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

ClinicalTrials.gov processed this data on March 5, 2022. Link to the current ClinicalTrials.gov record.

Recruitment Status

TERMINATED - HAS RESULTS
 (See Contacts and Locations)
Verified March 2022 by The Cleveland Clinic, National Cancer Institute (NCI)

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 31, 2012
First Posted: February 2, 2012
Results First Posted: August 14, 2018
Last Update Posted: March 15, 2022
Last Verified: March 2022
History of Changes

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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 Disease Intervention/Treatment
  • Actinic Keratosis
  • Organ or Tissue Transplant; Complications
  • Drug: 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 DateSeptember 2011
Actual Primary Completion DateNovember 2016
Actual Study Completion DateDecember 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) [Day 7 of the study]
    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 [AK counts, over a 12-month period]
    Rate of AK clearance (Analyzed by linear mixed-effect model)

Eligibility Criteria

Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study All
Accepts Healthy Volunteers No
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 Collaborators The Cleveland Clinic, National Cancer Institute (NCI)
National Cancer Institute (NCI)
Locations
  • Cleveland Clinic | Cleveland, Ohio, United States, 44195
Investigators
  • Principal Investigator: Edward Maytin, MD, PhD, The Cleveland Clinic

More Information

Additional Relevant MeSH Terms

  • Keratosis, Actinic
  • Precancerous Conditions
  • Keratosis
  • Skin Diseases
  • Neoplasms