Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Keratosis, Actinic

Keratosis

Skin Neoplasms

Skin Diseases

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Fluorouracil

Immunomodulating Agents

Calcipotriene

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Participants 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.

Biopsy

Clara N. Curiel-Lewandrowski

Shadmehr Demehri

Milan Anadkat

Rajan Kulkarni

This phase IIA study evaluates the effects of calcipotriene plus 5- fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients. Precancerous skin lesions, actinic keratoses (AK), may put organ transplant recipients at higher than average risk of developing skin cancer. Topical calcipotriene is a form of vitamin D and is used to treat psoriasis and topical 5- fluorouracil is a chemotherapy agent applied to the skin. The combination of calcipotriene plus 5- fluorouracil topical cream, which activates the immune cells against cancer, may help prevent skin cancer in organ transplant recipients who have precancerous skin lesions.

PRIMARY OBJECTIVE:

I. 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 fluorouracil (5-FU) immunotherapy compared with before treatment.

SECONDARY OBJECTIVES:

I. 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.

V. 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:

I. 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.

V. 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.

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

OUTLINE:

Participants receive calcipotriene plus 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 fluorouracil cream topically BID for 6 consecutive days on study.

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

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

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.

Will be assessed after the initiation of treatment compared with the identical duration prior to therapy.

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

Will be assessed after initiation of treatment compared with before treatment.

Will be assessed after one and two courses calcipotriene plus 5-FU immunotherapy with SCCs that developed before treatment using archived tumor samples.

Will be assessed 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 organ transplant recipients (OTRs).

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.

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.

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.

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.

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.

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

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients	NCT05699603	Actinic Keratos...	Biopsy Calcipotriene Fluorouracil	18 Years -	National Cancer Institute (NCI)
Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients	NCT05699603	Actinic Keratos...	Biopsy Calcipotriene Fluorouracil	18 Years -	National Cancer Institute (NCI)

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