VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Stage IV or Recurrent Endometrial Cancer
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| ClinicalTrials.gov Identifier: NCT03120624 |
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Recruitment Status :
Recruiting
First Posted : April 19, 2017
Last Update Posted : July 18, 2022
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Sponsor:
Mayo Clinic
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
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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) 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Endometrial Carcinoma Recurrent Endometrial Adenocarcinoma Recurrent Endometrial Carcinoma Recurrent Endometrial Clear Cell Adenocarcinoma Recurrent Endometrial Endometrioid 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 | Procedure: Biopsy Procedure: Computed Tomography Other: Fluorine F 18 Tetrafluoroborate Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Planar Imaging Procedure: Positron Emission Tomography Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter Drug: Ruxolitinib Drug: Ruxolitinib Phosphate Procedure: Single Photon Emission Computed Tomography Drug: Technetium Tc-99m Sodium Pertechnetate | Phase 1 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 77 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel 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 |
| Actual Study Start Date : | September 15, 2017 |
| Estimated Primary Completion Date : | June 1, 2023 |
| Estimated Study Completion Date : | July 15, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (VSV-hIFNbeta-NIS, SPECT/CT, TFB-PET, biopsy)
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.
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Procedure: Biopsy
Undergo image-guided biopsy
Other Names:
Procedure: Computed Tomography Undergo SPECT/CT
Other Names:
Other: Fluorine F 18 Tetrafluoroborate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Procedure: Planar Imaging Undergo whole body planar imaging Procedure: Positron Emission Tomography Undergo TFB-PET
Other Names:
Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter Given IV
Other Names:
Procedure: Single Photon Emission Computed Tomography Undergo SPECT/CT
Other Names:
Drug: Technetium Tc-99m Sodium Pertechnetate Given IV
Other Names:
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Experimental: Arm B (ruxolitinib, VSV-hIFNbeta-NIS, SPECT/CT,TFB-PET,biopsy)
Patients receive ruxolitinib phosphate PO 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.
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Procedure: Biopsy
Undergo image-guided biopsy
Other Names:
Procedure: Computed Tomography Undergo SPECT/CT
Other Names:
Other: Fluorine F 18 Tetrafluoroborate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Procedure: Planar Imaging Undergo whole body planar imaging Procedure: Positron Emission Tomography Undergo TFB-PET
Other Names:
Biological: Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter Given IV
Other Names:
Drug: Ruxolitinib Given PO
Other Names:
Drug: Ruxolitinib Phosphate Given PO
Other Names:
Procedure: Single Photon Emission Computed Tomography Undergo SPECT/CT
Other Names:
Drug: Technetium Tc-99m Sodium Pertechnetate Given IV
Other Names:
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Primary Outcome Measures :
- Maximum tolerated dose of VSV-hIFNbeta-NIS (alone and in combination with ruxolitinib phosphate) [ Time Frame: Up to 28 days ]Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. 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.
- Incidence of adverse events [ Time Frame: Up to 1 year ]Graded according to the NCI CTCAE version 4. 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.
Secondary Outcome Measures :
- Number of clinical responses [ Time Frame: Up to 1 year ]Defined as complete response, partial response, or stable disease assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. 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).
- Viral replication and shedding in blood, throat washings, urine, and buccal swabs assessed via quantitative reverse transcriptase polymerase chain reaction [ 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).
- Biodistribution and kinetics of virus spread and NIS gene expression in vivo [ Time Frame: Up to day 10 ]Assessed via single-photon emission computed tomography/computed tomography. Will be correlated with tumor distribution.
- Time until treatment related grade 3+ toxicity [ Time Frame: Up to 1 year ]Graded according to the NCI CTCAE version 4. 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 hematologic nadirs (white blood cells, absolute neutrophil count, 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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)
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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)
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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
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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
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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
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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
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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
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 in Rochester | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu | |
| Principal Investigator: Jamie N. Bakkum-Gamez, M.D. | |
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Jamie N Bakkum-Gamez | Mayo Clinic in Rochester |
| Responsible Party: | Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT03120624 |
| Other Study ID Numbers: |
MC1562 NCI-2017-00615 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MC1562 ( Other Identifier: Mayo Clinic in Rochester ) P30CA015083 ( U.S. NIH Grant/Contract ) |
| First Posted: | April 19, 2017 Key Record Dates |
| Last Update Posted: | July 18, 2022 |
| Last Verified: | July 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Adenocarcinoma Endometrial Neoplasms Cystadenocarcinoma, Serous Carcinoma, Endometrioid Carcinosarcoma Adenocarcinoma, Clear Cell Recurrence Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Disease Attributes Pathologic Processes Uterine Neoplasms Genital Neoplasms, Female |
Urogenital Neoplasms Neoplasms by Site Uterine Diseases Cystadenocarcinoma Neoplasms, Cystic, Mucinous, and Serous Ovarian Neoplasms Ovarian Diseases Adnexal Diseases Gonadal Disorders Endocrine System Diseases Neoplasms, Complex and Mixed Sarcoma Neoplasms, Connective and Soft Tissue Iodine Interferons |