Modified Virus Therapy +/− Ruxolitinib for Endometrial Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Mayo Clinic

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

34 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot have had chemotherapy, targeted biologic therapy, or immunotherapy within 4 weeks before joining the trial. It's best to discuss your specific medications with the trial team.

Is the combination of modified virus therapy and ruxolitinib safe for humans?

Ruxolitinib has been shown to be generally well-tolerated in various studies, with common side effects including anemia (low red blood cell count) and thrombocytopenia (low platelet count), which are manageable. In combination with oncolytic virus therapy, it has been used in animal models without causing significant additional toxicity, suggesting it may be safe for human use. ^{1 2 3 4 5}

How is the treatment VSV-hIFNbeta-NIS with or without ruxolitinib different from other treatments for endometrial cancer?

This treatment is unique because it uses a modified virus (VSV) that selectively targets cancer cells while sparing normal cells, and it can be combined with ruxolitinib, a drug that blocks a specific cell signaling pathway (JAK/STAT) to enhance the virus's effectiveness. This approach is different from traditional treatments as it leverages the body's immune response and viral therapy to attack cancer cells. ^{1 3 6 7 8}

Research Team

Jamie N. Bakkum-Gamez, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with advanced or recurrent endometrial cancer. Participants must have a life expectancy of at least 12 weeks, be able to consent and return for follow-up, and meet specific health criteria like proper kidney function and blood counts. It's not open to those who are pregnant, nursing, have active infections or certain heart conditions, or those who've had recent chemotherapy or other treatments that might interfere.

Inclusion Criteria

Your platelet count is at least 100,000 per microliter within the past 14 days.

Your AST and ALT levels are not more than twice the upper limit of normal.

You are expected to live at least 12 more weeks.

Exclusion Criteria

I have not had external beam radiotherapy in the last 4 weeks.

I have brain metastases that are either untreated or causing symptoms.

I have not had immunotherapy in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive VSV-hIFNbeta-NIS IV and undergo various imaging and biopsy procedures. Arm B includes additional treatment with ruxolitinib phosphate.

4 weeks

Multiple visits for imaging and biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at day 29, every 3 months until disease progression, and then every 6 months for up to 5 years.

Up to 5 years

Regular follow-up visits

Treatment Details

Interventions

• Ruxolitinib Phosphate
• VSV-hIFNbeta-NIS

Trial Overview The study tests VSV-hIFNbeta-NIS alone or combined with ruxolitinib phosphate in stage IV/endometrial cancer patients. The virus targets tumor cells without harming healthy ones and includes a gene helping track the virus in the body. Ruxolitinib may halt tumor growth by blocking enzymes needed for cell growth.

Participant Groups

Group I: Arm B (ruxolitinib, VSV-hIFNbeta-NIS, SPECT/CT,TFB-PET,biopsy) Experimental Treatment 9 Interventions

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, 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 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. 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.

Group II: Arm A (VSV-hIFNbeta-NIS, TFB-PET, biopsy) Experimental Treatment 8 Interventions

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 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. Biopsy of accessible NIS image-positive tumors may occur after any imaging. Patients also undergo 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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, was found to be well-tolerated in a phase 1 trial involving 49 children with recurrent solid tumors and hematologic malignancies, with a recommended phase 2 dose of 50 mg/m² per dose.

While no objective responses were observed in patients with solid tumors, one patient with polycythemia vera achieved a partial response, indicating potential efficacy in specific hematologic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 dosing study of ruxolitinib in children with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms: A Children's Oncology Group phase 1 consortium study (ADVL1011). Loh, ML., Tasian, SK., Rabin, KR., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, effectively inhibits STAT3 activation and reduces ovarian tumor growth in both cancer cells and mouse models, suggesting its potential as a treatment for ovarian cancer.

When combined with the chemotherapy agent paclitaxel, ruxolitinib significantly enhances anti-tumor activity, leading to greater tumor reduction compared to using either treatment alone, indicating a promising strategy for advanced and chemoresistant ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. Han, ES., Wen, W., Dellinger, TH., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Application of interferon modulators to overcome partial resistance of human ovarian cancers to VSV-GP oncolytic viral therapy. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A phase 1 dosing study of ruxolitinib in children with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms: A Children's Oncology Group phase 1 consortium study (ADVL1011). [2021]

6. China pubmed.ncbi.nlm.nih.gov

[The Effect of Ruxolitinib on the Expression of VEGF and HIF-1α in Leukemia HEL Cells]. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. [2021]