Ruxolitinib for the Treatment of Solid Organ Transplant Recipients with Advanced Skin Squamous Cell Cancer

Inclusion Criteria

• Histologically confirmed diagnosis of cutaneous squamous cell carcinoma (cSCC)
• Unresectable or metastatic cSCC
• History of solid-organ transplant requiring immunosuppression
• Allowable prior therapies: * A maximum of 4 prior therapies for metastatic disease are allowed
• Male or female subjects, age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of >= 3 months
• Absolute neutrophil count >= 1.5 x 10^9/L (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Platelets >= 100 x 10^9/L (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Hemoglobin >= 9 g/dL (transfusion is acceptable to meet this criteria) (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) OR calculated creatinine clearance >= 50 mL/min for subjects with creatinine levels > 1.5 x institutional ULN (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase =< 2.5 x ULN, or =< 5 x ULN in subjects with liver metastases (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Total bilirubin =< 1.5 x ULN (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support) * Note: Patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the principal investigator
• International normalized ratio (INR) or prothrombin time (PT) < 1.5 x ULN unless subject is receiving anticoagulation therapy as long as PT or INR is within therapeutic range of intended use of anticoagulant (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Activated partial thromboplastin time (aPTT) < 1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PTT is within therapeutic range of intended use of anticoagulants (within 28 days of treatment initiation and must be independent of hematopoietic growth factor support)
• Presence of baseline measurable disease by RECIST v1.1 for solid tumors, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• The effects of ruxolitinib on the developing human fetus are unknown, and thus female subjects of childbearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and are not postmenopausal [defined as >= 12 months of amenorrhea]) must have a negative pregnancy test at screening and must agree to use adequate contraception (complete abstinence, or two methods of birth control prior to study entry and until at least 4 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Fertile men must also agree to use adequate contraception (2 barrier methods or abstinence) during the study and for up to 4 months after the last dose of study drug
• Subjects must agree to pre- and on-treatment tumor biopsies. Subjects in whom 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. Use of outside archived tumor tissue for a baseline biopsy is not permitted
• Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

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
• Human immunodeficiency virus (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