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

NCT04807777 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAT5353
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cutaneous Squamous Cell Carcinoma

Keywords

Ruxolitinib; Solid Organ Transplant

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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 Outcomes (2)

• Progression-Free Survival (PFS)

  Up to 14 months

• Overall Survival (OS)

  Up to17 months

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

Ruxolitinib will be administered orally twice daily during the entirety of each 28-day cycle.

Also known as: JAKAVI

Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• Incyte Corporation: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Links

• Columbia University Medical Center

MeSH Terms

Interventions

ruxolitinib

Results Point of Contact

• Title: Alexander Wei, MD
• Organization: Columbia University

aw3056@cumc.columbia.edu

212-305-7115

Study Officials

• Alexander Wei, MD

  Associate Professor of Medicine at the Columbia University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medical Center

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: March 19, 2021
• Study Start: April 7, 2022
• Primary Completion: April 4, 2023
• Study Completion: October 4, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Locations

US (1)