This clinical trial aims to investigate the efficacy of Calcipotriol ointment combined with 5-FU cream in Organ Transplant Recipients (OTRs) to determine if it can stimulate the immune cells against actinic keratoses precancerous skin lesions after transplantation and prevent cutaneous squamous cell carcinoma (SCC) in long-term.
The main goal of this investigator-initiated clinical trial is to determine the efficacy of topical calcipotriol combined with 5-fluorouracil (5-FU) treatment in OTRs on immunosuppressive medications with precancerous skin lesions called actinic keratoses (AKs) and a history of non-melanoma skin cancer in order to eliminate AKs and prevent squamous cell carcinoma (SCC) development. SCC is the most common cutaneous malignancy seen after transplantation, with a 65-250fold greater incidence in organ transplant recipients (OTRs) compared to the general population. This increased risk is due to the systemic immunosuppression caused by anti-rejection medications, which are indispensable for protecting against allograft loss. Our previous findings have established the efficacy of calcipotriol in combination with 5-FU in inducing an antitumor immunity against AKs in immunocompetent patients. This SCC risk reduction is accompanied by the induction of robust T cell immunity and TRM cell formation against AKs. Calcipotriol is a FDA-approved low calcemic vitamin D analogue for the treatment of psoriasis. Topical 5-FU is a standard chemotherapy for AKs. Based on our previous findings demonstrating the synergistic impact of TSLP induction by calcipotriol in combination with the cytotoxic effects of 5-FU that leads to a robust T cell immunity against early skin carcinogenesis in immunocompetent patients, we aim to determine whether this efficacy is maintained in OTRs on immunosuppressive therapy and its effect on SCC prevention in long-term after transplantation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Calcipotriene is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.
Placebo
5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.
Massachusetts General Hospital
Boston, Massachusetts, United States
Barnes-Jewish Hospital
St Louis, Missouri, United States
The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs
The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs quantified based on participants' medical records and photographs in test versus control group
Time frame: 8 weeks after treatment
The changes in the number of SCC on treated anatomical sites in post-transplant OTRs
The changes in number of SCC on treated anatomical sites in post-transplant OTRs quantified based on participants' medical records, photographs and pathology results in test versus control group
Time frame: 1, 2 and 4 years after treatment
The changes in the magnitude of TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates in in the AK and normal skin after transplantation
The changes in the magnitude of TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates in OTRs after transplantation compared to before transplantation in test versus control group.
Time frame: at one day after 6-day treatment and at one year post-treatment
The changes in immune infiltrate (CD3+, CD4+ and CD8+ TRM cell) in any SCC that develops after treatment
The changes in immune infiltrate in any SCC that develops after calcipotriol plus 5-FU versus Vaseline plus 5-FU treatment for up to 4 years post-transplant.
Time frame: up to 4 years after treatment
Number of Participants with Treatment Related Adverse Events
Adverse events will be assessed including any local skin reactions like itching and rash
Time frame: From the start of treatment until 30 days after the end of treatment, up to 2 months
Number of participants with any proven rejection of the graft in OTRs
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Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group.
Time frame: From the start of treatment until 30 days after the end of treatment
The changes in erythema extent and intensity scores (0-4) of the treated anatomical sites
The changes in erythema extent and intensity scores of the treated anatomical sites in test versus control group in post-transplant OTRs. Treated skin will be evaluated for any sign of irritation including erythema, crusting or ulceration using a clinical erythema scale. (No erythema=0, mild erythema=1, sever erythema with minimal scaling=2, sever erythema with significant scaling=3, sever erythema with scaling, crusting, itching and burning=4)
Time frame: at one day after the completion of a 6-day treatment
The changes in response to treatment (AKs number) between treated anatomical sites
The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites
Time frame: at one day after treatment and one year after treatment
The changes in SCC prevention (number of SCC) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs
The changes in efficacy of a twice daily 6-day treatment with topical calcipotriol plus 5-FU (test) versus Vaseline plus 5-FU (control) before transplantation in preventing SCC on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs.
Time frame: at one, two and four years post-transplant.