count (ANC) >= 1500/uL (obtained =< 14 days prior to registration)
Platelet count (PLT) >= 100,000/uL (obtained =< 14 days prior to registration)
Willingness to provide mandatory biological specimens for research purposes
Willingness to return to Mayo Clinic in Rochester, Minnesota for follow-up
Vaginal brachytherapy may have been administered at any time prior to registration
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
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
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)
Hemoglobin >= 10 g/dL (obtained =< 14 days prior to registration)
Total bilirubin =< 1.5 x ULN (obtained =< 14 days prior to registration)
NOTE: Group B patients have no maximum tumor size
Creatinine =< 2.0 mg/dL (obtained =< 14 days prior to registration)
Ability to provide written informed consent
NOTE: if baseline liver disease, Child Pugh score not exceeding class A
Life expectancy >= 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

Exclusion Criteria

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)
Known untreated or symptomatic brain metastases
Targeted biologic therapy < 4 weeks prior to registration
...
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)
Known untreated or symptomatic brain metastases
Targeted biologic therapy < 4 weeks prior to registration
Active central nervous system (CNS) disorder or seizure disorder or known CNS disease or neurologic symptomatology
Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids
Any immunotherapy-related adverse events Common Terminology Criteria for Adverse Events (CTCAE) > grade 1 at the time of registration
Chemotherapy < 4 weeks prior to registration
Active infection, including any active viral infection, =< 5 days prior to registration
Receipt of a live virus vaccine =< 2 months prior to registration
Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
Any viral or gene therapy prior to registration
Pregnant persons or persons of reproductive ability who are unwilling to use effective contraception
History of hepatitis B or C or chronic hepatitis
Immunotherapy < 4 weeks prior to registration
Any other pathology or condition that the principal investigator deems to negatively impact treatment safety
NOTE: Vaginal brachytherapy may be performed at any time prior to registration
Active or latent tuberculosis or hepatitis
Nursing persons
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])
Availability of and patient acceptance of curative therapy
Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression

Locations

Rochester, Minnesota, 55905
Rochester, Minnesota, 55905

Tracking Information

NCT #
NCT03120624
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Jamie N Bakkum-Gamez Mayo Clinic in Rochester
  • Jamie N Bakkum-Gamez Mayo Clinic in Rochester