Calcipotriene + 5-Fluorouracil for Actinic Keratosis
Recruiting in Palo Alto (17 mi)
+4 other locations
Overseen byShadmehr Demehri
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Arizona
Must be taking: Tacrolimus, MMF
Must not be taking: Voriconazole
Disqualifiers: Organ rejection, Cancer therapy, HIV, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop your current medications. However, it mentions that participants should not be on other investigational agents and should be on a stable immunosuppressive regimen without voriconazole.
What data supports the effectiveness of the drug Calcipotriene + 5-Fluorouracil for Actinic Keratosis?
Research shows that the combination of calcipotriol and 5-fluorouracil (5-FU) is effective in treating actinic keratosis (AK), which is a skin condition that can lead to squamous cell carcinoma (a type of skin cancer). Additionally, 5-FU alone is recognized as one of the most effective treatments for AK.
12345Is the combination of Calcipotriene and 5-Fluorouracil safe for treating actinic keratosis?
The combination of Calcipotriene and 5-Fluorouracil has been studied for safety in treating actinic keratosis, with most side effects being mild to moderate, such as facial irritation. Fluorouracil alone has been shown to be safe in long-term studies, with only a small percentage of participants experiencing adverse effects beyond mild skin reactions.
16789How is the drug calcipotriene plus 5-fluorouracil unique for treating actinic keratosis?
The combination of calcipotriene and 5-fluorouracil is unique because it acts as an immunotherapy, potentially enhancing the body's immune response to treat actinic keratosis, which is a precursor to skin cancer. This combination may offer a different mechanism compared to other treatments that primarily focus on direct destruction of the lesions.
1261011Eligibility Criteria
This trial is for organ transplant recipients who've had a kidney or lung transplant at least 2 years ago, are stable, and have 4-15 visible precancerous skin lesions. Participants must be adults with good overall health and blood counts within specific ranges. Pregnant women, those with recent cancer treatments, uncontrolled illnesses, certain infections or allergies to the study drugs cannot join.Inclusion Criteria
I had a kidney or lung transplant over 2 years ago and my transplant is stable.
Your white blood cell count is between 3,000 and 12,000 per microliter.
I have 4 to 15 visible skin lesions in a specific area of my body.
+8 more
Exclusion Criteria
Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
You have HIV.
You have had allergic reactions to similar medicines like calcipotriene and 5-FU.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive calcipotriene plus 5-fluorouracil cream topically twice a day for 6 consecutive days. A second course may be administered at week 8 if AKs persist.
8 weeks
Multiple visits for treatment and skin biopsies
Follow-up
Participants are monitored for safety, effectiveness, and persistence of immune cells in AKs after treatment
6 months
Regular follow-up visits
Long-term follow-up
Assessment of long-term outcomes such as new SCC diagnosis and immune cell persistence
Up to 2 years
Participant Groups
The study tests if a cream combining calcipotriene (a vitamin D form) and chemotherapy agent 5-fluorouracil can activate immune cells against precancerous skin lesions to prevent skin cancer in organ transplant patients.
1Treatment groups
Experimental Treatment
Group I: Prevention (calcipotriene, fluorouracil)Experimental Treatment3 Interventions
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.
Calcipotriene is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Dovonex for:
- Psoriasis
🇪🇺 Approved in European Union as Daivonex for:
- Psoriasis
🇨🇦 Approved in Canada as Psorcutan for:
- Psoriasis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dana-Farber Cancer InstituteBoston, MA
Massachusetts General Hospital Cancer CenterBoston, MA
Oregon Health and Science UniversityPortland, OR
University of Arizona Cancer Center - Prevention Research ClinicTucson, AZ
More Trial Locations
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Who Is Running the Clinical Trial?
University of ArizonaLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. [2020]Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.
Real-World Experience With Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis. [2023]5-fluorouracil (5-FU) is one of the most effective topical treatments for actinic keratosis (AK). A new 4% formulation of 5-FU was recently approved in Europe.
Noninflammatory destruction of actinic keratoses by fluorouracil. [2013]Sequential topical application of fluorouracil and 0.5% triamcinolone acetonide cream is as effective in the treatment of actinic keratoses as fluorouracil alone, but the combination obviates the unpleasent irritation caused by fluorouracil. Diluted (0.1%) triamcinolone acetonide cream preparations are ineffective in the suppression of the associated inflammation. There is no detectable difference in the number of new actinic keratoses between the combination therapy and fluorouracil alone. These findings demonstrate that the degree of success with fluorouracil therapy in actinic keratosis is not related to the degree of inflammation associated with the treatment and are consistent with a chemotherapeutic explanation of fluorouracil's effect on actinic keratosis.
Sequential treatment of multiple actinic keratoses with solaraze and actikerall. [2021]Interest is increasing in the use of sequential or combined therapeutic modalities for spot or area treatment of actinic keratoses (AKs) to achieve complete sustained remission. For multiple lesions in a contained area, topical treatment offers less discomfort, better cosmesis and greater patient convenience than destructive/ablative techniques. Twelve patients with multiple grade I and II AK lesions of the scalp (cases 1-10) or the dorsum of the hand (cases 11 and 12), most with a history of recurrence, were treated with Solaraze gel (3% diclofenac sodium in 2.5% hyaluronic acid) twice daily for 12 weeks, followed by a 2-week treatment-free interval, then Actikerall cutaneous solution (5-fluorouracil 5 mg/g and salicylic acid 100 mg/g) once daily for up to 6 weeks as required. Sequential treatment provided complete (clinical and histological) clearance in 8/10 male patients. Two patients with numerous lesions had partial clearance (significant improvement) and the remaining few lesions were treated with erbium laser. Both female patients achieved complete clinical clearance with sequential treatment. Solaraze/Actikerall were well tolerated. A case of contact dermatitis with Solaraze resolved after discontinuation and the patient progressed to treatment with Actikerall. Local application site reactions resolved upon treatment completion. Topical lesion-directed sequential treatment with Solaraze/Actikerall is a rational approach to treat patients with multiple AKs. Sequential treatment produces excellent clearance rates which are accompanied by relevant improvement in patients' quality of life.
Management of psoriasis with calcipotriol used as monotherapy. [2014]The vitamin D analog calcipotriene/calcipotriol (Dovonex/Daivonex) offers advantages over other forms of topical therapy in some patients with psoriasis.
Fluorouracil cream 0.5% for actinic keratoses on multiple body sites: an 18-month open-label study. [2013]This prospective 18-month, open-label, multicenter study assessed the long-term safety and efficacy of fluorouracil cream 0.5% in 277 participants with multiple actinic keratoses (AKs) on the face/anterior scalp and other body sites. Two treatment/observation cycles were separated by 12 months. During treatment cycle 1 (TC1), all participants were treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Twelve months later, all participants were assessed for treatment cycle 2 (TC2); participants with face/anterior scalp AKs (N = 98) were re-treated with fluorouracil cream 0.5% for 4 weeks with 4-week follow-up. Only 4 participants (7.4%) experienced a treatment-related adverse event (AE) that was not an application site reaction or eye irritation. No unexpected AEs were reported; most were mild or moderate. After TC1 (week 8), the number of AK lesions was significantly reduced on the face/anterior scalp and all other treated body sites (P
Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. [2013]New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.
Topical diclofenac: new preparation. Moderate efficacy in actinic keratosis. [2013](1) Many treatments are available for actinic keratosis. The most widely used is cryotherapy. Topical application of 5% fluorouracil cream is a second-line option. (2) Marketing authorisation has been granted for a topical gel containing 3% diclofenac, a nonsteroidal antiinflammatory drug. The excipients include 2.5% hyaluronic acid. (3) Animal pharmacology studies and in vitro tests show that hyaluronic acid delays the transcutaneous uptake of diclofenac, leading to higher concentrations in the epidermis. (4) No comparative trials with fluorouracil or other drugs have been published. Five trials comparing 3% diclofenac topical gel with its excipient are available. They show that it takes at least two or three months of treatment for the lesions to disappear in one-third to one-half of patients. Indirect comparison suggests that diclofenac is less effective than fluorouracil in terms of lesion disappearance one month after the end of treatment. The subsequent risk of relapse is unknown. (5) Local adverse effects are numerous and frequent, and include contact dermatitis, skin rash, dry skin, desquamation, pruritus, local pain, and paresthesia. Adverse effects can be due to either diclofenac or to the excipient, and seem to be less intense than with topical fluorouracil. (6) Trials have shown that topical diclofenac is effective at a dose of 0.5 g of gel applied twice a day, but this precise dose is unlikely to be used as no measuring device is included in the packaging. (7) In practice, diclofenac topical gel is less effective than fluorouracil, and is only a moderately effective option when fluorouracil is poorly tolerated and when physical treatments such as cryotherapy fail.
5-fluorouracil 0.5% cream for multiple actinic or solar keratoses of the face and anterior scalp. [2013]Carac (5-fluorouracil 0.5% cream, Aventis Pharma) was approved by the US FDA in October 2000, for the treatment of multiple actinic or solar keratoses involving the face and anterior scalp. The cream should be applied in a thin film once daily to the skin where actinic keratoses (AKs) are present. When it is applied for 1, 2, or 4 weeks, it is significantly more effective than a vehicle in the management of patients with five or more AKs at pretherapy. Pooled data from the two pivotal trials (n=384) indicate that following 4 weeks of therapy the number of subjects with total AK clearance in the Carac and vehicle groups was 52.9% and 1.6% respectively (p
Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. [2020]5-Fluorouracil is a fluoropyrimidine antineoplastic medication that is used to topically treat actinic keratoses. Although local adverse effects to the drug are common and anticipated, distant skin reactions are rare and unexpected. In this case report, we describe a patient who developed seborrheic dermatitis-like eruption at a distant site after topical application of 5-fluorouracil to his arms.
One-week treatment with once-daily fluorouracil cream 0.5% in participants with actinic keratoses. [2013]Actinic keratoses (AKs) are common in fair-skinned individuals with a history of chronic and excessive sun exposure and may progress to squamous cell carcinoma (SCC). Topical fluorouracil is an effective therapeutic option for patients with AKs, but it is associated with substantial skin irritation. The efficacy and tolerability of 1-week treatment using microsponge-based fluorouracil cream 0.5% were analyzed in 356 participants with AK lesions. One-week treatment with once-daily fluorouracil cream 0.5% was significantly more effective than vehicle control in reducing AK lesions and in achieving complete clearance (P