Ruxolitinib for Skin Cancer

No longer recruiting at 2 trial locations

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: Strong CYP3A4 drugs

Disqualifiers: Brain metastases, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ruxolitinib, a pill targeting proteins linked to advanced skin cancer, specifically in organ transplant recipients. It aims to evaluate the treatment's effectiveness for those with cutaneous squamous cell carcinoma that has spread. The study begins by assessing the treatment's safety at various doses. Individuals who have undergone a solid organ transplant, require ongoing immune-suppressing medication, and have this specific advanced skin cancer may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications before starting the study drug. Specifically, you must stop any systemic chemotherapy or immunotherapy at least 21 days before, and any radiation therapy at least 14 days before. Additionally, you cannot use strong CYP3A4 drugs within 14 days or 5 drug half-lives before starting the study drug.

Is there any evidence suggesting that ruxolitinib is likely to be safe for humans?

Research has shown that ruxolitinib is generally well-tolerated by patients. Earlier studies found that people using ruxolitinib cream did not experience major body-wide side effects, suggesting the treatment is relatively safe.

However, some studies have found that patients taking oral JAK inhibitors, such as ruxolitinib, might face a slightly higher risk of developing other types of cancers, besides non-melanoma skin cancer. These risks have been observed in broader treatment settings.

Overall, while some risks exist, the treatment has been used in other situations with a reasonable safety record. Clinical trial participants are closely monitored to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, which often involve surgery, radiation, or chemotherapy, ruxolitinib is unique because it targets the Janus kinase (JAK) pathway, a key player in the inflammatory process involved in cancer cell growth. This targeted approach means it could potentially slow down or stop cancer cell proliferation more precisely than traditional methods. Researchers are excited about ruxolitinib because it offers a novel mechanism of action that might result in fewer side effects and improved patient outcomes compared to conventional treatments.

What evidence suggests that ruxolitinib might be an effective treatment for skin cancer?

Research has shown that ruxolitinib, a drug that blocks certain proteins, may help treat some skin conditions. It has proven effective for atopic dermatitis, leading to much clearer skin. However, some studies found a higher risk of nonmelanoma skin cancers in people using ruxolitinib for other conditions, so careful monitoring is important. While direct evidence for its use in treating advanced cutaneous squamous cell carcinoma (cSCC) is limited, its mechanism suggests it could help by targeting cancer cell growth. This trial will investigate its potential to treat cSCC in people who have had organ transplants. ^{2 5 6 7 8}

Who Is on the Research Team?

Alexander Wei, MD

Principal Investigator

Associate Professor of Medicine at the Columbia University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced skin cancer (cSCC) after a solid organ transplant. They must have measurable disease, be in fair health (KPS ≥60%, ECOG ≤2), and have recovered from previous treatments. A biopsy may be required, they can't be pregnant, must take oral meds well, haven't used JAK inhibitors before, and their organs must work properly.

Inclusion Criteria

Negative pregnancy test for women of child bearing potential

I have had an organ transplant and am on immunosuppressants.

I can take pills by mouth.

Exclusion Criteria

I have been treated with a JAK inhibitor before.

I am not HIV-positive or on antiretroviral therapy.

I haven't had major surgery in the last 4 weeks, except for procedures to place a vascular access device.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

In a safety lead-in of 6 patients, subjects will receive 15mg of ruxolitinib twice daily (BID) for 4 weeks to assess dose-limiting toxicities.

4 weeks

2 visits (in-person) on Day 1 and Day 15

Treatment

Participants receive ruxolitinib 15mg BID in a Simon two-stage design, with regular safety assessments.

24 weeks

1 visit (in-person) every cycle starting from cycle 3

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival.

Up to 17 months

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests Ruxolitinib's effectiveness on cSCC in transplant recipients. Initially, patients get 15mg twice daily; if side effects are manageable, the dose continues or reduces to 10mg based on early results. It's an open-label Phase II trial using Simon two-stage design to adjust dosing.

How Is the Trial Designed?

Group I: Ruxolitinib Experimental Treatment 1 Intervention

In a safety lead-in of 6 patients, subjects will receive 15mg of ruxolitinib twice daily (BID). After 4 weeks, if dose-limiting toxicities (DLT) are observed in 1 or fewer patients, the study will enter stage 1 of the Simon two-stage design where all subsequent patients will receive a starting dose of ruxolitinib 15mg BID. Subjects will have regularly scheduled study visits at the clinical site on Day 1 and Day 15 (± 3 days) of the first 2 cycles, then on Day 1 (± 3 days) of every subsequent cycle (starting cycle 3), where safety assessments, including laboratory assessments, vital signs, and physical examinations will be performed.

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Citations

1. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-new-data-phase-3b-true-ad4-trial-opzelurar

Incyte Announces New Data from Phase 3b TRuE-AD4 ... Patients treated with Opzelura demonstrated improvement in EASI75 (43.8% vs. 3.7%, nominal P<0.0001) and IGA-TS (29.4% vs. 2.5%, nominal P< ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34648874/

A 10-year retrospective cohort study of ruxolitinib and ... Our real-world results indicate that SCC risk is increased in patients with PV or MF taking ruxolitinib and support consideration of skin cancer monitoring.

3. ashpublications.org ashpublications.org/blood/article/143/2/178/498713/Outcomes-and-characteristics-of-nonmelanoma-skin

Outcomes and characteristics of nonmelanoma skin cancers ... Additional retrospective data demonstrated that ruxolitinib had a hazard ratio of 2.69 for NMSC development.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123143515

Outcomes and characteristics of nonmelanoma skin ... Additional retrospective data demonstrated that ruxolitinib had a hazard ratio of 2.69 for NMSC development.

5. opzelurahcp.com opzelurahcp.com/atopic-dermatitis/skin-clearance-results

Skin Clearance Results | Atopic Dermatitis - Opzelura HCP Patients taking OPZELURA experienced a reduction to 1.4% mean total affected BSA by Week 52 vs. a reduction to 1.7% for those taking the vehicle-to-OPZELURA.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10866801/

Real-World Use of Ruxolitinib Cream: Safety Analysis at 1 ... Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8938906/

Long-term efficacy and safety of ruxolitinib versus best ... In the primary analysis, 66 (60%) patients randomly assigned to ruxolitinib showed haematocrit control compared with 21 (19%) patients randomly assigned to best ...

8. opzelurahcp.com opzelurahcp.com/vitiligo/adverse-event-profile

safety data through 2 years 1 - Opzelura HCP In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF ...