Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

December 4, 2024 updated by: Alexander Z. Wei, MD, Columbia University

A Multi-Center Phase II Study of Ruxolitinib in Solid Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma

In this open-label, multicenter, Phase II study, the investigators propose to evaluate the efficacy of ruxolitinib, an orally administered inhibitor of JAK1/2, in solid organ transplant recipients with advanced cSCC. In a safety lead-in of 6 patients, subjects will receive ruxolitinib 15mg 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. If more than 1 DLTs are observed, another cohort of 6 patients will be treated at a dose of 10mg BID. If less than 2 DLTs are observed at the new dose of 10mg, then the study will proceed to stage I using this dose; otherwise the study will stop.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Approximately 5.4 million individuals in the United States are diagnosed with non-melanoma skin cancers (NMSC) annually, with the incidence increasing over time. Twenty-five percent are cutaneous squamous cell carcinomas (cSCC), which affect up to 1,350,000 individuals and result in up to 12,000 deaths annually in the US alone. Immunosuppressed patients are particularly vulnerable to the development of highly aggressive or catastrophic cSCC. Patients receiving immunosuppressive therapy, such as solid organ transplant recipients (SOTRs), and HIV/AIDS patients have an estimated 60 to 250-fold increased risk of cSCC development. In renal SOTRs, cSCC represents over 70% of all malignancies that develop, with an incidence up to 200 times that of the general population. Post-transplant cSCC occurs at a younger age and is more aggressive than in non-transplant cohorts, with 30% of cSCC recurring within 1 year and up to 8% of disease associated with metastasis. The median survival from diagnosis of metastasis is 3 years.5 Cemiplimab, an anti-PD1 antibody, recently became the first agent to achieve regulatory approval for the treatment of advanced cSCC; however, due to the risk of graft rejection, the role of immunological checkpoint blockade in the SOTR population is extremely limited. Thus, although surgical excision is effective for sporadic cSCC, there remains a large unmet medical need for novel strategies for treatment and/or prevention of multiply recurrent, locally advanced, and metastatic cSCC, particularly in immunosuppressed patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histopathologically confirmed diagnosis of metastatic advanced cutaneous squamous cell carcinoma.
  • History of solid-organ transplant requiring immunosuppression
  • Age ≥ 18 yrs
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Karnofsky Performance Status Scale (KPS) ≥60%, Eastern Cooperative Oncology Group (ECOG) ≤2
  • No prior Janus kinase (JAK) Inhibitor therapy
  • Adequate organ function
  • All clinically significant toxicities from prior systemic therapy must be ≤ Grade 1 (with the exception of alopecia, and peripheral neuropathy, which may be ≤ grade 2).
  • Subjects must agree to undergo tumor biopsies until biopsies have been obtained from 10 subjects (i.e., biopsies are required in at least the first 10 enrolled subjects, or until a goal of 10 study biopsies are obtained). Subjects in whom a biopsy is technically not feasible or in whom would result in unacceptable risk in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator.
  • Negative pregnancy test for women of child bearing potential
  • Ability to take oral medications

  • Adequate marrow function:

    • Absolute neutrophil count (ANC) ≥1000 /mm3
    • Platelet count ≥50,000/mm3
    • Hemoglobin ≥8.0g/dL (not requiring transfusion in the past 2 weeks)

Exclusion Criteria:

  • At least 21 days must have elapsed since the last dose of systemic chemotherapy or immunotherapy and the first dose of study drug.
  • At least 14 days must have elapsed since the last dose of radiation therapy and the first dose of study drug.
  • Patients who have previously been treated with a JAK inhibitor.
  • Patients who are receiving any other investigational agents concurrently.
  • Patients who have had recent major surgery within a minimum 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access.
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib.
  • Patients with symptomatic or growing brain metastases. Patients with brain metastases that have been treated and have remained stable for at least one month prior to initiation of study therapy are eligible.
  • Concurrent use of strong CYP3A4 or CYP3A4 substrate drugs with a narrow therapeutic range within 14 days or 5 drug half-lives, whichever is longer, before start of study drug. A list of strong CYP3A4 and 2C8 inhibitors and inducers can be found in Appendix A.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib. In addition, these patients are at increased risk of lethal infections when treated with marrow- suppressive therapy.
  • Subjects with known active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients being actively treated for a second malignancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ruxolitinib

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.
Drug: Ruxolitinib
Ruxolitinib will be administered orally twice daily during the entirety of each 28-day cycle.
Other Names:
  • JAKAVI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: within the first 24 weeks of the start of study therapy
The primary endpoint is the overall response rate as defined as the best response, confirmed at ≥4 weeks using RECIST v1.1 criteria. Responses defined as: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
within the first 24 weeks of the start of study therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to 14 months
Progression-free survival (PFS) (time alive without advanced cutaneous squamous cell carcinoma (cSCC) probabilities will be estimated
Up to 14 months
Overall Survival (OS)
Time Frame: Up to17 months
The length of time from the start of treatment that subjects with the disease are still alive.
Up to17 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Columbia University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Incyte Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alexander Wei, MD, Associate Professor of Medicine at the Columbia University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 7, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 4, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 4, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 19, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AAAT5353

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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