Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

Mass General Brigham

Status and phase: Begins enrollment in a year or more; Phase 2

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04329221

2019P003401

Details and patient eligibility

About

This clinical trial aims to investigate the efficacy of Calcipotriol ointment combined with 5-fluorouracil cream as an immunotherapy for actinic keratosis in Organ Transplant Recipients (OTRs) before transplantation and determine whether it can prevent cutaneous squamous cell carcinoma (SCC) in OTRs post-transplant.

Full description

The main goal of this investigator-initiated clinical trial is to determine the efficacy of topical calcipotriol combined with 5-flourouracil (5-FU) treatment in organ transplant candidates with precancerous skin lesions called actinic keratoses (AKs) with a history of skin cancer in order to prevent squamous cell carcinoma (SCC) development after transplantation. SCC is the most common cutaneous malignancy seen after transplantation, with a 65-250 fold 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. Previously, we have demonstrated the high efficacy of topical calcipotriol plus 5-FU immunotherapy for AKs on the face and scalp in significantly reducing the risk of SCC development within 3 years post-treatment 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 low calcemic vitamin D analogue that is FDA-approved for the treatment of psoriasis. Topical 5-FU is a chemotherapy that is the standard treatment for AKs. Our previous research demonstrates the synergistic impact of calcipotriol in combination with 5-FU on a robust T cell immunity against early skin carcinogenesis in immunocompetent patients. Therefore, we aim to determine the efficacy of this immunotherapy before transplantation in reducing the risk of SCC post-transplant despite the immunosuppressive medications.

Enrollment: 62 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Solid organ transplant candidates with AKs and a history of non-melanoma skin cancer. The target population includes the patients who are undergoing kidney, lung, liver and heart transplantations.
• 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: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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62 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: Vaseline

Drug: Topical 5FU