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Actinic KeratosisPhase 2NCT05699603

Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients

A Phase 2 study testing Biopsy, Calcipotriene and Fluorouracil in people with Actinic Keratosis, run by University of Arizona at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase IIA study evaluates the effects of calcipotriene plus 5- fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients. Solid organ transplant recipients are at high risk of developing skin cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Actinic Keratosis
What is being tested?
Biopsy, Calcipotriene and Fluorouracil
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
4 sitesUnited States
Study dates
2 Jul 2024to 1 Feb 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who had received a kidney or lung transplant >= 2 years before enrollment in the study with a stable status of transplanted graft (participants must have visited their transplant specialist within 6 months before enrolling to the study, documenting stable graft safety). The target population includes patients who are on tacrolimus and/or MMF without voriconazole as their immunosuppressive regimen.
  • Presence of four to fifteen clinically typical, visible, and discrete AKs in 25 cm^2 on any of the following anatomical sites: upper extremities, face, and/or scalp.
  • Age of at least 18 years. Because no dosing or adverse event (AE) data are currently available on the use of calcipotriene plus 5-FU in participants <18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable.
  • Karnofsky performance status >= 60%.
  • Leukocytes >= 3,000/microliter and < 12000/ microliter.
  • Absolute neutrophil count >= 1,000/microliter.
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  • Platelets >= 100,000/microliter.
  • Creatinine =< 1.5 × institutional upper limit of normal.
  • Baseline respiratory requirement for lung transplant recipients:
  • Respiratory rate within 12-18/min
  • PO2 saturation within 90-100mmHg
  • Female participants must be non-reproductive potential (i.e., post-menopausal by a 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 urine pregnancy test. The effects of calcipotriene plus 5-FU on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because of unknown teratogenic effect, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
  • Ability and willingness to participate in the study.

Who cannot join

  • OTRs with any sign of organ rejection are not eligible.
  • Patients who received any systemic cancer therapy or radiation within =< 1 year (y) of study enrollment, or have a diagnosis requiring them to receive such treatment(s) are excluded.
  • Patients with known dihydropyrimidine dehydrogenase deficiency (due to the higher risk of 5-FU toxicity).
  • Patients with known history of hypercalcemia or vitamin D toxicity.
  • History of treatment with calcipotriene plus 5-FU within one year before enrollment in the study.
  • The treatment area is within 5 cm of an incompletely healed wound or a suspected basal cell or squamous cell carcinoma.
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  • The treatment area contained hypertrophic and hyperkeratotic lesions, cutaneous horns, or lesions that had not responded to repeated cryotherapy.
  • Participants may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to calcipotriene and or 5-FU
  • Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because there is an unknown but potential risk for teratogenic or abortifacient effects. Also, there is unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with calcipotriene plus 5-FU, breastfeeding should be discontinued if the mother is treated.
  • Participants who are HIV-positive will be excluded from the study. There is a higher risk of organ rejection in HIV-positive patients, and also a higher risk of developing skin cancer, related to their infection-associated immunosuppressed state and drug-induced immunosuppression for preventing organ rejection. In addition, considering HIV's adverse effects on CD4+ T cell function and the fact that the topical medication in this study is specifically designed to target CD4+ T cells, we plan to exclude HIV positive patients in order to avoid this confounding factor on the primary endpoint of the study.
  • Participants with known history of chronic hepatitis B, or hepatitis C will be excluded from the study in order to avoid confounding an existing condition with an immune response to the study agents.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • University of Arizona Cancer Center - Prevention Research Clinic

    Tucson, Arizona, 85719

Other trials in United States

About this study

Official title: Phase IIA, Single-Arm, Open- Label, Clinical Trial of Calcipotriene Plus 5-fluorouracil Immunotherapy for Skin Cancer Prevention in Organ Transplant Recipients

This phase IIA study evaluates the effects of calcipotriene plus 5- fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients. Solid organ transplant recipients are at high risk of developing skin cancer. Actinic keratosis (AK), is a premalignant skin lesion that can progress to squamous cell skin cancer. In this study, solid organ transplant recipients with multiple AKs are treated with topical calcipotriene and 5-FU to evaluate how effective this therapy is against AKs and if this could lower their risk of skin cancer. Topical calcipotriene is a form of vitamin D and is used to treat psoriasis. Prior research reported immunomodulatory effects in the skin induced by topical calcipotriene. Topical 5- fluorouracil is a chemotherapy agent and is one of the therapy options for multiple AKs in specific clinical scenarios. Prior research indicates that topical calcipotriene used together with topical 5-FU was more effective in treating multiple AKs than 5-FU alone in individuals with healthy immune system. This study is investigating now if similar beneficial effects can be seen in immunosuppressed individuals who are solid organ transplant recipients.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the induction of CD4+ TRM cells (CD3+CD4+CD103+) in the actinic keratosis at one day after completing one and two courses of calcipotriene plus 5-fluorouracil (5-FU) immunotherapy compared with before treatment.

SECONDARY OBJECTIVES:

  1. To evaluate the persistence of CD4+ TRM (CD3+CD4+CD103+) in the AK at 6 months after initiation of treatment compared with before treatment.

II. To evaluate the persistence of CD4+ TRM (CD3+CD4+CD103+) in the AK at 6 months after initiation of treatment compared with after completing one and two courses of treatment.

III. To determine the percent reduction in the number of AKs on the treated areas at 8 weeks after one and two courses of calcipotriene plus 5-FU immunotherapy compared with before treatment.

IV. To determine the erythema extent and intensity scores of the treated anatomical sites at one day after the completion of one and two courses of calcipotriene plus 5-FU immunotherapy.

  1. To determine differences in AK clearance between the treated anatomical sites (upper extremities versus [vs.] face vs. scalp).

VI. To assess the safety and tolerability of one and two courses of calcipotriene plus 5-FU treatment.

VII. To assess any incidence of biopsy-proven acute organ rejection of the graft.

EXPLORATORY OBJECTIVES:

  1. To determine the percentage of participants with a new diagnosis of squamous cell carcinoma (SCC) on the treated anatomical sites at 6 months after the initiation of treatment compared with the identical duration prior to therapy.

II. To evaluate the persistence of CD4+ TRM (CD3+CD4+CD103+) in the AK at 8 weeks after treatment with one and two courses of calcipotriene plus 5-FU compared with before treatment.

III. To evaluate the induction of TSLP, CD8+ TRM and natural killer (NK) cell infiltrates in the AK at one day after one and two courses of calcipotriene plus 5-FU immunotherapy compared with before treatment.

IV. To evaluate the induction of other immune cells/factors in the AK at one day after one and two courses of calcipotriene plus 5-FU immunotherapy compared with before treatment.

  1. To determine the induction of TSLP, CD3+ T, CD4+ T, CD8+ TRM, NK cell and other immune cells/factors in the AK at one day after two courses compared with one day after one course of calcipotriene plus 5-FU immunotherapy.

VI. To evaluate the persistence of CD8+ TRM, NK cells in the AK at 8 weeks after treatment with one and two courses of calcipotriene plus 5-FU compared with before treatment.

VII. To evaluate the persistence of CD8+ TRM, NK cells in the AK at 6 months after initiation of treatment compared with before treatment. VIII. To compare the immune infiltrate in any SCC that develops over 6 months after one and two courses calcipotriene plus 5-FU immunotherapy with SCCs that developed before treatment using archived tumor samples.

IX. To evaluate the effect of number and type of field therapy and the number of cryotherapies after the trial, age, gender, history of immunosuppressive therapy, exposure to ionizing radiation or chemical carcinogens before and after transplantation, genetic factors (Fitzpatrick skin type I, II and III), pre-transplantation end-organ disease on SCC outcomes in OTRs.

  1. To compare the immune induction outcomes in AKs versus the normal skin samples.

OUTLINE:

Participants receive calcipotriene plus 5-fluorouracil cream topically twice a day (BID) for 6 consecutive days on study. Participants also undergo skin biopsies throughout the study. Patients who continue to experience AKs at week 8 may receive a second course of calcipotriene plus 5-fluorouracil cream topically BID for 6 consecutive days on study.

Being tested
Biopsy, Calcipotriene, Fluorouracil
Medical subject headings
Keratosis, Actinic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo skin biopsy

  • CalcipotrieneDrug

    Also called Calcipotriol, Dovonex

    Applied topically

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Applied topically

Study groups in NCT05699603
Study groupRoleWhat they receive
Prevention (calcipotriene, fluorouracil)ExperimentalParticipants receive calcipotriene plus fluorouracil cream topically BID for 6 consecutive days on study. Participants also undergo skin biopsies throughout the study. Patients who continue to experience AKs at week 8 may receive a second course of calcipotriene plus fluorouracil cream topically BID for 6 consecutive days on study.
Receives: Procedure: Biopsy; Drug: Calcipotriene; Drug: Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Induction of CD4+ TRM cells (CD3+CD4+CD103+) in the actinic keratosis

    Will be assessed at one day after completing one and two courses of calcipotriene plus 5-FU immunotherapy compared with before treatment. Paired t test will be performed to evaluate whether the changes from baseline are significantly different from 0.

    Measured: At one day after completing one and two courses of calcipotriene plus 5-FU immunotherapy

Secondary outcomes (7)

  1. Persistence of CD4+ TRM (CD3+CD4+CD103+) in the AK

    Will be assessed after initiation of treatment compared with after initiation of treatment compared with before treatment. The mean change from baseline at 8 weeks and 6 months, respectively, after one and two courses and the associated 95% CI will be reported for both AK and normal skin.

    Measured: At 6 months

  2. Persistence of CD4+ TRM (CD3+CD4+CD103+) in the AK

    Will be assessed after initiation of treatment compared with after completing one and two courses of treatment. The mean change from baseline at 8 weeks and 6 months, respectively, after one and two courses and the associated 95% CI will be reported for both AK and normal skin.

    Measured: At 6 months

  3. Percent reduction in the number of AKs

    Will be assessed on the treated areas at 8 weeks after one and two courses of calcipotriene plus 5-FU immunotherapy compared with before treatment.

    Measured: At 8 weeks

  4. Erythema extent and intensity scores of the treated anatomical sites

    Will be assessed at one day after the completion of one and two courses of calcipotriene plus 5-FU immunotherapy using the mean changes and the associated 95% CIs. The percentage of the participants with AK clearance (i.e., response to the treatment) and the exact (Clopper-Pearson) 95% CI will be reported by the treated anatomical sites.

    Measured: At one day after the completion of one and two courses

  5. Differences in AK clearance

    Will be assessed between the treated anatomical sites (upper extremities vs. face vs. scalp).

    Measured: At week 24

  6. Incidence of adverse events

    Will be assessed after of one and two courses of calcipotriene plus 5-FU treatment.

    Measured: After of one and two courses of calcipotriene plus 5-FU treatment

  7. Incidence of biopsy-proven acute organ rejection of the graft

    The exact (Clopper-Pearson) 95% CI will be reported.

    Measured: At week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2023
  2. Study start2 Jul 2024
  3. Primary completion1 Feb 2027 (estimated)
  4. Study completion1 Feb 2029 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
56 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05699603
Sponsor's protocol ID
NCI-2023-00310
Other IDs
P30CA023074, UG1CA242596, NCI-2023-00310, STUDY00002897, UAZ22-10-01
Status last verified
Sep 2025
First submitted
25 Jan 2023
Last updated
24 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Calcipotriene and Fluorouracil in people with Actinic Keratosis, run by University of Arizona at 4 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 13 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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. 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?

This study is still under way. Results are not available in the source record yet.

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?

Induction of CD4+ TRM cells (CD3+CD4+CD103+) in the actinic keratosis (time frame: At one day after completing one and two courses of calcipotriene plus 5-FU immunotherapy). 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 NCT05699603.

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 24 Sep 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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