search
Back to results

Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

Primary Purpose

Cutaneous Squamous Cell Carcinoma, Actinic Keratoses, Skin Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Calcipotriol Only Product in Cutaneous Dose Form
Vaseline
Topical 5FU
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cutaneous Squamous Cell Carcinoma focused on measuring Calcipotriol ointment, 5-FU cream, Squamous Cell Carcinoma, Actinic Keratoses, Organ Transplant Recipients, Prevention, Immunotherapy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Massachusetts General Hospital
  • Barnes-Jewish Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Topical Calcipotriol ointment plus 5-Fluorouracil cream

Topical vaseline plus 5-Fluorouracil 2.5% cream

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The percent change in baseline number of AKs on the treated anatomical sites in OTRs.
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
The changes in TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates and other immune factors/cells in the AK and normal skin
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.
The changes in immune infiltrate in any SCC that develops after treatment
The changes in immune infiltrate in any SCC that develops after calcipotriol plus 5-FU versus Vaseline plus 5-FU treatment
The changes in SCC prevention (SCC number) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs
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.
The changes in erythema extent and intensity scores of the treated anatomical sites
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.
Number of Participants with Treatment Related Adverse Events
Adverse events will be assessed including any local skin reactions like itching and rash.
Number of participants with any proven rejection of the graft in OTRs
Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group
The changes in response to treatment (AK and SCC number) between treated anatomical sites
The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites

Full Information

First Posted
March 30, 2020
Last Updated
March 22, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Washington University School of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT04329221
Brief Title
Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients
Official Title
Calcipotriol Plus 5-Flourouracil Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2026 (Anticipated)
Primary Completion Date
January 2029 (Anticipated)
Study Completion Date
January 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Topical Calcipotriol ointment plus 5-Fluorouracil cream
Arm Type
Experimental
Arm Description
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.
Arm Title
Topical vaseline plus 5-Fluorouracil 2.5% cream
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Calcipotriol Only Product in Cutaneous Dose Form
Other Intervention Name(s)
Topical Calcipotriol ointment
Intervention Description
Calcipotriol (Calcipotriene) is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.
Intervention Type
Drug
Intervention Name(s)
Vaseline
Other Intervention Name(s)
Petrolatum
Intervention Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Topical 5FU
Other Intervention Name(s)
Topical 5-fluorouracil
Intervention Description
5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.
Primary Outcome Measure Information:
Title
The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs
Description
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.
Time Frame
Year 2 post-transplant
Secondary Outcome Measure Information:
Title
The percent change in baseline number of AKs on the treated anatomical sites in OTRs.
Description
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
Time Frame
8 weeks after treatment
Title
The changes in TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates and other immune factors/cells in the AK and normal skin
Description
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.
Time Frame
at one day after 6-day treatment and at one year post-transplant.
Title
The changes in immune infiltrate in any SCC that develops after treatment
Description
The changes in immune infiltrate in any SCC that develops after calcipotriol plus 5-FU versus Vaseline plus 5-FU treatment
Time Frame
for up to 4 years post-transplant
Title
The changes in SCC prevention (SCC number) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs
Description
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.
Time Frame
at one, two and four years post-transplant.
Title
The changes in erythema extent and intensity scores of the treated anatomical sites
Description
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.
Time Frame
at one day after the completion of a 6-day treatment.
Title
Number of Participants with Treatment Related Adverse Events
Description
Adverse events will be assessed including any local skin reactions like itching and rash.
Time Frame
From the start of treatment until 30 days after the end of treatment, up to 2 months
Title
Number of participants with any proven rejection of the graft in OTRs
Description
Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group
Time Frame
From the start of treatment until 30 days after the end of treatment
Title
The changes in response to treatment (AK and SCC number) between treated anatomical sites
Description
The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites
Time Frame
at one day after treatment and one year after transplantation.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shadmehr Demehri, MD
Phone
617-643-6436
Email
sdemehri1@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Marjan Azin, MD
Phone
617-724-7897
Email
mazin@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shadmehr Demehri, MD/PHD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Milan J Anadkat, MD
Phone
314-362-2643
Email
manadkat@dom.wustl.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27869649
Citation
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.
Results Reference
background
PubMed Identifier
30895944
Citation
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.
Results Reference
background

Learn more about this trial

Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

We'll reach out to this number within 24 hrs