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

NCT01525329 | Terminated Phase 3 Results DMC

• 2 other identifiers: 09-10501R21CA156227-01A1
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Actinic Keratosis; Organ or Tissue Transplant; Complications

Keywords

Actinic Keratosis; Photodynamic Therapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Actinic Keratosis (AK) Clearance

  AK counts, over a 12-month period

Study Arms (2)

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.

Drug: 5-Fluorouracil

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.

Drug: 5-Fluorouracil

Interventions

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.

Also known as: Fluorouracil Cream, USP 5%, 5-FU

Actinic Keratoses; Solid Organ Transplant with AKs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Cleveland Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Edward Maytin
• Organization: Cleveland Clinic

maytine@ccf.org

216-445-6676

Study Officials

• Edward Maytin, MD, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Head, Molecular Dermatology; Chairman, Dermatology Research Committee

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 2, 2012
• Study Start: September 1, 2011
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 15, 2022
• Results First Posted: August 14, 2018

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)