Immunotherapy After Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

May 5, 2025 updated by: Shadmehr Demehri, Massachusetts General Hospital

Calcipotriol Plus 5-Fluorouracil Immunotherapy for Skin Cancer Prevention in Organ Transplant Recipients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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).

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: 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
Drug: Calcipotriol Only Product in Cutaneous Dose Form
Calcipotriene is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.
Other Names:
  • Topical Calcipotriene ointment
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs
Time Frame: 8 weeks after treatment
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
8 weeks after treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The changes in the number of SCC on treated anatomical sites in post-transplant OTRs
Time Frame: 1, 2 and 4 years after treatment
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
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
Time Frame: at one day after 6-day treatment and at one year post-treatment
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.
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
Time Frame: up to 4 years 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.
up to 4 years after 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 erythema extent and intensity scores (0-4) 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 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)
at one day after the completion of a 6-day treatment
The changes in response to treatment (AKs number) between treated anatomical sites
Time Frame: at one day after treatment and one year after treatment
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 treatment
The changes in SCC prevention (number of SCC) 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.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Shadmehr Demehri, MD/PHD, Massachusetts General Hospital

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020P001220

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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