Modified Virus Therapy +/− Ruxolitinib for Endometrial Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Corticosteroids, others

Disqualifiers: Active infection, Brain metastases, Cardiac disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new virus therapy, VSV-hIFNbeta-NIS, which might target and kill tumor cells in endometrial cancer without harming healthy cells. Researchers aim to assess the virus's effectiveness when used alone or with ruxolitinib (also known as Jakafi, Jakavi, Opzelura, INCB018424, or INC424), a drug that could block cancer cell growth. People with stage IV or recurrent endometrial cancer who have undergone chemotherapy or other treatments but still have cancer may qualify for this study. As a Phase 1 trial, this research seeks to understand how this new treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the study virus, VSV-hIFNbeta-NIS, targets cancer cells without harming healthy ones. Various studies have tested it, and results indicate that it is generally safe and well-tolerated by patients. The virus is engineered to focus specifically on cancer cells and includes a gene that helps track its location in the body, enhancing precision.

For ruxolitinib phosphate, research suggests it can inhibit cancer cell growth by blocking certain necessary enzymes. Its approval for other conditions provides some confidence in its safety.

Together, these treatments aim to improve outcomes for patients with endometrial cancer. The current study is in its early stages, focusing on understanding side effects and determining the best dose. This phase is crucial for gathering safety data, but it also means there is limited information on how patients will respond to these treatments when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the VSV-hIFNbeta-NIS treatment for endometrial cancer because it utilizes a modified virus to deliver an active ingredient directly into cancer cells, which is a novel approach compared to traditional chemotherapy or hormone therapy. This treatment leverages a virus engineered to produce interferon-beta, a protein that can enhance the immune response against cancer, potentially leading to more targeted destruction of tumor cells. Additionally, it incorporates a unique imaging agent, NIS, allowing for precise tracking of the treatment's effect on tumors through advanced imaging techniques like TFB-PET. This dual-action approach of targeting cancer cells while also enabling real-time monitoring sets it apart from existing therapies and offers a promising new avenue for treatment.

What evidence suggests that this trial's treatments could be effective for endometrial cancer?

Research has shown that VSV-hIFNbeta-NIS, a modified virus, may effectively target cancer cells while sparing healthy ones. In animal studies, this virus treatment successfully controlled and even shrank tumors. In this trial, some participants will receive VSV-hIFNbeta-NIS alone, while others will receive it in combination with ruxolitinib phosphate. Ruxolitinib blocks enzymes that aid tumor growth. Together, these treatments could prove more effective than the virus alone. Early evidence suggests this combination could be a strong option for treating endometrial cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Jamie N. Bakkum-Gamez, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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.

You are expected to live at least 12 more weeks.

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12490404/

Long-term safety and effectiveness of ruxolitinib in patients ... After 6 months of ruxolitinib treatment, 26.2% of patients had a spleen response and 52.0% of patients had less symptoms. We could not calculate ...

2. ajmc.com ajmc.com/view/ash-2024-showcases-real-world-data-demonstrating-efficacy-of-ruxolitinib-across-multiple-conditions

ASH 2024 Showcases Real-World Data Demonstrating ... Ruxolitinib improved hematocrit and white blood cell levels in PV patients, showing superiority over hydroxyurea and reducing phlebotomy frequency. In cGVHD ...

3. targetedonc.com targetedonc.com/view/long-term-reach3-data-confirm-ruxolitinib-s-efficacy-in-steroid-refractory-cgvhd

Long-Term REACH3 Data Confirm Ruxolitinib's Efficacy in ... Ruxolitinib shows sustained efficacy and safety in treating steroid-refractory chronic graft-vs-host disease, outperforming standard therapies over three years.

4. ctv.veeva.com ctv.veeva.com/study/vsv-hifnbeta-nis-with-or-without-ruxolitinib-phosphate-in-treating-patients-with-stage-iv-or-recurre

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in ... Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving VSV-hIFNbeta-NIS with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8900057/

Real-World Outcomes of Ruxolitinib Treatment for ... Ruxolitinib has been demonstrated to have clinical efficacy in patients with PV with regards to hematocrit control, splenomegaly, and symptom management. The ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03120624

Study Details | NCT03120624 | VSV-hIFNbeta-NIS With or ... Giving VSV-hIFNbeta-NIS with ruxolitinib phosphate may work better in treating patients with endometrial cancer compared to VSV-hIFNbeta-NIS alone. PRIMARY ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9445918/

Uterine Serous Carcinoma - PMC Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. ... VSV-hIFNbeta-NIS, with/without Ruxolitinib, Phase I, Oncolytic ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24004468

Uterine serous carcinoma: key advances and novel ... VSV-hIFNbeta-NIS with or without ruxolitinib phosphate in treating patients with stage IV or recurrent endometrial cancer clinicalTrials.gov: NCI. Available ...

9. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/recurrent-cancer

Recurrent Cancer Clinical Trials 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 ...

10. delta.larvol.com delta.larvol.com/Products/?ProductId=2cf2fa96-f3c3-460e-98b0-3008b2c75b81

Voyager-V1 / Vyriad Delicious. August 02, 2024. VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer ... VSV-hIFNbeta-NIS ...