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

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:

MedlinePlus related topics: Skin Conditions

Drug Information available for: Fluorouracil

U.S. FDA Resources

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:	December 2014
Estimated Primary Completion Date:	July 2014 (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.	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.	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

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.

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
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

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

Locations

United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Margo Riha, BSN, RN 216-445-8616 riham@ccf.org
Contact: Shilpi Khetarpal, MD khetars@ccf.org
Principal Investigator: Edward Maytin, MD, PhD
Sub-Investigator: Phillip Bailin, MD
Sub-Investigator: Titte R Srinivas, MD
Sub-Investigator: Nizar Zein, MD
Sub-Investigator: Angela Kyei, MD
Sub-Investigator: Alexandra Xhang, MD
Sub-Investigator: Rim Ishak, MD

Sponsors and Collaborators

The Cleveland Clinic

National Cancer Institute (NCI)

More Information

No publications provided

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:	February 14, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by The Cleveland Clinic:

Actinic Keratosis
Photodynamic Therapy

Additional relevant MeSH terms:

Keratosis
Keratosis, Actinic
Precancerous Conditions
Skin Diseases
Neoplasms
Fluorouracil
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 18, 2013