NCT01525329

Combination Therapy With 5-Fluorouracil and Photodynamic Therapy in Post-transplant Premalignant Skin Disease

Combination Therapy With 5-Fluorouracil and Photodynamic Therapy for the Treatment of Post-transplant Premalignant Skin Disease

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: The Cleveland Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized, intra-patient comparative study is designed to investigate the combination regimen of 5-fluorouracil cream (5FU) and Photodynamic Therapy (PDT), versus PDT alone, for its ability to generate significantly elevated levels of the target photosensitizer, protoporphyrin IX (PpIX), in lesions of actinic keratoses (AKs) and to more effectively treat and prevent recurrence of AKs. The target population comprises patients with solid organ transplants (renal, hepatic), as well as normal (immunocompetent) subjects to control for possible influences of immunosuppression.

Detailed description

This clinical trial will test a new combination of 5-fluorouracil cream (5FU) and methylaminolevulinate photodynamic therapy (MAL-PDT), versus MAL-PDT alone, as treatment for actinic keratoses (AKs) in immunosuppressed organ transplant recipients (OTRs) and an immunocompetent control group. Objectives: 1) Determine whether topical pretreatment with 5-FU selectively increases the amount of photosensitizer (PpIX) produced within AK lesions, relative to non-pretreated lesions. 2) Determine whether the combination treatment improves lesion resolution and reduces the incidence of new AKs. 3) Determine whether biomarkers in tissue and blood are predictive of patient responsiveness to 5FU (PpIX induction, new lesion incidence, and clinical toxicity). We plan to enroll 20 organ transplant recipients and 20 normal patients, with AKs on face, scalp, ears, forearms or back of the hand through Dermatology and Transplant Clinic at Cleveland Clinic. Women of childbearing age must use contraception and have a negative pregnancy test. Study participants will apply 5FU daily for 6 days; MAL/PDT is administered on 7th day. PpIX will be measured in lesions using a noninvasive dosimeter. Biopsies will be taken from selected lesions, and AKs will be photographed. Participants will be asked to complete a questionnaire to document adverse events. Patients are evaluated at day 14, and months 3, 6, 9, 12, to document AK clearance and new lesion appearance.

Conditions

• Actinic Keratosis
• Organ or Tissue Transplant; Complications

Interventions

Type	Name	Description
DRUG	5-Fluorouracil	All patients will receive one cream, 5-Fluorouracil, and will be instructed to apply the cream according to the randomization schema to AKs on either the right or left side of the face/scalp once a day for 6 days prior to PDT. A baseline measurement of the tumor's ability to produce PpIX will be done by applying methyl-aminolevulinic acid (Metvixia® topical cream) to the selected AKs and using the Aurora© dosimeter. Prior to Metvixia, and again 3 hours after application, surface measurements of the PpIX fluorescence will be taken. Then, the two largest precancer lesions (one on the left side, one on the right side) will be biopsied under local anesthesia, followed by red light PDT (lasting \~8 minutes). The biopsy sites will be shielded from the light with a circular spot bandage.

Timeline

• Start date: 2011-09-01
• Primary completion: 2016-11-01
• Completion: 2016-12-01
• First posted: 2012-02-02
• Last updated: 2022-03-15
• Results posted: 2018-08-14

Locations

1 site across 1 country: United States