Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

NCT04329221 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2019P003401
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Keywords

Calcipotriol ointment; 5-FU cream; Squamous Cell Carcinoma; Actinic Keratoses; Organ Transplant Recipients; Prevention; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs

  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 Outcomes (8)

• The percent change in baseline number of AKs on the treated anatomical sites in OTRs.

  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

  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

  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.

Study Arms (2)

Topical Calcipotriol ointment plus 5-Fluorouracil cream

EXPERIMENTAL

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; Drug: Topical 5FU

Topical vaseline plus 5-Fluorouracil 2.5% cream

PLACEBO COMPARATOR

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; Drug: Topical 5FU

Interventions

Calcipotriol Only Product in Cutaneous Dose Form DRUG

Calcipotriol (Calcipotriene) is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.

Also known as: Topical Calcipotriol ointment

Topical Calcipotriol ointment plus 5-Fluorouracil cream

Vaseline DRUG

Placebo

Also known as: Petrolatum

Topical vaseline plus 5-Fluorouracil 2.5% cream

Topical 5FU DRUG

5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.

Also known as: Topical 5-fluorouracil

Topical Calcipotriol ointment plus 5-Fluorouracil cream; Topical vaseline plus 5-Fluorouracil 2.5% cream

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Washington University School of Medicine: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63108, United States

Location

Related Publications (2)

• Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, Turkoz A, Kopan R, Schaffer A, Saavedra AP, Wallendorf M, Cornelius LA, Demehri S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017 Jan 3;127(1):106-116. doi: 10.1172/JCI89820. Epub 2016 Nov 21.

  PMID: 27869649 BACKGROUND

• Rosenberg AR, Tabacchi M, Ngo KH, Wallendorf M, Rosman IS, Cornelius LA, Demehri S. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019 Mar 21;4(6):e125476. doi: 10.1172/jci.insight.125476. eCollection 2019 Mar 21.

  PMID: 30895944 BACKGROUND

MeSH Terms

Conditions

Keratosis, Actinic; Skin Neoplasms; Carcinoma, Squamous Cell

Interventions

Petrolatum; Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Hydrocarbons; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shadmehr Demehri, MD/PHD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD

Model Details: Parallel assignment

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)