Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients

Inclusion Criteria:

• Patients who had received a kidney or lung transplant >= 2 years before enrollmentin the study with a stable status of transplanted graft (participants must havevisited their transplant specialist within 6 months before enrolling to the study,documenting stable graft safety). The target population includes patients who are ontacrolimus and/or MMF without voriconazole as their immunosuppressive regimen.

• Presence of four to fifteen clinically typical, visible, and discrete AKs in 25 cm^2on any of the following anatomical sites: upper extremities, face, and/or scalp.

• Age of at least 18 years. Because no dosing or adverse event (AE) data are currentlyavailable on the use of calcipotriene plus 5-FU in participants <18 years of age,children and adolescents are excluded from this study but will be eligible forfuture pediatric trials, if applicable.

• Karnofsky performance status >= 60%.

• Leukocytes >= 3,000/microliter and < 12000/ microliter.

• Absolute neutrophil count >= 1,000/microliter.

• Platelets >= 100,000/microliter.

• Creatinine =< 1.5 × institutional upper limit of normal.

• Baseline respiratory requirement for lung transplant recipients:

• Respiratory rate within 12-18/min

• PO2 saturation within 90-100mmHg

• Female participants must be non-reproductive potential (i.e., post-menopausal by ahistory of age > 50 years old and no menses for >= 1 year without an alternativemedical cause; OR history of hysterectomy, history of bilateral tubal ligation, orhistory of bilateral oophorectomy) OR must have a negative urine pregnancy test. Theeffects of calcipotriene plus 5-FU on the developing human fetus at the recommendedtherapeutic dose are unknown. For this reason and because of unknown teratogeniceffect, women of childbearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for the duration of study participation. Should a woman becomepregnant or suspect she is pregnant while participating in this study, she shouldinform her study physician immediately.

• Ability and willingness to participate in the study.

Exclusion Criteria:

• OTRs with any sign of organ rejection are not eligible.

• Patients who received any systemic cancer therapy or radiation within =< 1 year (y)of study enrollment, or have a diagnosis requiring them to receive such treatment(s)are excluded.

• Patients with known dihydropyrimidine dehydrogenase deficiency (due to the higherrisk of 5-FU toxicity).

• Patients with known history of hypercalcemia or vitamin D toxicity.

• History of treatment with calcipotriene plus 5-FU within one year before enrollmentin the study.

• The treatment area is within 5 cm of an incompletely healed wound or a suspectedbasal cell or squamous cell carcinoma.

• The treatment area contained hypertrophic and hyperkeratotic lesions, cutaneoushorns, or lesions that had not responded to repeated cryotherapy.

• Participants may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical orbiological composition to calcipotriene and or 5-FU

• Uncontrolled intercurrent illness or psychiatric illness/social situations thatwould limit compliance with study requirements.

• Pregnant women are excluded from this study because there is an unknown butpotential risk for teratogenic or abortifacient effects. Also, there is unknown butpotential risk for AEs in nursing infants secondary to treatment of the mother withcalcipotriene plus 5-FU, breastfeeding should be discontinued if the mother istreated.

• Participants who are HIV-positive will be excluded from the study. There is a higherrisk of organ rejection in HIV-positive patients, and also a higher risk ofdeveloping skin cancer, related to their infection-associated immunosuppressed stateand drug-induced immunosuppression for preventing organ rejection. In addition,considering HIV's adverse effects on CD4+ T cell function and the fact that thetopical medication in this study is specifically designed to target CD4+ T cells, weplan to exclude HIV positive patients in order to avoid this confounding factor onthe primary endpoint of the study.

• Participants with known history of chronic hepatitis B, or hepatitis C will beexcluded from the study in order to avoid confounding an existing condition with animmune response to the study agents.