Immunotherapy After Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

NCT04642287 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2020P001220
• 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-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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs

  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 Outcomes (8)

• The changes in the number of SCC on treated anatomical sites in post-transplant OTRs

  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

  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

  up to 4 years 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

• 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

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

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

Also known as: Topical Calcipotriene 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: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD, Assistant Professor in Dermatology, Principal Investigator

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 24, 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: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)