Trial Title:
Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients
NCT ID:
NCT05699603
Condition:
Actinic Keratosis
Conditions: Official terms:
Keratosis, Actinic
Keratosis
Fluorouracil
Calcipotriene
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo skin biopsy
Arm group label:
Prevention (calcipotriene, fluorouracil)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Drug
Intervention name:
Calcipotriene
Description:
Applied topically
Arm group label:
Prevention (calcipotriene, fluorouracil)
Other name:
Calcipotriol
Other name:
Dovonex
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Applied topically
Arm group label:
Prevention (calcipotriene, fluorouracil)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Arizona Cancer Center - Prevention Research Clinic
Address:
City:
Tucson
Zip:
85719
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clara N. Curiel-Lewandrowski
Phone:
520-694-7236
Email:
ccuriel@email.arizona.edu
Investigator:
Last name:
Clara N. Curiel-Lewandrowski
Email:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital Cancer Center
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shadmehr Demehri
Phone:
617-643-6436
Email:
sdemehri1@mgh.harvard.edu
Investigator:
Last name:
Shadmehr Demehri
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Milan Anadkat
Phone:
314-362-2643
Email:
manadkat@wustl.edu
Investigator:
Last name:
Milan Anadkat
Email:
Principal Investigator
Facility:
Name:
Oregon Health and Science University
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rajan Kulkarni
Phone:
971-808-7087
Email:
kulkarnr@ohsu.edu
Investigator:
Last name:
Rajan Kulkarni
Email:
Principal Investigator
Start date:
July 2, 2024
Completion date:
February 1, 2029
Lead sponsor:
Agency:
University of Arizona
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of Arizona
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05699603