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

Recruitment Status
TERMINATED - HAS RESULTS
(See Contacts and Locations)Verified February 2022 by The Cleveland Clinic
Sponsor
The Cleveland Clinic
Information Provided by (Responsible Party)
Edward Maytin, MD, PhD
Clinicaltrials.gov Identifier
NCT01525329
Other Study ID Numbers:
09-1050
First Submitted
January 30, 2012
First Posted
February 1, 2012
Results First Posted
April 30, 2017
Last Update Posted
March 14, 2022
Last Verified
February 2022

ClinicalTrials.gov processed this data on March 2022. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Actinic KeratosisOrgan or Tissue Transplant; Complications
Drug: 5-FluorouracilDrug: 5-Fluorouracil

Study Design

Study TypeInterventional
Actual Enrollment18 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleCombination Therapy With 5-Fluorouracil and Photodynamic Therapy for the Treatment of Post-transplant Premalignant Skin Disease
Study Start DateAugust 31, 2011
Actual Primary Completion DateOctober 31, 2016
Actual Study Completion DateNovember 30, 2016

Groups and Cohorts

Group/CohortIntervention/Treatment
Solid Organ Transplant with AKs
Patients who have undergone kidney or liver transplant within 2 years and have at least 4 premalignant skin lesions on the face, ears, scalp, forearms and/or dorsal hands. Patients will serve as their own control, and one side of the body will be randomized to either 5-FU plus PDT, and the other will receive PDT alone.
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.
Actinic Keratoses
Patients with at least 4 actinic keratoses on the face, ears, scalp, forearms and/or dorsal hands. Patients will serve as their own control, and one side of the body will be randomized to either 5-FU plus PDT, and the other will receive PDT alone.
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.

Outcome Measures

Primary Outcome Measures
  1. Accumulation of Porphyrin (PpIX)
    The primary endpoint of this study will be the accumulation of PpIX at 3 h after MAL application (measured noninvasively, in each treated region). (Region refers to the half-face or half-scalp area treated with PDT monotherapy, or the contralateral area treated with the 5-FU/PDT combination regimen).
Secondary Outcome Measures
  1. Actinic Keratosis (AK) Clearance
    Rate of AK clearance (Analyzed by linear mixed-effect model)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
At least 18 years of age
At least four (4) actinic keratoses, located on face, ears, scalp, forearms and/or dorsal hands. - Patients in the solid organ transplant arm of the study must have had either a kidney or liver transplant, and the transplantation surgery must have occurred at least 2 years prior to enrollment.
Exclusion Criteria
Pregnant or nursing
Currently participating in another clinical trial
Using any topical treatment for their actinic keratoses
Currently being treated for other cancers with medical or radiation therapy
Patients with a known hypersensitivity to 5-aminolevulinic acid, 5-fluorouracil or any component of the study material
Patients with a history of a photosensitivity disease, including porphyria cutanea tarda

Contacts and Locations

Sponsors and CollaboratorsThe Cleveland Clinic
Locations
Cleveland Clinic | Cleveland Ohio, United States, 44195
Investigators
Principal Investigator: Edward Maytin, MD, PhD, The Cleveland Clinic