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Trial record 4 of 8 for:    maytin

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

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ClinicalTrials.gov Identifier: NCT01525329
Recruitment Status : Terminated (study drug no longer available in the United States)
First Posted : February 2, 2012
Results First Posted : August 14, 2018
Last Update Posted : August 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Maytin, MD, PhD, The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE January 31, 2012
First Posted Date  ICMJE February 2, 2012
Results First Submitted Date  ICMJE May 1, 2017
Results First Posted Date  ICMJE August 14, 2018
Last Update Posted Date August 14, 2018
Study Start Date  ICMJE September 2011
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
Accumulation of Porphyrin (PpIX) [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
Accumulation of PpIX [ Time Frame: 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).
Change History Complete list of historical versions of study NCT01525329 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
Actinic Keratosis (AK) Clearance [ Time Frame: AK counts, over a 12-month period ]
Rate of AK clearance (Analyzed by linear mixed-effect model)
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2012)
  • AK clearance [ Time Frame: At Day 14 and at 3 months post-treatment ]
    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 ]
    Rate of development of new AK at months 3, 6 9, and 12
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Therapy With 5-Fluorouracil and Photodynamic Therapy in Post-transplant Premalignant Skin Disease
Official Title  ICMJE Combination Therapy With 5-Fluorouracil and Photodynamic Therapy for the Treatment of Post-transplant Premalignant Skin Disease
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Actinic Keratosis
  • Organ or Tissue Transplant; Complications
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 5-Fluorouracil
  • 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.
    Intervention: Drug: 5-Fluorouracil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 16, 2018)
18
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2012)
40
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01525329
Other Study ID Numbers  ICMJE 09-1050
1R21CA156227-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: there is no plan to share individual participant data with other researchers.
Responsible Party Edward Maytin, MD, PhD, The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Edward Maytin, MD, PhD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP