Calcipotriol Plus 5-Flourouracil Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
All participants, care giver and investigators measuring or analyzing the experimental data will be blinded to the interventions. Tissue samples collected will be labeled with 3-digit unique IDs and de-identified before studying in PI's lab. The study investigator will collect AK/skin samples and label them based on the study ID (e.g. "201") without compromising their blinded status. All the study records/photographs will be kept in a locked office or password-protected computer that is only accessible by the members of the research team.
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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).
研究组 & 干预措施
Topical Calcipotriol ointment plus 5-Fluorouracil cream
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.
干预措施: Calcipotriol Only Product in Cutaneous Dose Form (Drug)
Topical Calcipotriol ointment plus 5-Fluorouracil cream
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.
干预措施: Topical 5FU (Drug)
Topical vaseline plus 5-Fluorouracil 2.5% cream
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.
干预措施: Vaseline (Drug)
Topical vaseline plus 5-Fluorouracil 2.5% cream
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.
干预措施: Topical 5FU (Drug)
结局指标
主要结局
The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs
时间窗: Year 2 post-transplant
The changes in the percentage of participants with new SCC on treated anatomical sites quantified based on participants' medical records, photographs and pathology results after transplantation in test versus control group.
次要结局
- The changes in response to treatment (AK and SCC number) between treated anatomical sites(at one day after treatment and one year after transplantation.)
- The percent change in baseline number of AKs on the treated anatomical sites in OTRs.(8 weeks after treatment)
- Number of Participants with Treatment Related Adverse Events(From the start of treatment until 30 days after the end of treatment, up to 2 months)
- The changes in TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates and other immune factors/cells in the AK and normal skin(at one day after 6-day treatment and at one year post-transplant.)
- Number of participants with any proven rejection of the graft in OTRs(From the start of treatment until 30 days after the end of treatment)
- The changes in immune infiltrate in any SCC that develops after treatment(for up to 4 years post-transplant)
- The changes in SCC prevention (SCC number) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs(at one, two and four years post-transplant.)
- The changes in erythema extent and intensity scores of the treated anatomical sites(at one day after the completion of a 6-day treatment.)
研究者
Shadmehr Demehri
MD, PHD
Massachusetts General Hospital