NCT03327064

A Biomarker Evaluation Trial of UAB30 in Renal Transplant Recipients at High Risk for Non-melanoma Skin Cancer

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, double-blind, placebo-controlled biomarker study in renal transplant recipients with actinic damage and a history of basal cell carcinomas and/or cutaneous squamous cell carcinomas. There will be two arms to the study: 1) daily oral UAB30 for 28 days; and 2) daily oral placebo for 28 days. The total duration of the study is anticipated to be 5 years. The hypothesis being tested is that a significantly greater percentage of subjects randomized to oral UAB30 over a period of 28 days will achieve ≥30% reduction in biomarkers of proliferation and ≥30% increase in apoptosis biomarkers than those who receive placebo. Cyclin D1 will serve as the primary biomarker. This investigation will determine whether subjects randomized to UAB30 have an increase in all trans-retinoic acid responsive genes in the skin compared to those receiving placebo. This will include an examination of target effects of UAB30 by evaluating its effects in vivo in humans on the DNA damage response and Src signaling pathways.

Detailed description

Non-melanoma skin cancers (NMSCs), which include basal cell carcinomas (BCCs) and cutaneous squamous carcinomas (SCCs), are the most common malignancy in the U.S.; it is estimated that \>3.5 million new NMSCs this year. This represents a tremendous economic impact on the U.S. healthcare system. Most NMSC are caused by overexposure to ultraviolet radiation, and current methods for their prevention consist of recommendations for limitations to sun exposure and avoidance of indoor tanning beds, the regular application of sunscreens, and a variety of other photoprotective activities. Despite these measures, the incidence of NMSCs continues to rise. NMSCs are a particular problem for organ transplant recipients (OTRs), who must take medicines to protect against rejection of their transplanted organ. These drugs suppress the host immune response that serves to identify and eliminate mutant and neoplastic keratinocytes before they can progress to clinically apparent cancers. Recent research indicates that these drugs also augment signal transduction pathways involved in skin tumor development. NMSCs develop much more frequently in long-term recipients of renal allografts and once present, they behave more aggressively. In immunosuppressed patients, the risk of developing SCCs is 65250-fold higher than in the general population, and the risk of BCCs is 10-fold greater. The rate of SCC metastases in organ transplant recipients is 7%, which is much higher than the general population. For this reason, there has been great interest in identifying novel agents for chemoprevention, which are suitable for use by OTRs. There will be two groups to the study. Individuals, aged 18 years or older, who have had a renal transplant but are in otherwise general good health, will be given UAB30 (160 mg/day) and will be compared to individuals, aged 18 years or older, who have had a renal transplant and are in otherwise general good health who are given placebo. All participants must be at increased risk of non-melanoma skin cancer as evidenced by a history of prior squamous or basal cell skin cancer, ongoing or history of actinic keratoses, and the presence, at baseline, of at least eight actinic keratoses on the face, neck, scalp and arms. Subjects will be randomized to 28 days of: 1. UAB30 at 160 mg/day, renal transplant recipients 2. placebo renal transplant recipients At baseline screening, informed consent will be obtained and skin will be examined for potential non-melanoma skin cancers. Any lesions that are clinically suspicious for non-melanoma skin cancer will be removed per standard of care prior to administration of drug. Actinic keratoses will not be removed during the 28 day study period. Two weeks later, once any lesions clinically suspicious for non-melanoma skin cancer have been removed, renal transplant recipients will be randomized to one of the treatment arms described above. Participants will return at 28 days and 112 days for assessment. 1. At randomization and 28 days, 6mm punch biopsies, or the equivalent deep shave biopsies, will be taken for individual biomarkers from non-sun exposed skin, chronically sun exposed skin, and a pre-identified AK. The chronically sun-exposed skin to be biopsied will be no less than 1 cm from the AK to be biopsied. 2. At baseline, at 28 days and at the end of study AK lesions will be assessed and counted, employing techniques that have been validated in other studies. 3. All lesions suspicious for skin cancer will be biopsied and treated appropriately (per standard of care) throughout the study. 4. Adverse events will be assessed, including NMSC and melanoma, from signing of the informed consent through the end of the trial.

Conditions

• Non-melanoma Skin Cancer

Interventions

Type	Name	Description
DRUG	UAB30	9cUAB30 promotes homodimer and heterodimer formation with retinoic acid receptors (RARs), and was shown to inhibit breast tumor development in the N-methyl-N-nitrosourea (MNU)-induced rat mammary gland carcinoma model. The compound has also shown efficacy in rodent models of skin cancer. Dose administration will be 160mg daily for 28 days.
DRUG	Placebo	This matches the UAB30 in appearance. Frequency of dosing will be daily for 28 days.

Timeline

• Start date: 2020-10-01
• Primary completion: 2023-08-31
• Completion: 2023-08-31
• First posted: 2017-10-31
• Last updated: 2024-08-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study