Immunotherapy After Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

Mass General Brigham

Status and phase: Withdrawn; Phase 2

Conditions: Cutaneous Squamous Cell Carcinoma; Immunotherapy; Skin Cancer; Actinic Keratoses; Organ Transplant Recipients

Treatments: Drug: Vaseline; Drug: Topical 5FU; Drug: Calcipotriol Only Product in Cutaneous Dose Form

Study type: Interventional

Funder types: Other

Identifiers

NCT04642287

2020P001220

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 50+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Solid organ transplant recipients with AKs and a history of non-melanoma skin cancer in one year prior to enrollment into the study. The target population includes post-transplant OTRs.
• Presence of four to fifteen clinically typical, visible, and discrete AKs in 25 cm2 on any of the four anatomical sites: scalp, face, right upper extremity and left upper extremity.
• The period between the first visit and transplantation is minimum 4 weeks and maximum 12 months.
• Age of at least 18 years
• Ability and willingness of the patient to participate in the study (Informed consent will be obtained)

Exclusion criteria

• Treatment area is within 5 cm of an incompletely healed wound or a suspected basal cell or squamous cell carcinoma.
• Treatment area contained hypertrophic and hyperkeratotic lesions, cutaneous horns, or lesions that had not responded to repeated cryotherapy.
• Patients with history of hypercalcemia or vitamin D toxicity.
• Female participants must be either of non-reproductive potential (i.e., post-menopausal by history of age > 50 years old and no menses for >1 year without an alternative medical cause; OR history of hysterectomy, history of bilateral tubal ligation, or history of bilateral oophorectomy) OR must have a negative serum pregnancy test within 7 days prior to study registration.
• Patients with DPD (Dihydropyrimidine Dehydrogenase) deficiency (due to their higher risk of 5-FU toxicity).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Topical Calcipotriol ointment plus 5-Fluorouracil cream

Experimental group

Description:

Topical Calcipotriol 0.0025% ointment plus 5-Fluorouracil 2.5% cream will be administered by the participants to their face, scalp and upper extremities twice a day for 6 consecutive days.

Treatment:

Drug: Calcipotriol Only Product in Cutaneous Dose Form

Drug: Topical 5FU

Topical vaseline plus 5-Fluorouracil 2.5% cream

Placebo Comparator group

Description:

Topical Vaseline plus 5-Fluorouracil 2.5% cream will be administered by the participants to their face, scalp and upper extremities twice a day for 6 consecutive days.

Treatment:

Drug: Topical 5FU

Drug: Vaseline