Trial Outcomes & Findings for Combination Therapy With 5-Fluorouracil and Photodynamic Therapy in Post-transplant Premalignant Skin Disease (NCT NCT01525329)
NCT ID: NCT01525329
Last Updated: 2022-03-15
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
18 participants
Primary outcome timeframe
Day 7 of the study
Results posted on
2022-03-15
Participant Flow
Participant milestones
| Measure |
Solid Organ Transplant With AKs
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.
|
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.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
14
|
|
Overall Study
COMPLETED
|
4
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination Therapy With 5-Fluorouracil and Photodynamic Therapy in Post-transplant Premalignant Skin Disease
Baseline characteristics by cohort
| Measure |
Solid Organ Transplant With AKs
n=4 Participants
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.
|
Actinic Keratoses
n=14 Participants
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
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 7 of the studyThe 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).
Outcome measures
| Measure |
Transplant With AKs; 5FU + PDT
n=4 Participants
Patient with solid organ transplant: half of body receiving combination therapy
|
Transplant With AKs; PDT Only
n=4 Participants
Patient with solid organ transplant: half of body receiving PDT alone
|
Normals With AKs; 5FU + PDT
n=14 Participants
Patient without any organ transplant: half of body receiving combination therapy
|
Normals With AKs; PDT Only
n=14 Participants
Patient without any organ transplant: half of body receiving PDT alone
|
|---|---|---|---|---|
|
Accumulation of Porphyrin (PpIX)
|
101.8 Change in PpIX signal (arbitrary units)
Interval 45.1 to 158.4
|
48.0 Change in PpIX signal (arbitrary units)
Interval -2.0 to 98.0
|
84.3 Change in PpIX signal (arbitrary units)
Interval 60.6 to 108.0
|
38.4 Change in PpIX signal (arbitrary units)
Interval 15.1 to 61.6
|
SECONDARY outcome
Timeframe: AK counts, over a 12-month periodRate of AK clearance (Analyzed by linear mixed-effect model)
Outcome measures
| Measure |
Transplant With AKs; 5FU + PDT
n=4 Participants
Patient with solid organ transplant: half of body receiving combination therapy
|
Transplant With AKs; PDT Only
n=4 Participants
Patient with solid organ transplant: half of body receiving PDT alone
|
Normals With AKs; 5FU + PDT
n=14 Participants
Patient without any organ transplant: half of body receiving combination therapy
|
Normals With AKs; PDT Only
n=14 Participants
Patient without any organ transplant: half of body receiving PDT alone
|
|---|---|---|---|---|
|
Actinic Keratosis (AK) Clearance
At 3 months post-PDT
|
76.7 CR (% reduction)
Interval 46.1 to 100.0
|
34.6 CR (% reduction)
Interval 4.3 to 64.8
|
73.4 CR (% reduction)
Interval 64.0 to 82.7
|
49.5 CR (% reduction)
Interval 40.1 to 58.8
|
|
Actinic Keratosis (AK) Clearance
At 6 months post-PDT
|
58.4 CR (% reduction)
Interval 26.3 to 90.4
|
23.8 CR (% reduction)
Interval 0.0 to 55.8
|
69.0 CR (% reduction)
Interval 55.1 to 82.9
|
43.1 CR (% reduction)
Interval 29.2 to 57.0
|
|
Actinic Keratosis (AK) Clearance
9 mos (see ClinCaRes2018))
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
|
Actinic Keratosis (AK) Clearance
12 mos (see ClinCaRes 2018)
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
0 CR (% reduction)
Interval 0.0 to 0.0
|
POST_HOC outcome
Timeframe: 12 months post-PDTThe time (in months) following PDT treatment at which AK lesion counts first began to increase again. (Note: The nadir in AK lesion counts is reached at about 3 months in almost all patients).
Outcome measures
| Measure |
Transplant With AKs; 5FU + PDT
n=17 Participants
Patient with solid organ transplant: half of body receiving combination therapy
|
Transplant With AKs; PDT Only
n=17 Participants
Patient with solid organ transplant: half of body receiving PDT alone
|
Normals With AKs; 5FU + PDT
Patient without any organ transplant: half of body receiving combination therapy
|
Normals With AKs; PDT Only
Patient without any organ transplant: half of body receiving PDT alone
|
|---|---|---|---|---|
|
New AK Lesion Development
|
8.1 months
Standard Deviation 2.8
|
8.5 months
Standard Deviation 2.4
|
—
|
—
|
Adverse Events
Solid Organ Transplant With AKs
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Actinic Keratoses
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Solid Organ Transplant With AKs
n=4 participants at risk
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.
|
Actinic Keratoses
n=14 participants at risk
Patients with at least 4 actinic keratoses on the face, ears, scalp, forearms and/or dorsal hands.
|
|---|---|---|
|
Vascular disorders
Stroke
|
25.0%
1/4 • Number of events 1 • 2 years
|
0.00%
0/14 • 2 years
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place