Cutaneous Squamous Cell CarcinomaPhase 2NCT04329221
Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients
A Phase 2 study testing Calcipotriol Only Product in Cutaneous Dose Form, Vaseline and Topical 5FU in people with Cutaneous Squamous Cell Carcinoma and Actinic Keratoses, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Cutaneous Squamous Cell Carcinoma, Actinic Keratoses, Skin Cancer
- What is being tested?
- Calcipotriol Only Product in Cutaneous Dose Form, Vaseline and Topical 5FU
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2026to Jan 2030
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02215
Barnes-Jewish Hospital
St Louis, Missouri, 63108
About this study
Official title: 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.
Read the 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.
- Conditions
- Cutaneous Squamous Cell Carcinoma, Actinic Keratoses, Skin Cancer, Organ Transplant Recipients, Immunotherapy
- Being tested
- Calcipotriol Only Product in Cutaneous Dose Form, Vaseline, Topical 5FU
- Keywords
- Calcipotriol ointment, 5-FU cream, Squamous Cell Carcinoma, Actinic Keratoses, Organ Transplant Recipients, Prevention, Immunotherapy
- Medical subject headings
- Keratosis, Actinic, Skin Neoplasms, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calcipotriol Only Product in Cutaneous Dose FormDrug
Also called Topical Calcipotriol ointment
Calcipotriol (Calcipotriene) is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.
VaselineDrug
Also called Petrolatum
Placebo
Topical 5FUDrug
Also called Topical 5-fluorouracil
5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vaseline; Drug: Topical 5FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Year 2 post-transplant
Secondary outcomes (8)
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
Measured: 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
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.
Measured: 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
The changes in immune infiltrate in any SCC that develops after calcipotriol plus 5-FU versus Vaseline plus 5-FU treatment
Measured: 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
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.
Measured: at one, two and four years post-transplant.
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.
Measured: at one day after the completion of a 6-day treatment.
Number of Participants with Treatment Related Adverse Events
Adverse events will be assessed including any local skin reactions like itching and rash.
Measured: 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
Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group
Measured: 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
The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites
Measured: at one day after treatment and one year after transplantation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start1 Jan 2026 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJan 2030 (estimated)
Why it stopped: The study was withdrawn due to lack of financial support.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cutaneous Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignment
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine
- Responsible party
- Principal investigator, Shadmehr Demehri, Massachusetts General Hospital
- Investigators
- Shadmehr Demehri, MD/PHD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04329221
- Sponsor's protocol ID
- 2019P003401
- Status last verified
- May 2025
- First submitted
- 30 Mar 2020
- Last updated
- 7 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27869649Rosenberg 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.
PubMed 30895944
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Calcipotriol Plus 5-Flourouracil Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients
- ClinicalTrials.gov ID
- NCT04329221
- Acronym / sponsor ID
- 2019P003401
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn due to lack of financial support.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Washington University School of Medicine
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 1 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Parallel assignment
| Arm | Type | Receives |
|---|---|---|
| Topical Calcipotriol ointment plus 5-Fluorouracil cream | Experimental | Drug: Calcipotriol Only Product in Cutaneous Dose Form, Drug: Topical 5FUTopical 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 | Placebo comparator | Drug: Vaseline, Drug: Topical 5FUTopical 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Calcipotriol Only Product in Cutaneous Dose FormAlso: Topical Calcipotriol ointmentCalcipotriol (Calcipotriene) is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin. | Drug | Topical Calcipotriol ointment plus 5-Fluorouracil cream |
| VaselineAlso: PetrolatumPlacebo | Drug | Topical vaseline plus 5-Fluorouracil 2.5% cream |
| Topical 5FUAlso: Topical 5-fluorouracil5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used. | Drug | Topical Calcipotriol ointment plus 5-Fluorouracil cream, Topical vaseline plus 5-Fluorouracil 2.5% cream |
Primary outcome
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.
8 secondary outcomes
The percent change in baseline number of AKs on the treated anatomical sites in OTRs.
Time frame: 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 immune infiltrate in any SCC that develops after treatment
Time frame: 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 erythema extent and intensity scores of the treated anatomical sites
Time frame: 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
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
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2025.
- Background: PubMed 27869649Cunningham 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.
- Background: PubMed 30895944Rosenberg 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.
- Individual participant dataSharing planned: No
Related trials for Cutaneous Squamous Cell Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingPhase 2
Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System
Locally Recurrent Skin Squamous Cell Carcinoma, Metastatic Skin Squamous Cell Carcinoma
RecruitingPhase 3
High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma, Stage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
Active, not recruitingPhase 2/3
Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shadmehr Demehri, MD/PHD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Calcipotriol Only Product in Cutaneous Dose Form, Vaseline and Topical 5FU in people with Cutaneous Squamous Cell Carcinoma and Actinic Keratoses, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The changes in the percentage of participants with new SCC on treated anatomical sites in OTRs (time frame: Year 2 post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04329221, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2025.