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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Actinic Keratosis
Organ or Tissue Transplant; Complications
Intervention Drug: 5-Fluorouracil
Enrollment 18
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Solid Organ Transplant With AKs Actinic Keratoses
Hide Arm/Group Description

Patients who underwent kidney or liver transplant within 2 years, and with at least 4 premalignant skin lesions on face, ears, scalp, forearms or dorsal hands. Patients will serve as their own control; one side of the body will be randomized to 5-FU plus PDT, and the other to PDT alone.

All patients will receive one cream, 5-Fluorouracil (5FU), and will apply it to the AKs on either the right or left side of the face/scalp (per randomization scheme), once daily for 6 d prior to PDT. The ability of AKs to produce PpIX will be measured at baseline by applying methyl-aminolevulinate (Metvixia® topical cream) to the selected AKs using a fluorescence dosimeter. Prior to Metvixia, and again 3 hours after application, surface measurements of PpIX fluorescence will be taken. Then the two largest lesions (one on the left, one on the right) will be biopsied under local anesthesia, followed by red light PDT (lasting ~8 minutes). Biopsy sites will be shielded from light with a spot bandage.

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.

All patients will receive one cream, 5-Fluorouracil (5FU), and will apply it to the AKs on either the right or left side of the face/scalp (per randomization scheme), once daily for 6 d prior to PDT. The ability of AKs to produce PpIX will be measured at baseline by applying methyl-aminolevulinate (Metvixia® topical cream) to the selected AKs using a fluorescence dosimeter. Prior to Metvixia, and again 3 hours after application, surface measurements of PpIX fluorescence will be taken. Then the two largest lesions (one on the left, one on the right) will be biopsied under local anesthesia, followed by red light PDT (lasting ~8 minutes). Biopsy sites will be shielded from light with a spot bandage.

Period Title: Overall Study
Started 4 14
Completed 4 14
Not Completed 0 0
Arm/Group Title Solid Organ Transplant With AKs Actinic Keratoses Total
Hide Arm/Group Description Patients who underwent kidney or liver transplant within 2 years, and with at least 4 premalignant skin lesions on face, ears, scalp, forearms or dorsal hands. Patients will serve as their own control; one side of the body will be randomized to 5-FU plus PDT, and the other to PDT alone. 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. Total of all reporting groups
Overall Number of Baseline Participants 4 14 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 14 participants 18 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
4
  28.6%
8
  44.4%
>=65 years
0
   0.0%
10
  71.4%
10
  55.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 14 participants 18 participants
Female
1
  25.0%
3
  21.4%
4
  22.2%
Male
3
  75.0%
11
  78.6%
14
  77.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 14 participants 18 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
4
 100.0%
14
 100.0%
18
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Accumulation of Porphyrin (PpIX)
Hide Description

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).

Time Frame Day 7 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Transplant With AKs; 5FU + PDT Transplant With AKs; PDT Only Normals With AKs; 5FU + PDT Normals With AKs; PDT Only
Hide Arm/Group Description:
Patient with solid organ transplant: half of body receiving combination therapy
Patient with solid organ transplant: half of body receiving PDT alone
Patient without any organ transplant: half of body receiving combination therapy
Patient without any organ transplant: half of body receiving PDT alone
Overall Number of Participants Analyzed 4 4 14 14
Mean (95% Confidence Interval)
Unit of Measure: Change in PpIX signal (arbitrary units)
101.8
(45.1 to 158.4)
48.0
(-2.0 to 98.0)
84.3
(60.6 to 108.0)
38.4
(15.1 to 61.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Transplant With AKs; 5FU + PDT, Transplant With AKs; PDT Only
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.007
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normals With AKs; 5FU + PDT, Normals With AKs; PDT Only
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.080
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Actinic Keratosis (AK) Clearance
Hide Description Rate of AK clearance (Analyzed by linear mixed-effect model)
Time Frame AK counts, over a 12-month period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Transplant With AKs; 5FU + PDT Transplant With AKs; PDT Only Normals With AKs; 5FU + PDT Normals With AKs; PDT Only
Hide Arm/Group Description:
Patient with solid organ transplant: half of body receiving combination therapy
Patient with solid organ transplant: half of body receiving PDT alone
Patient without any organ transplant: half of body receiving combination therapy
Patient without any organ transplant: half of body receiving PDT alone
Overall Number of Participants Analyzed 4 4 14 14
Mean (95% Confidence Interval)
Unit of Measure: CR (% reduction)
At 3 months post-PDT
76.7
(46.1 to 100)
34.6
(4.3 to 64.8)
73.4
(64.0 to 82.7)
49.5
(40.1 to 58.8)
At 6 months post-PDT
58.4
(26.3 to 90.4)
23.8
(0 to 55.8)
69.0
(55.1 to 82.9)
43.1
(29.2 to 57.0)
9 mos (see ClinCaRes2018))
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
12 mos (see ClinCaRes 2018)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
0
(0 to 0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Transplant With AKs; 5FU + PDT, Transplant With AKs; PDT Only
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normals With AKs; 5FU + PDT, Normals With AKs; PDT Only
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Solid Organ Transplant With AKs Actinic Keratoses
Hide Arm/Group Description 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 with at least 4 actinic keratoses on the face, ears, scalp, forearms and/or dorsal hands.
All-Cause Mortality
Solid Organ Transplant With AKs Actinic Keratoses
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Solid Organ Transplant With AKs Actinic Keratoses
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/4 (25.00%)      0/14 (0.00%)    
Vascular disorders     
Stroke * [1]  1/4 (25.00%)  1 0/14 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Patient with lupus antioagulant, hospitalized for 2 transient ischemic attacks. Not thought to be related in any way to the skin photodynamic therapy.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Solid Organ Transplant With AKs Actinic Keratoses
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      0/14 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Edward Maytin
Organization: Cleveland Clinic
Phone: 216-445-6676
Responsible Party: Edward Maytin, MD, PhD, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01525329     History of Changes
Other Study ID Numbers: 09-1050
1R21CA156227-01A1 ( U.S. NIH Grant/Contract )
First Submitted: January 31, 2012
First Posted: February 2, 2012
Results First Submitted: May 1, 2017
Results First Posted: August 14, 2018
Last Update Posted: August 14, 2018