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| ID | Type | Description | Link |
|---|---|---|---|
| 1R21CA156227-01A1 | U.S. NIH Grant/Contract | View source |
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study drug no longer available in the United States
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Solid Organ Transplant with AKs | Experimental | 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. |
|
| Actinic Keratoses | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-Fluorouracil | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Accumulation of Porphyrin (PpIX) | 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). | Day 7 of the study |
| Measure | Description | Time Frame |
|---|---|---|
| Actinic Keratosis (AK) Clearance | Rate of AK clearance (Analyzed by linear mixed-effect model) | AK counts, over a 12-month period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Edward Maytin, MD, PhD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
there is no plan to share individual participant data with other researchers.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Accumulation of Porphyrin (PpIX) | 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). | Posted | Mean | 95% Confidence Interval | Change in PpIX signal (arbitrary units) | Day 7 of the study |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Vascular disorders | Non-systematic Assessment | Patient with lupus antioagulant, hospitalized for 2 transient ischemic attacks. Not thought to be related in any way to the skin photodynamic therapy. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Edward Maytin | Cleveland Clinic | 216-445-6676 | maytine@ccf.org |
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| ID | Term |
|---|---|
| D055623 | Keratosis, Actinic |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D007642 | Keratosis |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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|
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| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Normals With AKs; 5FU + PDT | Patient without any organ transplant: half of body receiving combination therapy |
| OG003 | Normals With AKs; PDT Only | Patient without any organ transplant: half of body receiving PDT alone |
|
|
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| Secondary | Actinic Keratosis (AK) Clearance | Rate of AK clearance (Analyzed by linear mixed-effect model) | Posted | Mean | 95% Confidence Interval | CR (% reduction) | AK counts, over a 12-month period |
|
|
|
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| Post-Hoc | New AK Lesion Development | The 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). | Posted | Mean | Standard Deviation | months | 12 months post-PDT |
|
|
|
| 1 |
| 4 |
| 0 |
| 4 |
| EG001 | Actinic Keratoses | Patients with at least 4 actinic keratoses on the face, ears, scalp, forearms and/or dorsal hands. | 0 | 14 | 0 | 14 |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006571 |
| Heterocyclic Compounds |
| At 6 months post-PDT |
|
| 9 mos (see ClinCaRes2018)) |
|
| 12 mos (see ClinCaRes 2018) |
|
| Superiority or Other (legacy) |