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Combination Therapy With 5-FU and PDT for the Treatment of Post-transplant Premalignant Skin Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Maytin, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01525329
First received: January 31, 2012
Last updated: November 15, 2016
Last verified: November 2016
  Purpose
This randomized, intra-patient comparative study is designed to investigate the combination regimen of 5-FU and PDT, versus PDT alone, for its ability to generate significantly elevated levels of the target photosensitizer, 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.

Condition Intervention Phase
Actinic Keratosis
Organ or Tissue Transplant; Complications
Drug: 5-Fluorouracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination Therapy With 5-Fluorouracil and Photodynamic Therapy for the Treatment of Post-transplant Premalignant Skin Disease

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Accumulation of PpIX [ Time Frame: Day 7 of the study ] [ Designated as safety issue: No ]

    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:
  • AK clearance [ Time Frame: At Day 14 and at 3 months post-treatment ] [ Designated as safety issue: No ]
    1) Rate of AK clearance at Day 14 (at the time of suture removal) and at 3 months

  • Development of new AKs [ Time Frame: At 3, 6, 9, and 12 months post-treatment ] [ Designated as safety issue: No ]
    Rate of development of new AK at months 3, 6 9, and 12


Estimated Enrollment: 40
Study Start Date: September 2011
Estimated Study Completion Date: November 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Other Names:
  • Fluorouracil Cream, USP 5%
  • 5-FU
Active Comparator: 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.
Other Names:
  • Fluorouracil Cream, USP 5%
  • 5-FU

Detailed Description:

This clinical trial will test a new combination of 5-fluorouracil cream (5FU) and methylaminolevate 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).

20 organ transplant recipients and 20 normal patients, with AKs on face, scalp, ears, forearms or back of the hand are enrolled 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525329

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Edward Maytin, MD, PhD The Cleveland Clinic
  More Information

Responsible Party: Edward Maytin, Section Head, Molecular Dermatology; Chairman, Dermatology Research Committee, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01525329     History of Changes
Other Study ID Numbers: 09-1050  1R21CA156227-01A1 
Study First Received: January 31, 2012
Last Updated: November 15, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No
Plan Description: there is no plan to share individual participant data with other researchers.

Keywords provided by The Cleveland Clinic:
Actinic Keratosis
Photodynamic Therapy

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms
Fluorouracil
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 06, 2016