Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

March 22, 2023 updated by: Shadmehr Demehri, Massachusetts General Hospital

Calcipotriol Plus 5-Flourouracil Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Massachusetts General Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63108
        • Barnes-Jewish Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Calcipotriol Only Product in Cutaneous Dose Form
Calcipotriol (Calcipotriene) is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.
Other Names:
  • Topical Calcipotriol ointment
Drug: Topical 5FU
5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.
Other Names:
  • Topical 5-fluorouracil
Placebo Comparator: 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.
Drug: Vaseline
Placebo
Other Names:
  • Petrolatum
Drug: Topical 5FU
5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.
Other Names:
  • Topical 5-fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs
Time Frame: 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.
Year 2 post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percent change in baseline number of AKs on the treated anatomical sites in OTRs.
Time Frame: 8 weeks after treatment
The percent change in baseline number of AKs on the treated anatomical sites in post-transplant OTRs quantified based on participants' medical records and photographs after transplantation in test versus control group
8 weeks after treatment
The changes in TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates and other immune factors/cells in the AK and normal skin
Time Frame: at one day after 6-day treatment and at one year post-transplant.
The changes in TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates and other immune factors/cells in the AK and normal skin in test versus control group after treatment and transplantation compared to before treatment.
at one day after 6-day treatment and at one year post-transplant.
The changes in immune infiltrate in any SCC that develops after treatment
Time Frame: for up to 4 years post-transplant
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
The changes in SCC prevention (SCC number) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs
Time Frame: at one, two and four years post-transplant.
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.
at one, two and four years post-transplant.
The changes in erythema extent and intensity scores of the treated anatomical sites
Time Frame: at one day after the completion of a 6-day treatment.
The changes in erythema extent and intensity scores of the treated anatomical sites after treatment in test versus control group. Treated skin will be evaluated for any sign of irritation including erythema, crusting or ulceration using a clinical erythema scale.
at one day after the completion of a 6-day treatment.
Number of Participants with Treatment Related Adverse Events
Time Frame: From the start of treatment until 30 days after the end of treatment, up to 2 months
Adverse events will be assessed including any local skin reactions like itching and rash.
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
Time Frame: From the start of treatment until 30 days after the end of treatment
Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group
From the start of treatment until 30 days after the end of treatment
The changes in response to treatment (AK and SCC number) between treated anatomical sites
Time Frame: at one day after treatment and one year after transplantation.
The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites
at one day after treatment and one year after transplantation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2026

Primary Completion (Anticipated)

January 1, 2029

Study Completion (Anticipated)

January 1, 2030

Study Registration Dates

First Submitted

March 30, 2020

First Submitted That Met QC Criteria

March 30, 2020

First Posted (Actual)

April 1, 2020

Study Record Updates

Last Update Posted (Actual)

March 23, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019P003401

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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